Drugs, Health Technologies, Health Systems

Health Technology Review

Dextrose Prolotherapy for Musculoskeletal Conditions

Key Messages

What Is the Issue?

What Did We Do?

What Did We Find?

What Does This Mean?

Abbreviations

ABI

autologous blood injection

AE

adverse event

ESWT

extracorporeal shockwave therapy

HA

hyaluronic acid

HTA

health technology assessment

MMO

maximal mouth opening

PRP

platelet-rich plasma

PT

physical therapy

RCT

randomized controlled trial

ROM

range of motion

SR

systematic review

TMJ

temporomandibular joint

VAS

visual analogue scale

Research Question

What are the clinical effectiveness and safety of dextrose prolotherapy compared to any treatment not involving prolotherapy for adults with an acute or chronic musculoskeletal condition?

Context and Policy Issues

What Are Musculoskeletal Conditions?

Musculoskeletal conditions are a leading cause of chronic pain and disability among adults globally and in Canada.1 Musculoskeletal pain from these conditions can reduce quality of life and represents a substantial public health burden.1,2 Osteoarthritis, a progressive degenerative joint disease, is 1 of the most common forms of musculoskeletal conditions, affecting approximately 3.9 million people living in Canada (about 13.6% of adults aged 20 years or older).1 The prevalence of osteoarthritis increases with age.1 The knee is 1 of the most frequently affected joints, contributing substantially to functional limitations and health care utilization among individuals with osteoarthritis.3,4 In addition to osteoarthritis, other joint and periarticular conditions are common sources of musculoskeletal pain and related health care use. For example, pain related to the temporomandibular joint (TMJ) and the shoulder, such as rotator cuff tendinopathy, represents a frequent reason for primary care consultations.5,6 Plantar fasciitis, a common cause of heel pain and functional impairment, is another musculoskeletal condition often reported among adults seeking health care.7

Musculoskeletal conditions include both acute and chronic disorders that vary in duration, underlying mechanisms, and clinical management.1,2,8 Acute and chronic pain may co-occur in an individual. Acute musculoskeletal conditions — such as sprains, strains, and inflammatory injuries — typically arise from trauma or overuse and often subside with the appropriate treatment and healing of tissue.8 In contrast, chronic conditions, such as osteoarthritis, involve progressive structural joint changes and persistent pain that may last months or years and require long-term management strategies.1,2 Chronic musculoskeletal pain can substantially affect physical functioning and performance, quality of life, and participation in daily activities, contributing to substantial health care utilization and societal costs.1,2 Addressing pain in these populations remains a critical challenge and often needs a combination of pharmacologic and nonpharmacologic strategies.9,10

Pain Management for Adults With Musculoskeletal Conditions

Pain associated with musculoskeletal conditions is commonly managed using a multimodal integrated approach that combines pharmacologic and nonpharmacologic strategies.3,11 Clinical guidelines generally recommend nonpharmacologic interventions as first-line treatments, including patient education, physical therapy (PT) and exercise programs, weight management, and structured self-management programs.10 Pharmacologic treatments may include acetaminophen, nonsteroidal anti-inflammatory drugs, and topical analgesics.10 Some patients may benefit from intra-articular corticosteroid injections or other interventional procedures when conservative approaches are insufficient.10 Opioids are typically reserved for selected cases of severe pain that does not respond to other therapies due to the potential risks of opioid use and limited evidence of long-term benefit for patients with chronic noncancer pain.12

What Is Prolotherapy?

Prolotherapy is an injection-based therapy used for certain types of acute and chronic musculoskeletal pain, particularly in conditions involving ligament, tendon, or joint instability.13 The procedure involves injecting an irritant solution — most commonly hypertonic dextrose — into ligaments, tendons, or joint spaces to stimulate a localized inflammatory response.13 Although the exact physiological mechanisms are not fully understood, this response is intended to promote tissue repair, collagen deposition, and strengthening of connective tissue, which may improve joint stability and reduce pain over time.14

Prolotherapy protocols vary considerably across studies and clinical practice, including differences in the dextrose concentration used, additional solution components, injection sites, treatment frequency, and the use of imaging guidance, even when used for the same musculoskeletal conditions.13,14 For example, intra-articular dextrose prolotherapy involves injecting the dextrose solution directly into the joint space to target joint structures, such as the synovium and cartilage. In contrast, extra-articular prolotherapy involves injections into tissues surrounding the joint, such as ligaments, tendons, or entheses, to promote connective tissue repair and improve joint stability.13,14

The placebo effect can complicate the interpretation of prolotherapy studies. The act of receiving an injection — regardless of the solution — may influence an individual’s perception, expectations, and reported outcomes. In pain research, sham or saline injections have been shown to produce significant improvements in pain and function, highlighting the contribution of nonspecific effects to observed treatment responses.15 As a result, it is unclear whether reported benefits are truly due to the dextrose solution or to nonspecific effects of the injection. These factors underscore the importance of including active control or placebo arms in clinical trials to more accurately assess the true efficacy of dextrose prolotherapy.

Dextrose Prolotherapy in Canada

In Canada, dextrose prolotherapy is considered an emerging or complementary treatment for musculoskeletal conditions rather than a standard, widely recommended therapy. We found 5 rapid reviews conducted in Canada.16 One rapid review was conducted in 2014 by Canada’s Drug Agency (CADTH at the time) on the efficacy of prolotherapy for the management of musculoskeletal pain.17 Four other rapid reviews were published in 2024: 1 by the Institut national d’excellence en santé et en services sociaux (INESSS) in French18 and 3 by WorkSafeBC.19-21 These rapid reviews addressed the use of prolotherapy for a range of musculoskeletal conditions, including chronic musculoskeletal pain;18 wrist sprain or strain and repetitive strain injury;19 shoulder labral tears;20 and rotator cuff tendinopathy.21 Overall, these reports consistently concluded that evidence on the effectiveness of prolotherapy is limited, methodologically weak, and insufficient to support definitive conclusions regarding its clinical effectiveness or safety.

Why Is It Important to Do This Review?

Decision-makers remain uncertain about the clinical effectiveness and safety of dextrose prolotherapy. However, its uptake has expanded rapidly as part of efforts to improve pain and function in people with musculoskeletal conditions. There is a need to synthesize evidence from studies evaluating the clinical effectiveness and safety of prolotherapy, compared with alternative treatment approaches that do not involve prolotherapy, for people with musculoskeletal conditions.

Objectives

In response to an external request to support decision-making about dextrose prolotherapy, we prepared this Rapid Review to summarize and critically appraise available evidence regarding the clinical effectiveness and safety of dextrose prolotherapy compared to other treatment strategies for adults with acute or chronic musculoskeletal conditions.

Methods

Our initial scoping of the topic identified a comprehensive systematic review (SR) published by the US Department of Veterans Affairs in 2024 that aligned with our research question.22 This SR22 included literature from inception through February 2024. In consultation with the external requester, we set our search time frame from January 1, 2024, onward to capture any SRs published after the review produced by the US Department of Veterans Affairs. This SR22 was included and appraised in our rapid review.

An information specialist conducted a customized literature search, balancing comprehensiveness with relevance, of multiple sources and grey literature on March 23, 2026.

One reviewer screened citations and selected studies based on the inclusion criteria presented in Table 1 and critically appraised the included publications using 1 critical appraisal tool.23

Appendix 1 presents a detailed description of the methods and criteria used to select included studies.

Table 1: Selection Criteria

Criteria

Description

Population

Adults with an acute or chronic musculoskeletal condition

Intervention

Dextrose prolotherapy

Comparator

Alternative pain management interventions not involving prolotherapy (e.g., active control, placebo [e.g., saline, water, or injection without solution], other injection-based therapies [e.g., HA, PRP, ozone], PT, and exercise programs)

Outcomes

Clinical benefits and harms (e.g., pain intensity, pain-related functioning, physical performance, health-related quality of life, adverse events)

Study designs

SRs

Publication date

January 1, 2024, to March 23, 2026

HA = hyaluronic acid; PRP = platelet-rich plasma; PT = physical therapy; SR = systematic review.

Summary of Evidence

Quantity of Research Available

This report includes 5 SRs22,24-27 that met our inclusion criteria and addressed our research question. We reported on the characteristics and results of the subset of relevant studies.

Appendix 2 presents the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA)28 flow chart of the study selection.

Summary of Study Characteristics

Appendix 3 provides details about the characteristics of included publications.

Included Studies for Question 1: Clinical Effectiveness and Safety of Dextrose Prolotherapy for People With Musculoskeletal Conditions

We identified 5 SRs with meta-analysis;22,24-27 4 of them22,24,25,27 included meta-analyses that addressed this question. These 5 SRs22,24-27 included data from 119 unique primary randomized controlled trials (RCTs) and observational cohort studies relevant to this report. Considerable overlap exists among the included primary studies across SRs. As a result, the pooled effect estimates from separate reviews are based on some of the same data, although not all reviews reported the same outcomes. Appendix 6 presents a citation matrix illustrating the degree of primary study overlap.

Two SRs25,27 had searches limited to RCTs; 2 SRs22,24 included RCTs and comparative observational studies; and 1 SR26 included comparative studies. The 5 SRs22,24-27 searched for studies published from inception, with the last search date being reported as October 2025.24 The included SRs were conducted by researchers in the US,22 Palestine and the US,24 China,27 Thailand,26 and Greece.25

All SRs22,24-27 included studies with adult participants aged older than 18 years with the following conditions:

The SRs varied in the level of detail reported for their study population characteristics. All included SRs22,24-27 provided information on the age of participants from their included primary studies. Three SRs22,25,27 provided information on the sex of participants from their included primary studies; the authors did not report how sex was defined or measured. Authors of the SRs included numbers or percentages of female and/or male participants; other sexes or genders were not reported. None of the included SRs22,24-27 provided participant information for other PROGRESS-Plus criteria,29 such as place of residence, race, ethnicity, culture, language, occupation, religion, education, socioeconomic status, or social capital. Two SRs22,24 reported on the body mass index of participants from their included studies.

The study setting was described as outpatient in 1 SR.22 The setting was not reported in the other 4 SRs.24-27

The SRs also varied in the level of detail reported about the intervention. Three22,25,27 of the 5 SRs reported on the location of dextrose injections (intra-articular injections and/or periarticular or masseter injections). All SRs22,24-27 reported on the number of dextrose injection sessions, which ranged from single session to 8 sessions. All SRs22,24-27 reported on dextrose injection doses, which ranged from 5% to 50% in their included studies. Three22,24,26 out of the 5 SRs reported on the use of imaging guidance (ultrasound guided, palpation guided, landmark based, and fluoroscopy) for dextrose injection.

Interventions and comparators included:

All 5 SRs reported more than 1 outcome on the clinical effectiveness or safety of dextrose prolotherapy, including:

All SRs22,24-27 reported on outcomes at follow-up, which ranged from 1 month to 36 months.

Summary of Critical Appraisal

Appendix 4 provides additional details about the strengths and limitations of the included publications.

Included SRs

Of the included reviews, 2 SRs22,24 adequately reported relevant details across the critical appraisal domains, whereas 3 SRs25‑27 did not meet, or partially met, most of these domains. All 5 SRs22,24-27 included literature searches across multiple databases and reported search terms and time frames, but there were some concerns about risk of selection and/or reporting bias for some reviews. Methods were established before the reviews were conducted in 4 of the 5 SRs through protocol registration, reducing the risk of reporting bias.22,24,26,27 Three SRs24,26,27 lacked a grey literature search, which increased the risk of missing relevant studies not published in or inaccessible through typical bibliographic databases (i.e., nonindexed studies). Four SRs22,25-27 applied language restrictions, which may have introduced selection bias and omitted relevant data from non-English studies. All SRs22,24-27 assessed the quality and risk of bias of included primary studies using structured approaches, although the tools used varied. Four SRs22,24,25,27 used appropriate risk of bias tools, while 1 SR26 relied on methodological quality scales rather than a standard risk of bias tool. Three SRs25-27 did not adequately account for risk of bias in individual studies and its impact on pooled findings when interpreting and discussing the results of the SR. The 4 SRs22,24,25,27 that conducted meta-analyses relevant to the present review used appropriate statistical methods (e.g., I2 statistic). Assessment and discussion of publication bias were limited in several SRs; 1 SR24 consistently assessed publication bias with formal methods and discussed its likely impact, whereas 2 SRs22,25 partially assessed publication bias or discussed its impact on results. Two SRs26,27 did not provide any information on or discussion of publication bias. Finally, 3 SRs25-27 did not provide a list of excluded studies or justify the exclusions, while the other 2 SRs did.22,24

Two of the included SRs22,24 adequately reported relevant details across the noncritical appraisal domains, whereas 3 SRs25-27 did not meet, or only partially met, many of these domains. The authors of all 5 SRs22,24-27 defined their objectives and eligibility criteria. They also included flow charts illustrating study selection, along with reasons for excluding studies at abstract and full-text levels.22,24-27 Information about the population, intervention, comparator, and outcomes was reported in sufficient detail in 4 SRs.22,24,25,27 Although study designs were specified in all 5 SRs,22,24-27 2 SRs26,27 did not clearly justify their inclusion criteria. Most SRs used a satisfactory technique for data extraction. In all 5 SRs,22,24-27 at least 2 independent reviewers conducted the study selection and data extraction (in 4 SRs).22,24,25,27In 1 SR,26 data extraction procedures were not clearly described as duplicate, raising potential concerns about accuracy. The authors of 4 SRs22,24-26 explored heterogeneity and provided satisfactory explanation for any heterogeneity observed in the results of the review. All SRs22,24-27 reported conflicts of interest and funding sources for the review. Finally, 3 SRs25-27 did not report funding sources for the included primary studies, while the other 2 SRs did.22,24

Summary of Findings

Appendix 5 presents additional details regarding the main study findings.

Clinical Effectiveness and Safety of Dextrose Prolotherapy for Adults With Musculoskeletal Conditions

Evidence regarding the clinical effectiveness and safety of dextrose prolotherapy for adults with musculoskeletal conditions was available from 5 SRs,22,24-27 and 4 of them22,24,25,27 had meta-analyses relevant to the present review. There was considerable overlap in the primary studies included in these SRs; the pooled estimates from separate reviews thus contain much of the same data (refer to Appendix 6 for details regarding overlap). These SRs and their included primary studies reported results on various types of acute or chronic musculoskeletal pain, including knee osteoarthritis and other knee pain, shoulder and elbow pain, plantar fasciitis and other foot pain, chronic low back pain, TMJ dysfunction and pain, and other pain conditions. In general, dextrose prolotherapy appeared to be more effective in improving certain conditions, such as TMJ pain and disorders, while evidence for other pain conditions and indications remains mixed or uncertain. AEs associated with dextrose prolotherapy were generally infrequent and described as mild and transient.

Knee Osteoarthritis and Other Knee Pain

One SR22 evaluated the effectiveness and safety of dextrose prolotherapy versus comparators on knee osteoarthritis and other knee pain. Evidence for the effectiveness of dextrose prolotherapy versus placebo or other comparators was uncertain or inconclusive, with studies reporting mixed findings and no consistent pattern of benefit.

Knee Osteoarthritis: Dextrose Prolotherapy Versus Placebo

One SR22 that included 5 relevant RCTs compared dextrose prolotherapy with normal saline or water injection (Table 8).

Knee Osteoarthritis: Dextrose Prolotherapy Versus Other Comparators

One SR22 that included 5 meta-analyses and 8 RCTs compared dextrose prolotherapy with other comparators (Table 9).

Plantar Fasciitis and Other Foot Pain

Two SRs22,24 evaluated the effectiveness and safety of dextrose prolotherapy versus comparators for plantar fasciitis and other foot pain. Dextrose prolotherapy may improve pain-related functioning (foot function) and pain intensity compared with normal saline injections and PT. The evidence on the effectiveness of dextrose prolotherapy versus extracorporeal shockwave therapy (ESWT), phonophoresis, or PRP showed no statistically significant differences between groups in assessed outcomes. Patients who received corticosteroid injections had better outcomes compared to those who received dextrose prolotherapy in terms of pain intensity or severity, pain-related function, and physical performance at short-term follow-up. The efficacy of these interventions became similar in the medium-term follow-up, and dextrose prolotherapy outperformed corticosteroid injections in terms of physical performance (i.e., pain while walking).

Plantar Fasciitis: Dextrose Prolotherapy Versus Placebo

Two relevant RCTs from 1 SR22 compared dextrose prolotherapy with normal saline (Table 10).

Plantar Fasciitis: Dextrose Prolotherapy Versus Other Comparators

One SR24 that included 10 meta-analyses and 1 SR22 that included 5 relevant RCTs compared dextrose prolotherapy with other comparators (Table 11).

Shoulder Pain

Two SRs22,26 evaluated the effectiveness and safety of dextrose prolotherapy versus comparators on shoulder pain, including varied rotator cuff pathology and subacromial bursitis. Evidence for the effectiveness of dextrose prolotherapy versus placebo (normal saline injections), PT, or corticosteroid injections was uncertain or inconclusive, with studies reporting mixed findings and no consistent pattern of benefit.

Shoulder Pain (Rotator Cuff Pathology and Subacromial Bursitis): Dextrose Prolotherapy Versus Placebo

One SR22 that included 4 meta-analyses and 1 relevant RCT compared dextrose prolotherapy with normal saline (Table 12).

Shoulder Pain (Rotator Cuff Pathology and Subacromial Bursitis): Dextrose Prolotherapy Versus Other Comparators

One SR22 that included 4 meta-analyses and 3 relevant RCTs and 1 SR26 that included 1 relevant RCT compared dextrose prolotherapy with other comparators (Table 13).

Shoulder Pain (Supraspinatus Tendinopathy Only): Dextrose Prolotherapy Versus Placebo or Other Comparators

One SR22 that included 4 relevant RCTs evaluated dextrose prolotherapy versus placebo or other comparators for shoulder pain due to supraspinatus tendinopathy (Table 14).

Elbow Pain

One SR22 that included 11 RCTs evaluated the effectiveness and safety of dextrose prolotherapy versus comparators for lateral elbow tendinopathy. Dextrose prolotherapy compared with normal saline injection may improve pain-related functioning but had little to no benefit for physical performance and pain intensity. Dextrose prolotherapy compared to corticosteroid injections and ESWT provided mixed and inconclusive findings. Dextrose prolotherapy compared to HA injection or PT showed no statistically significant differences between groups in assessed outcomes. Receiving dextrose prolotherapy compared to being on a wait-list was associated with greater improvement in pain-related functioning and physical performance over 4 months.

Elbow Pain: Dextrose Prolotherapy Versus Placebo

One SR22 that included 3 relevant RCTs compared dextrose prolotherapy with normal saline (Table 15).

Elbow Pain: Dextrose Prolotherapy Versus Other Comparators

One SR22 that included 8 relevant RCTs compared dextrose prolotherapy with other comparators (Table 16).

Chronic Low Back Pain

One SR22 that included 6 relevant RCTs and 2 relevant observational cohort studies evaluated the effectiveness and safety of dextrose prolotherapy versus comparators on low back pain. The evidence for the effectiveness of dextrose prolotherapy versus normal saline or corticosteroid injections was uncertain or inconclusive, with studies reporting mixed findings and no consistent pattern of benefit.

Low Back Pain: Dextrose Prolotherapy Versus Placebo

One SR22 that included 4 relevant RCTs compared dextrose prolotherapy with normal saline (Table 17).

Low Back Pain: Dextrose Prolotherapy Versus Other Comparators

One SR22 that included 2 relevant RCTs and 2 relevant observational cohort studies compared dextrose prolotherapy with other comparators (Table 18).

TMJ Dysfunction and Pain

Three SRs22,25,27 that included 8 meta-analyses and 1 SR22 that included 4 relevant RCTs and 1 relevant observational cohort study evaluated the effectiveness and safety of dextrose prolotherapy versus comparators on TMJ dysfunction and pain. Dextrose prolotherapy may improve pain-related functioning, physical performance, and pain intensity compared to normal saline injections. Dextrose prolotherapy may improve pain intensity compared to autologous blood injection (ABI) but comparisons related to physical performance showed no between-group differences or inconclusive results. Dextrose prolotherapy showed better performance across many included outcomes compared to other comparators (e.g., low-level laser therapy, occlusal splints).

TMJ: Dextrose Prolotherapy Versus Placebo

Three SRs22,25,27 that included 5 meta-analyses and 1 SR22 that included 2 relevant RCTs compared dextrose prolotherapy with placebo (Table 19).

TMJ: Dextrose Prolotherapy Versus Other Comparators

Three SRs22,25,27 that included 3 meta-analyses and 1 SR22 that included 3 relevant RCTs and 1 relevant observational cohort study compared dextrose prolotherapy with other comparators (Table 20).

Other Pain Conditions

One SR22 that included 8 relevant RCTs and 4 relevant observational cohorts evaluated the effectiveness and safety of dextrose prolotherapy versus comparators for a range of other pain conditions (Table 21).

Non-Arthritis Knee Pain

One SR22 that included 2 relevant RCTs and 1 relevant observational cohort study compared dextrose prolotherapy with comparators for non-arthritis knee pain.

Other Types of Foot Pain (Not Plantar Fasciitis)

One SR22 that included 2 relevant RCTs and 1 relevant observational cohort study compared dextrose prolotherapy with comparators for other types of foot pain.

Hand Pain Conditions

One SR22 that included 3 relevant RCTs compared dextrose prolotherapy with comparators for hand pain conditions.

Other Conditions

One SR22 that included 1 relevant RCT and 2 relevant observational cohort studies compared dextrose prolotherapy with comparators for other conditions.

Adverse Events

Two SRs22,24 reported on AEs associated with dextrose prolotherapy. Across the 2 SRs,22,24 reported AEs associated with dextrose prolotherapy were generally infrequent and described as mild and transient (e.g., postinjection pain, swelling, bruising, or temporary discomfort).

Both SRs22,24 noted that AE reporting was inconsistent, many included studies had small sample sizes, and follow-up periods were often short, limiting the ability to detect uncommon, delayed, or longer-term harms.

Limitations

Evidence Gaps

Despite the findings from the included SRs,22,24-27 important evidence gaps remain. Additional studies with larger sample sizes are needed, as the current evidence is based on small sample sizes and limited numbers of studies per condition,22 with some SRs24,27 relying on fewer than 10 RCTs. There is also a need for greater standardization in intervention protocols (e.g., dextrose concentration, injection technique, number of sessions, and cointerventions) and outcome measurement (e.g., pain scores, functional indices), as well as more consistent reporting of follow-up time points to improve comparability across studies.

High-quality evidence beyond pain outcomes is needed, particularly for quality of life and AEs.22 In addition, studies assessing long-term outcomes are lacking.24 There is also a need for clearer and more consistent reporting of AEs. Overall, more high-quality research is needed to strengthen the evidence base and improve confidence in conclusions about effectiveness and safety across conditions.

Generalizability

The generalizability of findings is limited by variability in study populations, settings, and intervention characteristics. The potential generalizability of these findings to clinical practice in Canada should be interpreted with these limitations considered.

With respect to study populations, most primary studies included in SRs were conducted outside Canada and North America. Participant characteristics were often limited to narrowly defined clinical groups with insufficient reporting on comorbidities, disease severity, or prior treatment history.22 This may limit applicability to people living in Canada, particularly older adults, individuals with multiple chronic conditions, rural populations, and those from diverse cultural or socioeconomic backgrounds.

Prolotherapy protocols varied substantially across studies in terms of dextrose concentration, injection location, number of treatment sessions, treatment duration, and use of imaging guidance.22,24-27 Such variability makes it difficult to determine which protocols are most effective and relevant to practice settings in Canada, where provider expertise, scope of practice, and access to ultrasound-guided procedures may differ across provinces and territories.

Four22,25-27 out of the 5 SRs22,24-27 included primary studies that used a wide range of treatment comparators, including placebo or saline injections, corticosteroid injections, PT, exercise programs, PRP, and other modalities. These comparators may not consistently reflect current standards of care in Canada, referral pathways, or publicly funded treatment options, which could affect the relevance of comparative findings across patient groups and care settings. Clinical heterogeneity across conditions, including knee osteoarthritis, TMJ, plantar fasciitis, and rotator cuff tendinopathy, further limits generalizability.

Many studies focused on pain scores or functional measures (e.g., ROM), while other outcomes (e.g., time to return to work, long-term quality of life, reduction in analgesic or opioid use, avoidance of surgery, and health service utilization) were infrequently reported.22 Most studies used only short-term to medium-term follow-up periods,22,24 limiting any understanding of sustained effectiveness for chronic musculoskeletal conditions.

The quality and quantity of the evidence further influence generalizability. Several reviews noted small sample sizes, few studies per condition, and frequent methodological limitations, including risk of bias and heterogeneity in interventions and outcome measurement.22 Given the large number of outcomes and time points assessed, there is an increased likelihood of observing statistically significant findings by chance, particularly for subjective measures (e.g., pain intensity). These limitations reduce confidence in the validity, consistency, and generalizability of the observed effects.

Placebo and Nonspecific Injection Effects

The placebo effect could obscure any true impact of prolotherapy on patient outcomes. Injection therapies for musculoskeletal pain conditions are known to have a large placebo effect that complicates rigorous evaluation. One SR22 noted that injection-based interventions may be susceptible to substantial placebo and contextual effects, making it difficult to determine whether observed benefits are attributable specifically to dextrose prolotherapy, needle-related tissue stimulation, natural symptom fluctuation, or other nonspecific treatment effects. Three SRs25-27 focused more on comparative results and meta-analysis outcomes without adequately considering the impact of possible placebo effects. However, they compared prolotherapy with placebo or saline injections, which implicitly acknowledges the need to control for injection-related placebo effects.

Patients’ conditions may also improve because of factors beyond the injected therapy itself. Other factors include natural healing processes in many musculoskeletal conditions, lifestyle changes, or other cointerventions.22 It also noteworthy that maintaining blinding can be challenging in injection studies, especially when multiple injections are given around an anatomic structure.22 In addition, the true physiologic effects of prolotherapy are not well understood, and the proposed mechanisms involve a low-grade inflammatory response stimulating healing and potentially altering pain perception pathways.22

Applicability to Clinical Practice in Health Care Contexts in Canada

The applicability of the findings to clinical practice in Canada is uncertain because of the lack of studies conducted in Canada and differences in the structures of health systems, resource availability, and clinical practice patterns. Evidence on resource use, implementation requirements, and system-level effects was limited.22

There is also limited information regarding the training and expertise required to deliver prolotherapy, particularly when image-guided injections are used. In addition, substantial variation in dosing, treatment frequency, and administration protocols across studies may not align with standardized care delivery across jurisdictions in Canada.12,30 Because prolotherapy is not consistently funded or standardized across health systems, uncertainty remains regarding its feasibility, scalability, and value within publicly funded care contexts.

Equity Considerations

Equity-related data were largely absent across the included reviews. None of the SRs explicitly examined differences in access, outcomes, or acceptability across population subgroups, such as sex, socioeconomic status, geographic location, or race or ethnicity.

Limited reporting on participant demographic characteristics beyond age and sex restricts the ability to determine whether findings are applicable to populations experiencing health inequities. In addition, potential barriers to access, including provider availability, out-of-pocket costs where services are not publicly funded, and geographic disparities in service delivery, were not evaluated. The absence of evidence focused on equity limits the ability to determine whether prolotherapy may reduce or worsen disparities in access to musculoskeletal pain treatments.

Conclusions and Implications for Decision- or Policy-Making

This rapid review evaluated the literature regarding the clinical effectiveness and safety of dextrose prolotherapy compared to other alternative treatments not involving prolotherapy for adults with an acute or chronic musculoskeletal conditions. We identified 5 SRs22,24-27 that addressed the clinical effectiveness and safety of dextrose prolotherapy. The evidence summarized in this report is drawn from SRs with substantial overlap in primary studies, meaning that data from the same participants were included in more than 1 SR (refer to Appendix 6 for a citation matrix illustrating the degree of primary study overlap). As a result, some evidence may be disproportionally represented in the overall conclusions.

Summary of Evidence

Results from the 5 included SRs22,24-27 suggest that dextrose prolotherapy may provide clinical benefit for patients with some musculoskeletal conditions; however, the certainty of the evidence is generally low and findings were mixed or inconclusive across populations, comparators, and outcomes. Collectively, the reviews indicated that prolotherapy may improve pain and selected functional outcomes in patients with some conditions, but it was not consistently superior to placebo, corticosteroid injections, or other active comparators not involving prolotherapy. In several cases, any observed benefits were modest, short term, or limited to specific outcomes rather than demonstrating broad clinical superiority.

The rapid review found that evidence varied substantially by conditions and comparators. For knee osteoarthritis, evidence on the effectiveness of dextrose prolotherapy was uncertain or inconclusive, with studies reporting mixed findings and no consistent pattern of benefit.22 For plantar fasciitis, prolotherapy may improve pain-related outcomes compared with saline and PT, but corticosteroid injections appeared to provide greater short-term benefit, with differences narrowing over time.22,24 For shoulder pain and rotator cuff tendinopathy, evidence suggested that prolotherapy was not superior to normal saline injections, PT, or corticosteroid injections for most patient-reported outcomes.26 For lateral elbow tendinopathy and low back pain, the evidence was mixed, nonsignificant, or inconclusive for most assessed outcomes.22 Evidence for the effectiveness of dextrose prolotherapy on TMJ pain and disorders was somewhat more favourable, with SRs reporting reductions in pain and/or improvements in jaw mobility compared to placebo (normal saline injections) or ABI. However, these findings were based on a small number of RCTs and low-quality evidence, and comparative advantages versus botulinum toxin or other interventions were less clear.25,27 These findings suggest prolotherapy may have limited benefits for selected conditions rather than for a broader range of musculoskeletal pain conditions, although confidence remains limited.

Overall, the 5 SRs22,24-27 were generally methodologically sound, with clear objectives, multidatabase searches, study selection flow diagrams, and appropriate quality appraisal methods. Most had preregistered protocols and used duplicate review processes. Common limitations included language restrictions, limited assessment of publication bias, and insufficient consideration of how primary study bias may have influenced pooled findings.

Interpretation of the evidence is limited by important methodological concerns. Across the included SRs,22,24‑27 many of the included primary studies had small sample sizes, short follow-up durations, heterogeneous prolotherapy protocols, inconsistent outcome measures, and risk of bias concerns. These factors reduce confidence in pooled estimates and make it difficult to determine optimal dosing, treatment frequency, injection technique, or patient selection criteria.22 In several SRs, conclusions were explicitly based on low or very low certainty evidence. Therefore, even when positive findings were reported, the true effect may differ substantially from published estimates.

Two SRs22,24 reported AEs associated with dextrose prolotherapy. Although AEs were generally infrequent and mostly mild or transient, AE reporting was inconsistent, sample sizes were often small, and certainty of evidence was low to very low, limiting confidence in the overall safety profile.22,24

The findings of the current rapid review were broadly consistent with an earlier report17 by Canada’s Drug Agency (CADTH at the time) in 2014 and other rapid reviews conducted in 2024 in Canada.18-21 Similar to the previous CADTH report,17 the current rapid review found possible benefits versus some placebo (saline injections) or conservative comparators (exercise), but no consistent superiority over other treatments such as corticosteroid injections. Conclusions of the earlier CADTH report17 appeared somewhat more favourable for the use of dextrose prolotherapy in patients with low back pain or osteoarthritis, whereas the current rapid review provided a more cautious and condition-specific interpretation, likely reflecting the inclusion of newer studies, more rigorous appraisal methods, and greater attention to certainty of evidence, heterogeneity, and risk of bias. Nevertheless, both reports concluded that the evidence base remains limited, heterogeneous, and inconsistent.

Overall, the current evidence suggests that the effectiveness of dextrose prolotherapy may offer benefit for patients with selected conditions, particularly some TMJ disorders and possibly plantar fasciitis, but evidence for many common musculoskeletal conditions remains uncertain or does not demonstrate clear superiority over other treatment alternatives not involving prolotherapy. The findings are consistent with a broader understanding that musculoskeletal pain conditions are heterogeneous and that response to injectable therapies likely depends on pathology, comparator treatment, cointerventions, and patient selection. The current evidence suggests dextrose prolotherapy may represent 1 option among several nonsurgical treatments, rather than a uniformly effective intervention, with potential benefits varying by indication. Additional high-quality comparative research is needed to clarify where it may provide meaningful clinical value.

Considerations for Future Research

Future research is needed to clarify the clinical role of dextrose prolotherapy across musculoskeletal conditions, as the current evidence base is limited by small studies, heterogeneous treatment protocols, short follow-up periods, and methodological concerns.22 Well-designed RCTs with adequate statistical power and larger sample sizes are needed, particularly for conditions for which current findings are mixed or uncertain, such as knee osteoarthritis and chronic low back pain. Future studies would benefit from greater standardization and reporting of intervention characteristics, including dextrose concentration, injection technique, use of imaging guidance, number of sessions, cointerventions, and provider expertise. Consistent use of clinically relevant comparators, such as physiotherapy, corticosteroid injections, exercise therapy, and other injectable treatments, would also improve understanding of the relative value of prolotherapy in practice.

Longer-term studies are needed to determine duration of benefit, recurrence of symptoms, repeat treatment requirements, and delayed harms, as many existing studies reported only short-term or medium-term outcomes.24 Future research should also assess broader outcomes relevant to patients and health systems, including quality of life, time to return to work, analgesic or opioid use, patient satisfaction, health service utilization, and systematic reporting of AEs. Additional evidence is needed to identify patient subgroups most likely to benefit from this treatment and to evaluate cost-effectiveness, implementation requirements, and feasibility within publicly funded systems such as health systems in Canada. However, some of these outcomes may have been evaluated in studies beyond the scope of this review, as they were not the primary focus of our literature search. Studies including diverse and underserved populations would further strengthen the relevance and equity of future evidence.

Considerations for Clinical Practice or Considerations for Decision- or Policy-Making

This Rapid Review summarizes the current evidence on dextrose prolotherapy and is intended to inform, rather than provide, clinical or policy recommendations. Current evidence suggests prolotherapy may offer limited benefits for patients with selected musculoskeletal conditions, while evidence for most indications remains mixed or uncertain. These findings may support consideration of prolotherapy as a potential adjunct or alternative nonsurgical option within selected musculoskeletal or temporomandibular care pathways when clinically appropriate.

Certain considerations of the evidence base may help contextualize the findings for decision-makers, including that the available evidence was drawn largely from studies conducted outside Canada, often in specialized outpatient or research settings, and with variable patient populations, treatment protocols, and comparators.22 As a result, the extent to which reported findings apply to care settings in Canada, provincial and territorial funding models, and populations with multimorbidity, older adults, or complex chronic pain may be uncertain. The evidence also suggests that outcomes may differ by specific musculoskeletal conditions. Therefore, it may be considered whether any implementation would be condition-specific rather than assuming applicability across all pain indications.

In addition to clinical findings, accessibility of prolotherapy services — including geographic availability of trained providers, referral pathways, wait times, and whether access differs between urban, rural, and remote communities — should be considered to support equitable access. Consideration may also be given to the health care resources required to deliver prolotherapy, such as clinic capacity, procedural space, consumables, imaging equipment where ultrasound guidance is used, and the need for repeat treatment sessions. Potential effects on health care staff may include training requirements, scope of practice considerations, appointment time, and administrative support for scheduling and follow-up. Budgetary considerations may include direct treatment costs to patients where services are privately funded, opportunity costs for clinicians and facilities, and broader implications for publicly funded systems if demand increases. It is also important to consider whether access or affordability could differ for equity-deserving groups, including people living in rural or remote areas, individuals with lower incomes, and patients with mobility or transportation barriers. In the context of limited and heterogeneous evidence, these operational, financial, and equity considerations may be relevant alongside the current clinical findings when evaluating the role of dextrose prolotherapy in care pathways.

References

1.Government of Canada. Osteoarthritis in Canada: surveillance report. 2020. Accessed March 16, 2026. https://www.canada.ca/en/public-health/services/publications/diseases-conditions/osteoarthritis.html

2.Woolf AD, Pfleger B. Burden of major musculoskeletal conditions. Bull World Health Organ. 2003;81(9):646-56. PubMed

3.Gibbs AJ, Gray B, Wallis JA, et al. Recommendations for the management of hip and knee osteoarthritis: A systematic review of clinical practice guidelines. Osteoarthritis Cartilage. Oct 2023;31(10):1280-1292. doi:10.1016/j.joca.2023.05.015 PubMed

4.Zhu S, Qu W, He C. Evaluation and management of knee osteoarthritis. J Evid Based Med. Sep 2024;17(3):675-687. doi:10.1111/jebm.12627 PubMed

5.Valesan LF, Da-Cas CD, Réus JC, et al. Prevalence of temporomandibular joint disorders: a systematic review and meta-analysis. Clin Oral Investig. Feb 2021;25(2):441-453. doi:10.1007/s00784-020-03710-w PubMed

6.Leong HT, Fu SC, He X, Oh JH, Yamamoto N, Hang S. Risk factors for rotator cuff tendinopathy: A systematic review and meta-analysis. J Rehabil Med. Oct 4 2019;51(9):627-637. doi:10.2340/16501977-2598 PubMed

7.Rhim HC, Kwon J, Park J, Borg-Stein J, Tenforde AS. A Systematic Review of Systematic Reviews on the Epidemiology, Evaluation, and Treatment of Plantar Fasciitis. Life (Basel). Nov 24 2021;11(12)doi:10.3390/life11121287 PubMed

8.Orejel Bustos A, Belluscio V, Camomilla V, et al. Overuse-Related Injuries of the Musculoskeletal System: Systematic Review and Quantitative Synthesis of Injuries, Locations, Risk Factors and Assessment Techniques. Sensors (Basel). Apr 1 2021;21(7)doi:10.3390/s21072438 PubMed

9.El-Tallawy SN, Nalamasu R, Salem GI, LeQuang JAK, Pergolizzi JV, Christo PJ. Management of Musculoskeletal Pain: An Update with Emphasis on Chronic Musculoskeletal Pain. Pain Ther. Jun 2021;10(1):181-209. doi:10.1007/s40122-021-00235-2 PubMed

10.Babatunde OO, Jordan JL, Van der Windt DA, Hill JC, Foster NE, Protheroe J. Effective treatment options for musculoskeletal pain in primary care: A systematic overview of current evidence. PLoS One. 2017;12(6):e0178621. doi:10.1371/journal.pone.0178621 PubMed

11.Santini A, Petruzzo A, Giannetta N, Ruggiero A, Di Muzio M, Latina R. Management of chronic musculoskeletal pain in veterans: a systematic review. Acta Biomed. Mar 31 2021;92(S2):e2021011. doi:10.23750/abm.v92iS2.11352 PubMed

12.Busse JW, Craigie S, Juurlink DN, et al. Guideline for opioid therapy and chronic noncancer pain. CMAJ. May 8 2017;189(18):E659-E666. doi:10.1503/cmaj.170363 PubMed

13.Hsu C, Vu K, Borg-Stein J. Prolotherapy: A Narrative Review of Mechanisms, Techniques, and Protocols, and Evidence for Common Musculoskeletal Conditions. Phys Med Rehabil Clin N Am. Feb 2023;34(1):165-180. doi:10.1016/j.pmr.2022.08.011 PubMed

14.Huang K, Cai H. Hypertonic dextrose prolotherapy in osteoarthritis: mechanisms, efficacy, and future research directions. Review. Front Endocrinol (Lausanne). 2025;16:1602727. doi:10.3389/fendo.2025.1602727 PubMed

15.Previtali D, Merli G, Di Laura Frattura G, Candrian C, Zaffagnini S, Filardo G. The Long-Lasting Effects of “Placebo Injections” in Knee Osteoarthritis: A Meta-Analysis. Cartilage. Dec 2021;13(1_suppl):185S-196S. doi:10.1177/1947603520906597 PubMed

16.Bélanger M, Allard J, de Arcos C, et al. Effect of Regenerative Injection Therapy on Function and Pain in Patients with Knee Osteoarthritis: A Randomized Crossover Study. Pain Med. 2012/08/01 2012;13(8):990-999. doi:10.1111/j.1526-4637.2012.01422.x

17.CADTH. Prolotherapy for Chronic Musculoskeletal Pain: A Review of Clinical Effectiveness and Guidelines. 2014. CADTH Rapid Response Report. Accessed March 16, 2026.

18.Institut national d’excellence en santé et en services sociaux (INESSS). Efficacité et innocuité de la prolothérapie dans le traitement de la douleur musculosquelettique chronique. 2024. Accessed April 28, 2026. https://www.inesss.qc.ca/en/publications/publications/publication/efficacite-et-innocuite-de-la-prolotherapie-dans-le-traitement-de-la-douleur-musculosquelettique-chronique.html

19.Martin C. Efficacy/Effectiveness of Prolotherapy in Treating Wrist Sprain/Strain or Repetitive Strain Injury (RSI): A Rapid Systematic Review. 2024. Accessed April 28, 2026. https://www.worksafebc.com/en/resources/health-care-providers/guides/efficacy-effectiveness-prolotherapy-treating-wrist-sprain-rsi

20.Martin C. Effectiveness of Prolotherapy in Shoulder Labral Tears: A Rapid Systematic Review. 2024. Accessed April 28, 2026. https://www.worksafebc.com/en/resources/health-care-providers/guides/effectiveness-prolotherapy-shoulder-labral-tears

21.Martin C. Effectiveness of Prolotherapy in Rotator Cuff Tendinopathy: A Rapid Systematic Review. 2024. Accessed April 28, 2026. https://www.worksafebc.com/en/resources/health-care-providers/guides/effectiveness-prolotherapy-rotator-cuff-tendinopathy

22.Ewart D, Sowerby C, Yang S, et al. Dextrose Prolotherapy for Musculoskeletal Pain: A Systematic Review. Department of Veterans Affairs (US). 2024.

23.Shea BJ, Reeves BC, Wells G, et al. AMSTAR 2: a critical appraisal tool for systematic reviews that include randomised or non-randomised studies of healthcare interventions, or both. BMJ. 2017;358:j4008. doi:10.1136/bmj.j4008 PubMed

24.Qafesha RM, Ishreiteh HA, Nassourah AL, Tawil OI, Mashaly D. Efficacy and Safety of Dextrose Prolotherapy Versus Corticosteroid Injections in Plantar Fasciitis: A Systematic Review and Meta-Analysis. J Foot Ankle Res. Mar 2026;19(1):e70135. doi:10.1002/jfa2.70135 PubMed

25.Saramantos A, Kyrgidis A, Venetis G, et al. Clinical Efficacy of Prolotherapy for Temporomandibular Joint Disorders: A Systematic Review and Meta-Analysis. Review. Clin Pract. Feb 27 2025;15(3):51. doi:10.3390/clinpract15030051 PubMed

26.Thamrongskulsiri N, Vitoonpong T, Itthipanichpong T, Limskul D, Tanpowpong T, Kuptniratsaikul S. Prolotherapy is not superior to control or placebo-based conservative treatments for rotator cuff tendinopathy: a systematic review and meta-analysis. Clin Shoulder Elb. Dec 2025;28(4):446-456. doi:10.5397/cise.2025.00570 PubMed

27.Zhou G, Hu Y, Wang S. Efficacy of dextrose prolotherapy for temporomandibular joint hypermobility: A systematic review and meta-analysis. Cranio. Nov 2025;43(6):1022-1031. doi:10.1080/08869634.2024.2419845 PubMed

28.Page MJ, Moher D, Bossuyt PM, et al. PRISMA 2020 explanation and elaboration: updated guidance and exemplars for reporting systematic reviews. BMJ. 2021;372:n160. doi:10.1136/bmj.n160 PubMed

29.O'Neill J, Tabish H, Welch V, et al. Applying an equity lens to interventions: using PROGRESS ensures consideration of socially stratifying factors to illuminate inequities in health. J Clin Epidemiol. 2014;67(1):56-64. doi:10.1016/j.jclinepi.2013.08.005 PubMed

30.Korownyk CS, Montgomery L, Young J, et al. PEER simplified chronic pain guideline: Management of chronic low back, osteoarthritic, and neuropathic pain in primary care. Can Fam Physician. Mar 2022;68(3):179-190. doi:10.46747/cfp.6803179 PubMed

31.Canada’s Drug Agency. Canada's Drug Agency Style: A Guide for Authors and Editors. 2025. Accessed January 1, 2026. https://www.cda-amc.ca/sites/default/files/pdf/style_guide_2025_digital.pdf

Appendix 1: Detailed Methods and Selection of Included Studies

Please note that this appendix has not been copy-edited.

What Is a Rapid Review?

Rapid reviews are based on accelerated and abbreviated SR methods, balancing timeliness with rigour, to allow for timely decision-making. Due to these abbreviated methods, rapid reviews have some limitations. For example, in our initial scoping of the topic, we identified an SR published by the US Veterans Affairs in 2024,22 which included literature from inception through February 2024. This SR22 was highly relevant, comprehensive, and methodologically robust, making it a well-aligned and appropriate baseline for the present rapid review. In consultation with the external requester, we set our search time frame from March 2024 onward and included and appraised this SR22 in the current rapid review. The included SRs published in this time frame also include older studies. Another example is that unlike in SRs, for which at least 2 independent reviewers are needed to screen studies to reduce selection bias, a single reviewer was required to include, extract the data, and appraise a study. Our rapid review intends to summarize the available evidence, rather than provide recommendations. These findings should not be interpreted as prescriptive guidance.

Literature Search Methods

An information specialist conducted a literature search on key resources including MEDLINE, Embase, the Cochrane Database of Systematic Reviews, the International HTA Database, the websites of health technology assessment (HTA) agencies in Canada and major international HTA agencies, as well as a focused internet search. The search approach was customized to retrieve a limited set of results, balancing comprehensiveness with relevance. The search strategy comprised both controlled vocabulary, such as the US National Library of Medicine’s MeSH (Medical Subject Headings), and keywords. Search concepts were developed based on the elements of the research questions and selection criteria. The main search concept was prolotherapy. Conference abstracts and clinical trial registry records were excluded. Retrieval was limited to the human population. The search was completed on March 23, 2026, and was limited to English-language documents published since January 1, 2024. The search strategy is available on request.

Selection Criteria and Methods

One reviewer screened citations and selected studies. In the first level of screening, titles and abstracts were reviewed and potentially relevant articles were retrieved and assessed for inclusion. The final selection of full-text articles was based on the inclusion criteria presented in Table 1.

Exclusion Criteria

Articles were excluded if they:

Critical Appraisal of Individual Studies

The included publications were critically appraised by 1 reviewer using the following tool as a guide: A MeaSurement Tool to Assess systematic Reviews 2 (AMSTAR 2)23 for SRs. Summary scores were not calculated for the included studies; rather, the strengths and limitations of each included publication were described narratively.

Data Extraction

One reviewer extracted data directly into standardized tables created in Microsoft Word, which were modified as necessary. The extracted information included study characteristics, methodology (e.g., study design), population, intervention, comparator, and results regarding the outcomes of interest.

One reviewer extracted information from the included studies using the PROGRESS-Plus29 tool to describe different population groups. Each included study was checked to determine if PROGRESS-Plus29 tool criteria were reported by study authors to describe the participants; detailed characteristics, if available, were then extracted and reported in Table 2 in Appendix 3. The main PROGRESS-Plus29 criteria include place of residence; race, ethnicity, culture, and/or language; occupation; gender and/or sex; religion; education; socioeconomic status; and social capital. As part of report writing, we discuss these characteristics across the evidence, where available, when presenting results within the text.

When reporting on sex, gender, race, or ethnicity in this Rapid Review, we planned to retain the language used by the original study authors, and, whenever possible, we referred to these groups based on guidance from Canada’s Drug Agency Style: A Guide for Authors and Editors31 at the time this rapid review was conducted, with an understanding that language is constantly evolving.

Appendix 2: Selection of Included Studies

Please note that this appendix has not been copy-edited.

Figure 1: Selection of Included Studies — PRISMA28 Flow Chart of Selected Reports

A flow diagram showing 279 citations were identified and 258 were excluded. There were 3 potentially relevant reports retrieved from other sources, for a total of 24 potentially relevant articles and grey literature reports retrieved for scrutiny. In total, 19 were excluded and 5 reports were included in the review.

SR = systematic review.

Appendix 3: Characteristics of Included Publications

Please note that this appendix has not been copy-edited.

Table 2: Characteristics of Included Systematic Reviews

Study citation, countries of eligible studies, funding source

Study designs and number of primary studies included

Population characteristics

Intervention and comparator(s)

Intervention characteristics

Clinical outcomes, length of follow-up

Qafesha et al. (2026)24

Countries of included studies eligible for the current review:

  • Egypt (n = 1)

  • India (n = 1)

  • Iran (n = 2)

  • Turkey (n = 3)

Funding source: None

Study design: SR and MA of RCTs and cohort studies

Articles with no language restriction published from inception to Octobera 2025

Number of included studies: 7 (5 RCTs, 2 comparative cohort studies); all relevant to the present review.

Adults (≥ 18 years) with plantar fasciitis

Number of participants: 567

Age (year), mean:

mean ages ranging from approximately 42 to 54 years

Sex or gender: predominance of female participants (up to 88% in 1 study); other sexes or genders were NR.

BMI: mean ranging from 27.7 kg/m2 to 32.5 kg/m2

Other PROGRESS-Plus criteria:b NR

Setting: NR

Intervention: Dextrose prolotherapy

Comparator:

  • Corticosteroid injections:

    • methylprednisolone acetate (40 mg/mL)

    • triamcinolone (used alone or in combination with local anesthetics)

Location of injections: NR

Number of injection sessions:

  • Single session (n = 3)

  • 2 sessions (n = 2)

  • 3 sessions: (n = 2)

Injection doses:

Dextrose concentrations ranged from 5% to 50% in their included studies and were diluted with local anesthetics

Use of imaging guidance:

  • Ultrasound guided (n = 4)

  • Palpation guided (n = 3)

Outcomes:

  • Pain-related functioning: Walking

  • Pain severity or intensity: VAS; NRS

  • Physical performance: foot function

  • Plantar fascia thickness

  • Adverse events or complications

Follow-up duration:

  • 12 weeks (n = 5)

  • 3 months (n = 1)

  • 36 months (n = 1)

Saramantos et al. (2025)25

Countries of included studies eligible for the current review: NR

Funding source: None

Study design: SR and MA of RCTs

Language restriction on articles: NR

Articles published from 1990 to September 2024

Number of included studies: 12 RCTs; 10 RCTs relevant to the present review.

Patients with TMD

Number of participants: 345

Age (year), mean: mean ages ranging from approximately 23 to 50 years

Sex or gender: The percentage of female participants from included primary studies ranged from 40% to 100%; other sexes or genders were NR.

Other PROGRESS-Plus criteria:b NR

Setting: NR

Intervention: Dextrose prolotherapy

Comparator:

  • placebo or other active comparators. Identified comparators:

    • placebo (saline [n = 6]; dry needling [n = 1])

    • ABI (n = 2)

    • dental occlusal splints (n = 1)

Location of injections: Intra-articular injections ± periarticular/masseter injections

Number of injection sessions:

  • Single session (n = 1)

  • 3 sessions: (n = 3)

  • 4 sessions: (n = 6)

Injection doses: Dextrose solutions ranged from 10% to 50% in their included studies

Use of imaging guidance: NR for relevant RCTs

Outcomes:

  • Pain-related functioning: Subluxation / jaw mobility

  • Pain severity or intensity: VAS; NRS

  • Physical performance: MIO; dislocation frequency; clicking

Follow-up duration: 1 month to 12 months (varied)

Thamrongskulsiri et al. (2025)26

Countries of included studies eligible for the current review: NR

Funding source: None

Study design: SR and MA of comparative studies

English-language articles published from inception to April 2025.

Number of included studies: 8 (all comparative observational studies); all relevant to the present review.

Adults with rotator cuff tendinopathy

Number of participants: 431

Age (year), mean: mean ages ranging from approximately 46 to 57 years

Other PROGRESS-Plus criteria:b NR

Setting: NR

Intervention: Dextrose prolotherapy + PT

Comparator:

  • placebo (normal saline [n = 5] + PT [n = 2])

  • active control (no injection + PT [n = 3])

Location of injections: NR

Number of injection sessions:

  • 3 sessions: (n = 1)

  • 6 to 8 sessions: (n = 2)

  • NR (n = 5)

Injection doses: Dextrose solutions ranged from 12.5% to 25% in their included studies

Use of imaging guidance:

  • Ultrasound guided (n = 6)

  • Landmark-based injection (n = 2)

Outcomes:

  • Pain-related functioning: SPADI

  • Pain severity or intensity: VAS

  • Physical performance: ROM

Follow-up duration: 3 months to 12 months (varied)

Zhou et al. (2025)27

Countries of included studies eligible for the current review:

  • Egypt (n = 3)

  • India (n = 2)

  • Turkey (n = 2)

Funding source: None

Study design: SR and MA of RCTs

English-language articles published from inception to August 2024.

Number of included studies: 8 (all RCTs); 7 relevant to the present review.

Adult patients with TMJ hypermobility

Number of participants: 236

Age (year), mean: mean ages ranging from approximately 23 to 32 years

Sex or gender: The number of male participants from included primary studies ranged from 0 to 18; other sexes or genders were NR.

Other PROGRESS-Plus criteria:a,b NR

Setting: NR

Intervention: Dextrose prolotherapy

Comparator:

  • placebo or any other active intervention. Identified comparators:

    • placebo (saline) (n = 3)

    • ABI (n = 3)

    • botulinum toxin (n = 1)

Location of injections: Intra-articular TMJ injections ± periarticular structures

Number of injection sessions:

  • Single session (n = 2)

  • 3 sessions: (n = 2)

  • 4 sessions: (n = 3)

Injection doses: Dextrose solutions ranged from 10% to 50% in their included studies

Use of imaging guidance: NR

Outcomes:

  • Pain severity or intensity: VAS

  • Physical performance: MMO; dislocation frequency

Follow-up duration: 1 month to 12 months (varied)

Ewart et al. (2024)22

Countries/regions of included studies eligible for the current review:

  • Asia (n = 20)

  • Australia/New Zealand (n = 4)

  • Europe (n = 24)

  • Middle East (n = 26)

  • North America (n = 11)

  • Others (n = 1)

Funding source: Department of Veterans Affairs, Veterans Health Administration, Health Systems Research

Study design: SR and MA (for certain pain conditions) of RCTs and observational studies

English-language articles published from inception to February 2024.

Number of included studies: 91 articles, reporting 90 unique studies (80 RCTs, 10 observational studies); 86 relevant to the present review.

Adults (≥ 18 years) with acute or chronic musculoskeletal pain:

  • Knee osteoarthritis and other knee pain

  • Shoulder and elbow pain

  • Plantar fasciitis and other foot pain

  • Chronic low back pain

  • TMJ dysfunction and pain

  • Other pain condition

Number of participants:

  • < 50 (n = 40)

  • 50 to 99 (n = 31)

  • 100 to 199 (n = 15)

  • 200 to 300 (n = 1)

Age (year), mean/median:

  • < 30 (n = 5)

  • 30 to 64 (n = 68)

  • ≥ 65 (n = 1)

  • NR (n = 12)

Sex or gender: The percentage of women reported from included primary studies:

  • < 30% (n = 2)

  • 30% to 59% (n = 29)

  • ≥ 65% (n = 43)

  • NR (n = 12)

Other sexes or genders were NR.

BMI: reported separately for each study

Other PROGRESS-Plus criteria:b NR

Setting: Outpatient

Intervention: Dextrose prolotherapy (hypertonic, > 5%)

Comparator: Any

Identified comparators related to the present review:

  • Normal saline or water ± local anesthetic (n = 25)

  • Corticosteroids injection (n = 14)

  • HA (n = 4)

  • ABIc (n = 10)

  • Other injectablesd (n = 8)

  • PT or exercise program (n = 9)

  • Other non-injectable comparatore (n = 11)

Location of injections: Intra-articular and/or periarticular, depending on condition

Number of injection sessions:

  • Single sessions (n = 24)

  • 2 to 3 sessions (n = 50)

  • 3 to 6 sessions (n = 12)

Injection doses: Dextrose solutions ranged from 5% to 50% in their included studies

Use of imaging guidance:

  • Ultrasound guidance (n = 30)

  • Fluoroscopy (n = 3)

  • None (n = 53)

Outcomes:

  • Pain-related functioning or interference

  • Pain severity or intensity

  • Physical performance (e.g., ROM, timed up and go)

  • Health-related quality of life

  • Adverse events

Follow-up duration:

  • < 1 month (n = 2)

  • 1 to 5 months (n = 42)

  • 6 to 11 months (n = 22)

  • ≥ 12 months (n = 20)

ABI = autologous blood injection; HA = hyaluronic acid; MA = meta-analysis; MIO = maximal incisor opening; MMO = maximal mouth opening; NR = not reported; NRS = numerical rating scale; PT = physical therapy; RCT = randomized controlled trial; ROM = range of motion; SPADI = shoulder pain and disability index; SR = systematic review; TMD = temporomandibular disorders; TMJ = Temporomandibular joint; VAS = visual analogue scale.

In this table, n refers to number of studies reported on a certain characteristic item in each SR.

aThe abstract of the article stated the date as August 2025, but the methods in the main text stated the date as October 2025.

bThe main PROGRESS-Plus criteria include place of residence, race, ethnicity, culture, language, occupation, gender, sex, religion, education, socioeconomic status, and social capital, personal characteristics associated with discrimination (e.g., age, disability), features of relationships, and time-dependent relationships.29

cIncludes platelet-rich plasma, autologous blood, and autologous conditioned serum.

dIncludes botulinum toxin, erythropoietin, and ozone.

eIncludes radiofrequency pulses, extracorporeal shock wave therapy, laser, occlusal splint, arthrocentesis, paraffin wax, and NSAIDs.

Appendix 4: Critical Appraisal of Included Publications

Please note that this appendix has not been copy-edited.

Table 3: Strengths and Limitations of the Qafesha et al. (2026) Study24 Using AMSTAR 223

AMSTAR 2 item

Domain type

Judgment

Support for judgment

1. Did the research questions and inclusion criteria for the review include the components of PICO?

Noncritical

Yes

The review clearly defines population (adults with plantar fasciitis), interventions (dextrose prolotherapy), comparator (corticosteroid injections), and outcomes (VAS, FFI, adverse events).

2. Did the report of the review contain an explicit statement that the review methods were established prior to the conduct of the review and did the report justify any significant deviations from the protocol?

Critical

Yes

The review reports PROSPERO registration (CRD420251126876), indicating predefined methods. No deviations were discussed.

3. Did the review authors explain their selection of the study designs for inclusion in the review?

Noncritical

Yes

Authors explicitly justify inclusion of both RCTs and cohort studies due to limited RCT evidence for some outcomes.

4. Did the review authors use a comprehensive literature search strategy?

Critical

Yes

Multiple databases (PubMed, Cochrane, Web of Science, Scopus, Google Scholar) searched from inception with no language restrictions; search strategy based on PICOS. However, they did not conduct a grey literature search.

5. Did the review authors perform study selection in duplicate?

Noncritical

Yes

Two reviewers independently screened titles/abstracts and full texts, with a third reviewer resolving disagreements.

6. Did the review authors perform data extraction in duplicate?

Noncritical

Yes

Data extraction was conducted independently by 2 reviewers using a predefined form.

7. Did the review authors provide a list of excluded studies and justify the exclusions?

Critical

Yes

The list of excluded studies with reasons are provided in supplementary material.

8. Did the review authors describe the included studies in adequate detail?

Noncritical

Yes

Detailed tables describe study design, population, interventions, dosing, follow-up, and outcomes.

9. Did the review authors use a satisfactory technique for assessing the RoB in individual studies that were included in the review?

Critical

Yes

Two independent reviewers evaluated the risk of bias via the Cochrane RoB 2 tool for RCTs, and Newcastle–Ottawa Scale for cohort studies, with domain-level reporting.

10. Did the review authors report on the sources of funding for the studies included in the review?

Noncritical

Yes

Funding status is reported in study characteristics table.

11. If meta-analysis was performed did the review authors use appropriate methods for statistical combination of results?

Critical

Yes

Use of mean differences, heterogeneity assessment (χ2, I2), fixed- or random-effects models, subgroup and sensitivity analyses.

12. If meta-analysis was performed, did the review authors assess the potential impact of RoB in individual studies on the results of the meta-analysis or other evidence synthesis?

Noncritical

Yes

Sensitivity analyses (via leave-1-out [jackknife] method) and RoB assessments were presented. The influence of individual studies on pooled results were estimated and discussed.

13. Did the review authors account for RoB in individual studies when interpreting/discussing the results of the review?

Critical

Yes

Authors explicitly discussed bias (e.g., lack of blinding, missing data) and its implications for confidence in findings.

14. Did the review authors provide a satisfactory explanation for, and discussion of, any heterogeneity observed in the results of the review?

Noncritical

Yes

Heterogeneity was explored via subgroup analysis (e.g., ultrasound vs. palpation guidance), and sensitivity analyses were conducted.

15. If they performed quantitative synthesis did the review authors carry out an adequate investigation of publication bias (small study bias) and discuss its likely impact on the results of the review?

Critical

Yes

Egger’s test was used; authors acknowledged limitations due to small number of studies and interpreted them cautiously.

16. Did the review authors report any potential sources of conflict of interest, including any funding they received for conducting the review?

Noncritical

Yes

Explicit statements of conflicts of interest and funding are clearly provided.

AMSTAR 2 = A MeaSurement Tool to Assess systematic Reviews 2; FFI = foot function index; PICOS = population, intervention, comparison, outcomes, study design; RCT = randomized controlled trial; RoB = risk of bias; VAS = visual analogue scale; vs. = versus.

Table 4: Strengths and Limitations of the Saramantos et al. (2025) Study25 Using AMSTAR 223

AMSTAR 2 item

Domain type

Judgment

Support for judgment

1. Did the research questions and inclusion criteria for the review include the components of PICO?

Noncritical

Yes

Population, intervention, comparator, and outcomes are clearly described, according to the PICO framework, presented in Supplementary Table S2.

2. Did the report of the review contain an explicit statement that the review methods were established prior to the conduct of the review and did the report justify any significant deviations from the protocol?

Critical

No

The paper explicitly states that review protocol preregistration was not performed.

3. Did the review authors explain their selection of the study designs for inclusion in the review?

Noncritical

Yes

The review explicitly focused on RCTs and explains that RCTs are the superior form of evidence for clinical conclusions.

4. Did the review authors use a comprehensive literature search strategy?

Critical

Partial Yes

They searched MEDLINE, Scopus, and CENTRAL, screened conferences, and grey literature, checked references, and provided a search example and supplementary strategies. However, no clear justification for any publication restrictions was given.

5. Did the review authors perform study selection in duplicate?

Noncritical

Yes

Two independent investigators conducted the search and resolved disagreements through a third investigator.

6. Did the review authors perform data extraction in duplicate?

Noncritical

Yes

Two authors independently extracted data using a standardized form.

7. Did the review authors provide a list of excluded studies and justify the exclusions?

Critical

No

The review provides counts and categories of excluded studies but not a citation-level list of excluded full-text studies with reasons.

8. Did the review authors describe the included studies in adequate detail?

Noncritical

Yes

Included studies were described in descriptive tables and text, covering interventions, comparators, follow-up, and outcomes.

9. Did the review authors use a satisfactory technique for assessing the RoB in individual studies that were included in the review?

Critical

Yes

The review used the RevMan risk of bias tool and presented risk of bias figures.

10. Did the review authors report on the sources of funding for the studies included in the review?

Noncritical

No

Funding sources for the included primary studies were not reported.

11. If meta-analysis was performed did the review authors use appropriate methods for statistical combination of results?

Critical

Yes

They pooled weighted mean differences, assessed heterogeneity with I2, used random-effects models for higher heterogeneity, and conducted subgroup and sensitivity analyses.

12. If meta-analysis was performed, did the review authors assess the potential impact of RoB in individual studies on the results of the meta-analysis or other evidence synthesis?

Noncritical

No

RoB was presented, but no clear analysis linked study bias to the pooled results.

13. Did the review authors account for RoB in individual studies when interpreting/discussing the results of the review?

Critical

Partial Yes

The authors acknowledge limited and imperfect evidence, but the interpretation does not clearly integrate specific RoB findings into each conclusion.

14. Did the review authors provide a satisfactory explanation for, and discussion of, any heterogeneity observed in the results of the review?

Noncritical

Yes

They conducted subgroup and sensitivity analyses to investigate heterogeneity and used random-effects models when needed.

15. If they performed quantitative synthesis did the review authors carry out an adequate investigation of publication bias (small study bias) and discuss its likely impact on the results of the review?

Critical

Partial Yes

Funnel plots were examined and reported in the supplementary file, but the discussion of their likely impact appears limited.

16. Did the review authors report any potential sources of conflict of interest, including any funding they received for conducting the review?

Noncritical

Yes

The review reports no external funding and no conflicts of interest.

AMSTAR 2 = A MeaSurement Tool to Assess systematic Reviews 2; PICOS = population, intervention, comparison, outcomes, study design; RCT = randomized controlled trial; RoB = risk of bias.

Table 5: Strengths and Limitations of the Thamrongskulsiri et al. (2025) Study26 Using AMSTAR 223

AMSTAR 2 item

Domain type

Judgment

Support for judgment

1. Did the research questions and inclusion criteria for the review include the components of PICO?

Noncritical

Partial Yes

The information about the population, intervention, comparator, and outcomes can be found in the review, but they are not clearly defined in the methods.

2. Did the report of the review contain an explicit statement that the review methods were established prior to the conduct of the review and did the report justify any significant deviations from the protocol?

Critical

Yes

The review was registered in PROSPERO (CRD42024615400). No deviations were reported.

3. Did the review authors explain their selection of the study designs for inclusion in the review?

Noncritical

Partial Yes

Authors limited inclusion to comparative clinical studies with evidence levels 1 to 3, but the rationale for this design restriction was not fully explained.

4. Did the review authors use a comprehensive literature search strategy?

Critical

Partial Yes

The review searched PubMed, Ovid, and Scopus from inception and used duplicate independent searching. However, they did not conduct a grey literature search.

5. Did the review authors perform study selection in duplicate?

Noncritical

Yes

Two researchers independently reviewed titles, abstracts, and full texts, with third-author resolution of discrepancies.

6. Did the review authors perform data extraction in duplicate?

Noncritical

Partial Yes

The paper clearly states duplicate eligibility review, but it does not explicitly state that full data extraction itself was independently duplicated in the same way.

7. Did the review authors provide a list of excluded studies and justify the exclusions?

Critical

No

Authors reported the number of excluded abstracts and full texts, but not a study-level excluded list with justifications.

8. Did the review authors describe the included studies in adequate detail?

Noncritical

Yes

Tables reported age, follow-up, sample size, outcomes, and study/intervention details.

9. Did the review authors use a satisfactory technique for assessing the RoB in individual studies that were included in the review?

Critical

No

The quality of the included studies was assessed using 2 tools: MINORS and MCMS, but these are not dedicated domain-based tools for assessing RoB in studies.

10. Did the review authors report on the sources of funding for the studies included in the review?

Noncritical

No

Funding sources for the included primary studies are not reported.

11. If meta-analysis was performed did the review authors use appropriate methods for statistical combination of results?

Critical

Yes

Authors used RevMan, pooled MDs and ORs with 95% CIs, assessed heterogeneity with chi-square and I2, and selected fixed- or random-effects models based on heterogeneity.

12. If meta-analysis was performed, did the review authors assess the potential impact of RoB in individual studies on the results of the meta-analysis or other evidence synthesis?

Noncritical

No

Study quality was scored, but there was no clear analysis of how bias or methodological limitations affected pooled estimates.

13. Did the review authors account for RoB in individual studies when interpreting/discussing the results of the review?

Critical

Partial Yes

The discussion acknowledges methodological limitations, language bias, and heterogeneity, but it does not clearly integrate study-level bias assessments into interpretation.

14. Did the review authors provide a satisfactory explanation for, and discussion of, any heterogeneity observed in the results of the review?

Noncritical

Yes

The authors discuss substantial heterogeneity in injection protocols, follow-up duration, and outcome measures, and explain that subgroup meta-analysis was limited by this heterogeneity.

15. If they performed quantitative synthesis did the review authors carry out an adequate investigation of publication bias (small study bias) and discuss its likely impact on the results of the review?

Critical

No

They acknowledge possible publication bias and language bias, but no formal investigation of publication bias was reported.

16. Did the review authors report any potential sources of conflict of interest, including any funding they received for conducting the review?

Noncritical

Yes

The review reports no conflict of interest and no funding.

AMSTAR 2 = A MeaSurement Tool to Assess systematic Reviews 2; CI = confidence interval; MDs = mean differences; OR = odds ratio; MCMS = Modified Coleman Methodology Score; MINORS = Methodological Index for Non-Randomized Studies; RCT = randomized controlled trial; RoB = risk of bias.

Table 6: Strengths and Limitations of the Zhou et al. (2025) Study27 Using AMSTAR 223

AMSTAR 2 item

Domain type

Judgment

Support for judgment

1. Did the research questions and inclusion criteria for the review include the components of PICO?

Noncritical

Yes

The review explicitly states population, intervention, comparator, outcomes, and study type using a PICOS-based framework.

2. Did the report of the review contain an explicit statement that the review methods were established prior to the conduct of the review and did the report justify any significant deviations from the protocol?

Critical

Yes

The protocol was registered in PROSPERO before the study began (CRD42024574666). No deviations were reported.

3. Did the review authors explain their selection of the study designs for inclusion in the review?

Noncritical

Partial Yes

The review restricted inclusion to RCTs but provided little explicit methodological justification for selecting only that design.

4. Did the review authors use a comprehensive literature search strategy?

Critical

Partial Yes

They searched PubMed, CENTRAL, Embase, Scopus, and Web of Science, also searched Google Scholar grey literature, checked reference lists, used MeSH/free-text terms, and involved an experienced medical librarian. However, they did not conduct a grey literature search.

5. Did the review authors perform study selection in duplicate?

Noncritical

Yes

Two independent reviewers screened studies, with disagreements resolved by a third reviewer.

6. Did the review authors perform data extraction in duplicate?

Noncritical

Yes

Two reviewers independently extracted and re-reviewed the data, with third reviewer cross-checking.

7. Did the review authors provide a list of excluded studies and justify the exclusions?

Critical

No

The paper reports numbers and broad reasons for exclusion, but not a study-level list of excluded full texts with individual justifications.

8. Did the review authors describe the included studies in adequate detail?

Noncritical

Yes

The review summarizes country, year, sample size, intervention protocols, follow-up, and outcomes, and provides detailed study characteristics.

9. Did the review authors use a satisfactory technique for assessing the RoB in individual studies that were included in the review?

Critical

Yes

The Cochrane Collaboration RoB 2 tool was used for the included RCTs, which is an appropriate tool.

10. Did the review authors report on the sources of funding for the studies included in the review?

Noncritical

No

No reporting of funding sources for the included primary studies was provided.

11. If meta-analysis was performed did the review authors use appropriate methods for statistical combination of results?

Critical

Yes

They used RevMan, pooled mean differences with 95% CIs, assessed heterogeneity with Q and I2, and used descriptive synthesis when pooling was not feasible.

12. If meta-analysis was performed, did the review authors assess the potential impact of RoB in individual studies on the results of the meta-analysis or other evidence synthesis?

Noncritical

No

RoB was assessed, but no clear analysis of how study RoB affected pooled estimates was reported.

13. Did the review authors account for RoB in individual studies when interpreting/discussing the results of the review?

Critical

Yes

The discussion and conclusions repeatedly describe the evidence as low quality and urge caution in interpretation.

14. Did the review authors provide a satisfactory explanation for, and discussion of, any heterogeneity observed in the results of the review?

Noncritical

Partial Yes

Heterogeneity was quantified and acknowledged, but the exploration of its sources was limited.

15. If they performed quantitative synthesis did the review authors carry out an adequate investigation of publication bias (small study bias) and discuss its likely impact on the results of the review?

Critical

No

They explicitly state that funnel plots were not drawn because of the small number of studies, and no alternative assessment or impact discussion was provided.

16. Did the review authors report any potential sources of conflict of interest, including any funding they received for conducting the review?

Noncritical

Yes

The review reports no conflict of interest and no funding.

AMSTAR 2 = A MeaSurement Tool to Assess systematic Reviews 2; PICOS = population, intervention, comparison, outcomes, and study design; RCT = randomized controlled trial; RoB = risk of bias; VAS = visual analogue scale.

Table 7: Strengths and Limitations of the Ewart et al. (2024) Study22 Using AMSTAR 223

AMSTAR 2 item

Domain type

Judgment

Support for judgment

1. Did the research questions and inclusion criteria for the review include the components of PICO?

Noncritical

Yes

The review clearly defines population, intervention, comparators, outcomes, and study designs under eligibility criteria and key questions.

2. Did the report of the review contain an explicit statement that the review methods were established prior to the conduct of the review and did the report justify any significant deviations from the protocol?

Critical

Yes

The authors report that the review protocol was registered in PROSPERO (CRD42024531179) before conducting the review.

3. Did the review authors explain their selection of the study designs for inclusion in the review?

Noncritical

Yes

Inclusion of RCTs and observational studies (with justification tied to outcomes like adverse events) is explicitly described in eligibility criteria.

4. Did the review authors use a comprehensive literature search strategy?

Critical

Yes

Multiple databases were searched and detailed search strategies are provided in the appendix.

5. Did the review authors perform study selection in duplicate?

Noncritical

Yes

Study screening and selection were conducted by 2 reviewers.

6. Did the review authors perform data extraction in duplicate?

Noncritical

Yes

Data extraction procedures indicate verification or independent extraction by 2 reviewers.

7. Did the review authors provide a list of excluded studies and justify the exclusions?

Critical

Yes

The appendix includes a list of excluded studies along with reasons for exclusion.

8. Did the review authors describe the included studies in adequate detail?

Noncritical

Yes

Characteristics of included studies are reported in detailed tables describing populations, interventions, comparators, and outcomes.

9. Did the review authors use a satisfactory technique for assessing the RoB in individual studies that were included in the review?

Critical

Yes

RoB assessments are reported for included studies using established appraisal methods: Cochrane RoB-2 for RCTs, ROBINS-I for comparative cohort studies, and Joanna Briggs Institute Critical Appraisal Tool for Cohort Studies for 1 pre–post observational study.

10. Did the review authors report on the sources of funding for the studies included in the review?

Noncritical

Yes

Funding information for included studies is reported, if available in the primary studies.

11. If meta-analysis was performed did the review authors use appropriate methods for statistical combination of results?

Critical

Yes

Meta-analysis conducted when appropriate (≥ 3 studies), with structured grouping, and narrative synthesis otherwise.

12. If meta-analysis was performed, did the review authors assess the potential impact of RoB in individual studies on the results of the meta-analysis or other evidence synthesis?

Noncritical

Yes

RoB findings were considered when interpreting results and evidence certainty.

13. Did the review authors account for RoB in individual studies when interpreting/discussing the results of the review?

Critical

Yes

The authors note that many included studies had high RoB and incorporate this into the interpretation of findings.

14. Did the review authors provide a satisfactory explanation for, and discussion of, any heterogeneity observed in the results of the review?

Noncritical

Yes

Variability in intervention protocols, patient populations, and outcomes is discussed as a source of heterogeneity.

15. If they performed quantitative synthesis did the review authors carry out an adequate investigation of publication bias (small study bias) and discuss its likely impact on the results of the review?

Critical

Partial Yes

Publication bias considered within GRADE domain (“other considerations”), but no clear formal methods (e.g., funnel plots) consistently reported.

16. Did the review authors report any potential sources of conflict of interest, including any funding they received for conducting the review?

Noncritical

Yes

Funding sources and institutional affiliations of the review authors are reported.

AMSTAR 2 = A MeaSurement Tool to Assess systematic Reviews 2; GRADE = Grading of Recommendations Assessment, Development and Evaluation; RCT = randomized controlled trial; RoB = risk of bias; ROBINS-I = Risk of Bias In Non-Randomized Studies of Interventions.

Appendix 5: Main Study Findings

Please note that this appendix has not been copy-edited.

Table 8: Summary of Findings by Outcome and Comparator — Knee Osteoarthritis; Dextrose Prolotherapy vs. Placebo

Citation

Evidence source, number of participants (intervention vs. comparator)

Comparator, outcome measure

Baseline, mean (SD)

Follow-up, mean (SD)

Relative effect, mean difference (95% CI)

P value (between groups)

Intervention

Comparator

Intervention

Comparator

Pain-related functioning

Ewart et al. (2024)22

1 RCT; Hsieh et al. (2022)

52 vs. 52 participants

Normal saline

WOMAC physical function (1 week, 1, 3, 6 months)a

523.5 (318.1)

513.5 (326.8)

1 week: 512.8 (303.9)

1 month: 491.9 (287.2)

3 months: 415.6 (299.6)

6 months: 529.8 (292.7)

1 week: 500.8 (330.0)

1 month: 495.8 (295.5)

3 months: 434.3 (301.2)

6 months: 540.9 (298.2)

1 week: 12.0 (NR)

1 month: −3.9 (NR)

3 months: −18.7 (NR)

6 months: −11.1 (NR)

NR

Ewart et al. (2024)22

1 RCT; Sert et al. (2020)

22 vs. 22 participants

Normal saline

WOMAC Total (6, 18 weeks)a

68.7 (11.4)

69.2 (17.6)

6 weeks: 44.4 (11.5)

18 weeks: 32.7 (11.6)

6 weeks: 50.5 (16.7)

18 weeks: 46.7 (13.5)

6 weeks: −6.1 (NR)

18 weeks: −14.0 (NR)

6 weeks: 0.118

18 weeks: 0.002

Ewart et al. (2024)22

1 RCT; Sit et al. (2020)

38 vs. 38 participants

Normal saline

WOMAC Total (16, 26, 52 weeks)a

49.1 (21.8)

45.6 (21.2)

16 weeks: 30.4 (NR)

26 weeks: 28.8 (NR)

52 weeks: 28.3 (NR)

16 weeks: 32.4 (NR)

26 weeks: 33.3 (NR)

52 weeks: 36.0 (NR)

16 weeks: −4.33 (−12.27 to 3.62)

26 weeks: −7.34 (−15.28 to 0.61)

52 weeks: −9.65 (−17.77 to −1.53)

16 weeks: 0.285

26 weeks: 0.285

52 weeks: 0.020

Ewart et al. (2024)22

1 RCT; Rabago et al. (2013a)

33 vs. 31 participants

Normal saline

Modified WOMAC Total (5, 9, 12, 24, 52 weeks)

63.1 (15.0)

62.7 (14.3)

5 weeks: 71.2 (NR)

9 weeks: 77.1 (NR)

12 weeks: 76.5 (NR)

24 weeks: 79.1 (NR)

52 weeks: 78.6 (NR)

5 weeks: 68.2 (NR)

9 weeks: 70.0 (NR)

12 weeks: 70.9 (NR)

24 weeks: 71.0 (NR)

52 weeks: 70.5 (NR)

5 weeks: 3.0 (NR)

9 weeks: 7.1 (NR)

12 weeks: 5.6 (NR)

24 weeks: 8.1 (NR)

52 weeks: 8.0 (NR)

NR

Physical performance

Ewart et al. (2024)22

1 RCT; Hsieh et al. (2022)

52 vs. 52 participants

Normal saline

Regular Walking Speed, m/s, Chair Stand Test (1 week, 1, 3, 6 months)

Regular Walking Speed:

0.89 (0.32)

0.92 (0.37)

1 week: 0.94 (0.27)

1 month: 0.98 (0.37)

3 months: 0.99 (0.46)

6 months: 0.95 (0.42)

1 week: 0.95 (0.38)

1 month: 1.0 (0.40)

3 months: 0.98 (0.39)

6 months: 0.94 (0.38)

1 week: 0.0 (NR)

1 month: 0.0 (NR)

3 months: 0.0 (NR)

6 months: 0.0 (NR)

1 week: 0.005

1 month: 0.340

3 months: 0.001

6 months: < 0.001

Ewart et al. (2024)22

1 RCT; Hsieh et al. (2022)

52 vs. 52 participants

Normal saline

Regular Walking Speed, m/s, Chair Stand Test (1 week, 1, 3, 6 months)

Chair Stand Test:

20.5 (12.6)

21.4 (12.4)

1 week: 19.0 (10.5)

1 month: 18.0 (11.1)

3 months: 18.1 (10.6)

6 months: 19.2 (12.5)

1 week: 21.0 (11.5)

1 month: 19.4 (10.3)

3 months: 18.7 (11.3)

6 months: 19.5 (11.0)

1 week: −2.0 (NR)

1 month: −1.4 (NR)

3 months: −0.6 (NR)

6 months: −0.3 (NR)

1 week: < 0.001

1 month: NR

3 months: NR

6 months: NR

Ewart et al. (2024)22

1 RCT; Reeves et al. (2000)

Total participants randomized: 77 (68 analyzed) but n per arm NR

Saline (with 0.075% lidocaine 9 mL)

Flexion range (6 months)

112.4 (19.5)

117.8 (11.3)

125.6 (8.6)

125.4 (7.5)

0.2 (NR)

NR

Ewart et al. (2024)22

1 RCT; Sit et al. (2020)

38 vs. 38 participants

Normal saline

TUG (16, 26, 52 weeks)a

12.6 (7.1)

12.5 (4.3)

16 weeks: 10.9 (NR)

26 weeks: 10.1 (NR)

52 weeks: 9.9 (NR)

16 weeks: 11.9 (NR)

26 weeks: 11.7 (NR)

52 weeks: 10.2 (NR)

16 weeks: −1.13 (−2.74 to 0.49)

26 weeks: −1.73, (−3.34 to −0.12)

52 weeks: −0.3 (−2.38 to 0.92)

16 weeks: 0.170

26 weeks: < 0.05

52 weeks: 0.385

Pain intensity or severity

Ewart et al. (2024)22

1 RCT; Hsieh et al. (2022)

52 vs. 52 participants

Normal saline

WOMAC Pain (1 week, 1, 3, 6 months)

230.8 (97.9)

216.9 (89.4)

1 week: 214.7 (85.1)

1 month: 194.7 (94.4)

3 months: 186.6 (92.1)

6 months: 180.3 (77.9)

1 week: 205.8 (95.9)

1 month: 192.4 (76.9)

3 months: 200.6 (93.4)

6 months: 199.6 (91.9)

1 week: 8.9 (NR)

1 month: 2.3 (NR)

3 months: −14.0 (NR)

6 months: −19.3 (NR)

NR

Ewart et al. (2024)22

1 RCT; Sit et al. (2020)

38 vs. 38 participants

Normal saline

VAS (16, 26, 52 weeks)

63.1 (21.2)

60.1 (19.2)

16 weeks: 41.63 (NR)

26 weeks: 33.65 (NR)

52 weeks: 35.78 (NR)

16 weeks: 44.48 (NR)

26 weeks: 38.92 (NR)

52 weeks: 46.05 (NR)

16 weeks: −3.70 (−13.83 to 6.43)

26 weeks: −6.73 (−16.86 to 3.40)

52 weeks: −10.98 (−21.36 to 0.61)

16 weeks: 0.473

26 weeks: 0.192

52 weeks: 0.038

Ewart et al. (2024)22

1 RCT; Sert et al. (2020)

22 vs. 22 participants

Normal saline

VAS pain activity (6, 18 weeks)

7.2 (1.0)

7.4 (2.0)

6 weeks: 4.1 (1.8)

18 weeks: 1.1 (1.9)

6 weeks: 4.9 (2.2)

18 weeks: 4.6 (1.8)

6 weeks: −0.8 (NR)

18 weeks: −3.5 (NR)

6 weeks: NR

18 weeks: < 0.001

Ewart et al. (2024)22

1 RCT; Rabago et al. (2013a)

33 vs. 31 participants

Waitlist

PRTEE pain domain (4, 8, 16, 32 weeks)

24.2 (2.7)

24.8 (2.6)

4 weeks: 16.2 (2.6)

8 weeks: 15.5 (3.0)

16 weeks: 13.6 (3.6)

32 weeks: 11.1 (3.3)

4 weeks: 22.4 (2.5)

8 weeks: 23.2 (2.9)

16 weeks: 20.9 (3.5)

32 weeks: NR (3.3)

4 weeks: −6.2 (NR)

8 weeks: −7.7 (NR)

16 weeks: −7.3 (NR)

32 weeks: NR

4 weeks: ≥ 0.05

8 weeks: ≥ 0.05

16 weeks: ≥ 0.05

32 weeks: NR

Ewart et al. (2024)22

1 RCT; Reeves et al. (2000)

Total participants randomized: 77 (68 analyzed) but n per arm NR

Saline (with 0.075% lidocaine 9 mL)

VAS pain with walking (6 months)a

3.9 (2.8)

3.8 (2.2)

2.6 (2.0)

2.9 (2.2)

−0.3 (NR)

NR

Health-related quality of life

Ewart et al. (2024)22

1 RCT; Sit et al. (2020)

38 vs. 38 participants

Normal saline

EuroQol-5D Index (26, 52 weeks)

0.569 (0.295)

0.558 (0.318)

26 weeks: 0.73 (NR)

52 weeks: 0.72 (NR)

26 weeks: 0.62 (NR)

52 weeks: 0.63 (NR)

26 weeks: 0.10 (−0.004 to 0.21)

52 weeks: 0.08 (−0.02 to 0.19)

26 weeks: 0.058

52 weeks: 0.126

Ewart et al. (2024)22

1 RCT; Sert et al. (2020)

22 vs. 22 participants

Normal saline

SF-36 Physical score, SF-36 Mental score (6, 18 weeks)

Physical score: 34.1 (8.9)

30.0 (7.4)

6 weeks: 41.2 (8.9)

18 weeks: 48.5 (7.5)

6 weeks: 37.0 (10.1)

18 weeks: 39.6 (8.5)

6 weeks: 4.2 (NR)

18 weeks: 8.9 (NR)

6 weeks: NR

18 weeks: 0.124

Ewart et al. (2024)22

1 RCT; Sert et al. (2020)

22 vs. 22 participants

Normal saline

SF-36 Physical score, SF-36 Mental score (6, 18 weeks)

Mental score: 45.4 (10.9)

46.6 (13.0)

6 weeks: 52.7 (9.1)

18 weeks: 53.5 (6.8)

6 weeks: 48.7 (11.9)

18 weeks: 52.0 (7.7)

6 weeks: 4.0 (NR)

18 weeks: 1.5 (NR)

6 weeks: NR

18 weeks: NR

CI = confidence interval; EuroQoL-5D = European Quality of Life-5 dimensions; NR = not reported; PRTEE = Patient-rated Tennis Elbow Evaluation; RCT = randomized controlled trial; SD = standard deviation; SF-36 = Short Form (36) Health Survey; SMD = standardized mean difference; SR = systematic review; TUG = timed up and go; VAS = visual analogue scale; vs. = versus; WOMAC = Western Ontario and McMaster Universities Osteoarthritis Index.

aAdditional results related to this outcome measure are available in the original SR.22

Table 9: Summary of Findings by Outcome and Comparator — Knee Osteoarthritis; Dextrose Prolotherapy vs. Other Comparators

Citation

Evidence source, number of participants (intervention vs. comparator)

Comparator, outcome measure

Baseline, mean (SD)

Follow-up, mean (SD)

Relative effect, mean difference (95% CI)

P value (between groups)

Intervention

Comparator

Intervention

Comparator

Pain-related functioning

Ewart et al. (2024)22

SR with MA (3 RCTs)

91 vs. 91 participants

PRP

WOMAC score (6 months)

NR

NR

NR

NR

SMD = 2.24

(−3.85 to 8.33)

NR

Ewart et al. (2024)22

SR with MA (3 RCTs)

81 vs. 79 participants

PT or home exercise program

WOMAC score at short-term follow‑up (1 to 1.5 month)

NR

NR

NR

NR

SMD = −0.81

(−8.93 to 7.30)

NR

Ewart et al. (2024)22

SR with MA (3 RCTs)

81 vs. 79 participants

PT or home exercise program

WOMAC score at medium-term follow-up (3 to 4 months)

NR

NR

NR

NR

SMD = −1.13

(−15.68 to 13.41)

NR

Ewart et al. (2024)22

1 RCT; Dumais et al. (2012)

21 vs. 24 participants

Home exercise program

WOMAC Total (16 weeks)a

44.4 (13.7)

36.2 (16.8)

NR

NR

NR

0.002

Ewart et al. (2024)22

1 RCT; Baygutalp et al. (2021)

25 vs. 25 participants

2 comparators:

  • Ozone, intra- and extra-articular with home exercise

  • Home exercise program only

WOMAC Total (6, 12 weeks)a

55.9 (17.0)

Ozone with home exercise: 58.0 (9.5)

NR

Ozone with home exercise: NR

Ozone with home exercise: NR

Ozone with home exercise:

  • 6 weeks: 0.562

  • 2 weeks: 0.096

Ewart et al. (2024)22

1 RCT; Baygutalp et al. (2021)

25 vs. 25 participants

2 comparators:

  • Ozone, intra- and extra-articular with home exercise

  • Home exercise program only

WOMAC Total (6, 12 weeks)a

55.9 (17.0)

Home exercise only: 57.6 (21.5)

NR

Home exercise only: NR

Home exercise only: NR

Home exercise only:

  • 6 weeks: 0.053

  • 2 weeks: 0.096

Ewart et al. (2024)22

1 RCT; Hashemi et al. (2015)

40 vs. 40 participants

Ozone 5 to 7 mL

WOMAC Total (3 months)

58.5 (13.3)

56.3 (11.5)

83.7 (15.3)

81.6 (13.7)

2.1 (NR)

0.173

Ewart et al. (2024)22

1 RCT; Waluyo et al. (2021)

44 vs. 32 participants

Intra-articular HA, 10 mg

WOMAC Total (12 weeks)a

36.08 (10.06)

24.81 (17.25)

19.15 (12.04)

15.86 (14.78)

3.3 (NR)

0.801

Ewart et al. (2024)22

1 RCT; Hosseini et al. (2019)

52 vs. 52 participants

Intra-articular HA 2.5 mL

Modified WOMAC Total (3 months)

52.7 (9.8)

55.9 (10.4)

83.7 (12.7)

88.5 (15.6)

−4.8 (NR)

0.001

Ewart et al. (2024)22

1 RCT; Babaeian et al. (2022)

28 vs. 26 participants

Hypertonic 2.5% saline 6 mL

  • WOMAC Total (2, 4 weeks)

  • OKS (2, 4 weeks)a

WOMAC Total: 0.52 (0.1)

0.6 (0.14)

2 weeks: 0.5 (0.11)

4 weeks: 0.5 (0.12)

2 weeks: 0.47 (0.14)

4 weeks: 0.47 (0.16)

2 weeks: 0.0 (NR)

4 weeks: 0.0 (NR)

NR

Ewart et al. (2024)22

1 RCT; Babaeian et al. (2022)

28 vs. 26 participants

Hypertonic 2.5% saline 6 mL

  • WOMAC Total (2, 4 weeks)

OKS (2, 4 weeks)a

OKS: 20.3 (7.6)

19.2 (6.5)

2 weeks: 21.1 (7.8)

4 weeks: 21.5 (7.8)

2 weeks: 21.6 (6.6)

4 weeks: 24.5 (7.2)

2 weeks: −0.5 (NR)

4 weeks: −3.0 (NR)

NR

Ewart et al. (2024)22

1 RCT; Bayat et al. (2023)

28 vs. 28 participants

Corticosteroid injections (Triamcinolone 40 mg [with 0.5% lidocaine])

WOMAC Total (1, 3 months)a

43.0 (6.3)

41.8 (7.9)

1 month: NR

3 months: NR

1 month: NR

3 months: NR

1 month: 2.02

(−1.5 to 5.6)

3 months: −9.64

(−12.0 to −6.2)

1 month: 0.262

3 months: < 0.001

Ewart et al. (2024)22

1 RCT; Rezasoltani et al. (2020)

30 vs. 30 participants

3 comparators (all with home exercise):

  • PT (TENS, therapeutic ultrasound, hotpacks)

  • Botulinum neurotoxin 100 U

  • HA 2 mL

KOOS ADL (3 months)a

39.6 (14.1)

PT: 34.7 (12.9)

NR

PT: NR

PT: NR

PT: NR

Ewart et al. (2024)22

1 RCT; Rezasoltani et al. (2020)

30 vs. 30 participants

3 comparators (all with home exercise):

  • PT (TENS, therapeutic ultrasound, hotpacks)

  • Botulinum neurotoxin 100 U

  • HA 2 mL

KOOS ADL (3 months)a

39.6 (14.1)

Botulinum neuro­toxin: 36.8 (10.0)

NR

Botulinum neurotoxin: NR

Botulinum neurotoxin: NR

Botulinum neurotoxin: NR

Ewart et al. (2024)22

1 RCT; Rezasoltani et al. (2020)

30 vs. 30 participants

3 comparators (all with home exercise):

  • PT (TENS, therapeutic ultrasound, hotpacks)

  • Botulinum neurotoxin 100 U

  • HA 2 mL

KOOS ADL (3 months)a

39.6 (14.1)

HA: 33.7 (13.6)

NR

HA: NR

HA: NR

HA: NR

Physical performance

Ewart et al. (2024)22

1 RCT; Dumais et al. (2012)

21 vs. 24 participants

Home exercise program only

TUG (16 weeks)

NR

NR

NR

NR

NR

0. 89

Ewart et al. (2024)22

1 RCT; Baygutalp et al. (2021)

25 vs. 25 participants

2 comparators:

  • Ozone, intra- and extra-articular with home exercise

  • Home exercise program only

TUG, ROM Active (6, 12 weeks)a

Physical performance TUG

11.8 (2.3)

Ozone with home exercise

13.8 (2.6)

NR

Ozone with home exercise: NR

Ozone with home exercise: NR

Ozone with home exercise:

  • 6 weeks: 0.588

  • 12 weeks: 0.102

Ewart et al. (2024)22

1 RCT; Baygutalp et al. (2021)

25 vs. 25 participants

2 comparators:

  • Ozone, intra- and extra-articular with home exercise

  • Home exercise program only

TUG, ROM Active (6, 12 weeks)a

Physical performance TUG

11.8 (2.3)

Home exercise only

12.6 (2.9)

NR

Home exercise only: NR

Home exercise only: NR

Home exercise only:

  • 6 weeks: 0.588

  • 12 weeks: 0.102

Ewart et al. (2024)22

1 RCT; Baygutalp et al. (2021)

25 vs. 25 participants

2 comparators:

  • Ozone, intra- and extra-articular with home exercise

  • Home exercise program only

TUG, ROM Active (6, 12 weeks)a

Physical performance ROM

126.0 (13.8)

Ozone with home exercise

125.8

NR

Ozone with home exercise: NR

Ozone with home exercise: NR

Ozone with home exercise

  • 6 weeks: 0.109

  • 12 weeks: 0.891

Ewart et al. (2024)22

1 RCT; Baygutalp et al. (2021)

25 vs. 25 participants

2 comparators:

  • Ozone, intra- and extra-articular with home exercise

  • Home exercise program only

TUG, ROM Active (6, 12 weeks)a

Physical performance ROM

126.0 (13.8)

Home exercise only

129.8 (10.6)

NR

Home exercise only: NR

Home exercise only: NR

Home exercise only:

  • 6 weeks: 0.109

  • 12 weeks: 0.006

Ewart et al. (2024)22

1 RCT; Rahimzadeh et al. (2014)

26 vs. 20/24 participants

2 comparators:

  • Erythropo­ietin 4,000 IU (plus 0.5% ropivacaine), fluoroscopy guided

  • Pulsed radiofre­quency waves, fluoroscopy guided

ROM (2, 4, 12 weeks)

101.0 (1.4)

Erythro­poietin

98.1 (1.6)

2 weeks: 106.0 (1.4)

4 weeks: 110.0 (1.3)

12 weeks: 113.0 (2.2)

Erythropoietin:

  • 2 weeks: 124.0 (1.5)

  • 4 weeks: 124.0 (1.4)

  • 12 weeks: 123.0 (1.5)

Erythropoietin:

  • 2 weeks: −18.0 (NR)

  • 4 weeks: −14.0 (NR)

  • 12 weeks: −10.0 (NR)

Erythro­poietin: NR

Ewart et al. (2024)22

1 RCT; Rahimzadeh et al. (2014)

26 vs. 20/24 participants

2 comparators:

  • Erythropo­ietin 4,000 IU (plus 0.5% ropivacaine), fluoroscopy guided

  • Pulsed radiofre­quency waves, fluoroscopy guided

ROM (2, 4, 12 weeks)

101.0 (1.4)

Pulsed radio frequency

95.0 (2.0)

2 weeks: 106.0 (1.4)

4 weeks: 110.0 (1.3)

12 weeks: 113.0 (2.2)

Pulsed radio frequency:

  • 2 weeks: 105.0 (2.1)

  • 4 weeks: 110.0 (2.1)

  • 12 weeks: 113.0 (2.2)

Pulsed radio frequency:

  • 2 weeks: 1.0 (NR)

  • 4 weeks: 0.0 (NR)

  • 12 weeks: 0.0 (NR)

Pulsed radio frequency: NR

Pain intensity or severity

Ewart et al. (2024)22

SR with MA (3 RCTs)

81 vs. 79 participants

PT or home exercise program

VAS at short-term follow-up (1 to 1.5 month)

NR

NR

NR

NR

SMD = −0.76

(−1.59 to 0.07)

NR

Ewart et al. (2024)22

SR with MA (3 RCTs)

81 vs. 79 participants

PT or home exercise program

VAS at medium-term follow-up (3 to 4 months)

NR

NR

NR

NR

SMD = −1.42

(−2.19 to −0.65)

NR

Ewart et al. (2024)22

1 RCT; Babaeian et al. (2022)

28 vs. 26 participants

Hypertonic 2.5% saline 6 mL

VAS (2, 4 weeks)

77.5 (19.8)

83.2 (14.6)

2 weeks: 71.0 (20.4)

4 weeks: 68.2 (19.9)

2 weeks: 75.5 (18.9)

4 weeks: 70.0 (18.5)

2 weeks: −4.5

4 weeks: −1.8

2 weeks: NR

4 weeks: NR

Ewart et al. (2024)22

1 RCT; Waluyo et al. (2021)

44 vs. 32 participants

Intra-articular HA, 10 mg

NRS (12 weeks)

4.85 (1.71)

3.48 (1.53)

1.46 (1.3)

1.86 (1.52)

−0.4 (NR)

0.042

Ewart et al. (2024)22

1 RCT; Rezasoltani et al. (2020)

30 vs. 30 participants

3 comparators (all with home exercise):

  • PT (TENS, therapeutic ultrasound, hotpacks)

  • Botulinum neurotoxin 100 U

  • HA 2 mL

VAS (1 week, 1, 3 months)a

6.5 (1.3)

PT: 7.2 (1.1)

1 week: 2.8 (NR)

1 month: 2.8 (NR)

3 months: 2.5 (NR)

PT:

  • 1 week: 4.6 (NR)

  • 1 month: 3.7 (NR)

  • 3 months: 3.8 (NR)

PT:

  • 1 week: −1.8 (NR)

  • 1 month: −0.9 (NR)

  • 3 months: −3.1 (NR)

PT:

  • 1 week: < 0.001

  • 1 month: < 0.001

  • 3 months: < 0.001

Ewart et al. (2024)22

1 RCT; Rezasoltani et al. (2020)

30 vs. 30 participants

3 comparators (all with home exercise):

  • PT (TENS, therapeutic ultrasound, hotpacks)

  • Botulinum neurotoxin 100 U

  • HA 2 mL

VAS (1 week, 1, 3 months)a

6.5 (1.3)

Botulinum neuro­toxin: 6.6 (1.6)

1 week: 2.8 (NR)

1 month: 2.8 (NR)

3 months: 2.5 (NR)

Botulinum neurotoxin:

  • 1 week: 3.4 (NR)

  • 1 month: 3.1 (NR)

  • 3 months: 2.3 (NR)

Botulinum neurotoxin:

  • 1 week: −0.6 (NR)

  • 1 month: −0.3 (NR)

  • 3 months: 0.2 (NR)

Botulinum neurotoxin:

  • 1 week: < 0.001

  • 1 month: < 0.001

  • 3 months: < 0.001

Ewart et al. (2024)22

1 RCT; Rezasoltani et al. (2020)

30 vs. 30 participants

3 comparators (all with home exercise):

  • PT (TENS, therapeutic ultrasound, hotpacks)

  • Botulinum neurotoxin 100 U

  • HA 2 mL

VAS (1 week, 1, 3 months)a

6.5 (1.3)

HA: 6.7 (0.7)

1 week: 2.8 (NR)

1 month: 2.8 (NR)

3 months: 2.5 (NR)

HA:

  • weeks: 4.9 (NR)

  • 1 month: 4.8 (NR)

  • 3 months: 5.7 (NR)

HA:

  • 1 week: −2.1 (NR)

  • 1 month: −2.0 (NR)

  • 3 months: −3.2 (NR)

HA:

  • 1 week: < 0.001

  • 1 month: < 0.001

  • 3 months: < 0.001

Ewart et al. (2024)22

1 RCT; Rahimzadeh et al. (2014)

26 vs. 20/24 participants

2 comparators:

  • Erythro­poietin 4,000 IU (+ 0.5% ropivacaine), fluoroscopy guided

  • Pulsed radiofre­quency waves, fluoroscopy guided

VAS (2, 4, 12 weeks)

7.1 (1.0)

Erythro­poietin: 6.7 (1.0)

2 weeks: 4.5 (1.4)

4 weeks: 4.7 (1.4)

12 weeks: 5.5 (1.6)

Erythropoietin:

  • 2 weeks: 3.2 (1.1)

  • 4 weeks: 3.2 (0.9)

  • 12 weeks: 3.5 (1.2)

Erythropoietin:

  • 2 weeks: 1.3 (NR)

  • 4 weeks: 1.5 (NR)

  • 12 weeks: 2.0 (NR)

Erythro­poietin: NR

Ewart et al. (2024)22

1 RCT; Rahimzadeh et al. (2014)

26 vs. 20/24 participants

2 comparators:

  • Erythro­poietin 4,000 IU (+ 0.5% ropivacaine), fluoroscopy guided

  • Pulsed radiofre­quency waves, fluoroscopy guided

VAS (2, 4, 12 weeks)

7.1 (1.0)

Pulsed radio­frequency waves: 7.1 (1.4)

2 weeks: 4.5 (1.4)

4 weeks: 4.7 (1.4)

12 weeks: 5.5 (1.6)

Pulsed radiofrequency waves:

  • 2 weeks: 3.3 (2.0)

  • 4 weeks: 3.9 (1.7)

  • 12 weeks: 5.5 (1.9)

Pulsed radiofre­quency waves:

  • 2 weeks: 1.2 (NR)

  • 4 weeks: 0.8 (NR)

  • 12 weeks: 0.0 (NR)

Pulsed radiofre­quency waves: NR

Health-related quality of life

Ewart et al. (2024)22

1 RCT; Ozturk et al. (2023)

31 vs. 32 participants

Hot packs + home exercise program

SF-36 Physical Score, SF-36 Mental score (12 weeks)

NR

Physical: NR

NR

NR

NR

NR

Ewart et al. (2024)22

1 RCT; Ozturk et al. (2023)

31 vs. 32 participants

Hot packs + home exercise program

SF-36 Physical Score, SF-36 Mental score (12 weeks)

NR

Mental: NR

NR

NR

NR

NR

Ewart et al. (2024)22

1 RCT; Sert et al. (2020)

22 vs. 22 participants

Home exercise

SF-36 Physical score, SF-36 Mental score (6, 18 weeks)

45.4 (10.9)

Physical: 35.0 (9.3)

6 weeks: 52.7 (9.1)

18 weeks: 53.5 (6.8)

6 weeks: 41.2 (10.4)

18 weeks: 41.1 (11.7)

6 weeks: 0.0

18 weeks: 7.4

6 weeks: NR

18 weeks: 0.016

Ewart et al. (2024)22

1 RCT; Sert et al. (2020)

22 vs. 22 participants

Home exercise

SF-36 Physical score, SF-36 Mental score (6, 18 weeks)

45.4 (10.9)

Mental: 44.1 (8.7)

6 weeks: 52.7 (9.1)

18 weeks: 53.5 (6.8)

6 weeks: 45.9 (10.0)

18 weeks: 49.6 (10.9)

6 weeks: 6.8

18 weeks: 3.9

6 weeks: NR

18 weeks: NR

ADL = Activities of Daily Living; CI = confidence interval; HA = hyaluronic acid; KOOS = Knee Injury and Osteoarthritis Outcome Score; MA = meta-analysis; NR = not reported; NRS = numerical rating scale; OKS = Oxford Knee Score; PRP = Platelet-Rich Plasma; PT = physical therapy; RCT = randomized controlled trial; ROM = range of motion; SD = standard deviation; SF-36 = Short Form (36) Health Survey; SMD = standardized mean difference; SR = systematic review; TENS = transcutaneous electrical nerve stimulation; TUG = timed up and go; VAS = visual analogue scale; vs. = versus; WOMAC = Western Ontario and McMaster Universities Arthritis Index.

aAdditional results related to this outcome measure are available in the original SR.22

Table 10: Summary of Findings by Outcome and Comparator — Plantar Fasciitis; Dextrose Prolotherapy vs. Placebo

Citation

Evidence source, number of participants (intervention vs. comparator)

Comparator, outcome measure

Baseline, mean (SD)

Follow-up, mean (SD)

Relative effect, mean difference (95% CI)

P value (between groups)

Intervention

Comparator

Intervention

Comparator

Pain-related functioning

Ewart et al. (2024)22

1 RCT; Mansiz-Kaplan et al. (2020)

32 vs. 33 participants

Normal saline

Modified FFI‑Total (7, 15 weeks)a

202 (32.4)

190 (38.6)

7 weeks: 20.1 (28.9)

15 weeks: 14.4 (23.1)

7 weeks: 113.4 (50.8)

15 weeks: 118.9 (47.6)

7 weeks: −93.3 (NR)

15 weeks: −104.5 (NR)

7 weeks: < 0.001

15 weeks: < 0.001

Ewart et al. (2024)22

1 RCT; Umay Altas et al. (2018)

15 vs. 15 participants

Normal saline

FFI-Total (3 months)a

NR

NR

NR

NR

Median change (range) = 34.7 (23.2 to 45.3)

0.001

Pain intensity or severity

Ewart et al. (2024)22

1 RCT; Mansiz-Kaplan et al. (2020)

32 vs. 33 participants

Normal saline

VAS during activity (7, 15 weeks)a

NR

NR

NR

NR

NR

NR

Ewart et al. (2024)22

1 RCT; Umay Altas et al. (2018)

15 vs. 15 participants

Normal saline

VAS (3 months)

Median (range): 8.0 (5.0 to10.0)

Median (range): 6.0 (4.0 to 9.0)

NR

NR

NR

NR

CI = confidence interval; FFI = foot function index; NR = not reported; RCT = randomized controlled trial; SD = standard deviation; SR = systematic review; VAS = visual analogue scale; vs. = versus.

aAdditional results related to this outcome measure are available in the original SR.22

Table 11: Summary of Findings by Outcome and Comparator — Plantar Fasciitis; Dextrose Prolotherapy vs. Other Comparators

Citation

Evidence source, number of participants (intervention vs. comparator)

Comparator, outcome measure

Baseline, mean (SD)

Follow-up, mean (SD)

Relative effect, mean difference (95% CI)

P value (between groups)

Intervention

Comparator

Intervention

Comparator

Pain-related functioning

Qafesha et al. (2026)24

SR with MA (1 RCTs, 1 non‑RCT)

45 vs. 45 participants

Corticosteroid injections

Walking VAS change (0.5 month)

NR

NR

NR

NR

1.85

(0.68 to 3.02)

0.002

Qafesha et al. (2026)24

SR with MA (1 RCTs, 1 non‑RCT)

45 vs. 45 participants

Corticosteroid injections

Walking VAS change (3 months)

NR

NR

NR

NR

−0.44

(−0.96 to 0.08)

0.10

Ewart et al. (2024)22

1 RCT; Asheghan et al. (2021)

31 vs. 31 participants

ESWT, 2,000 shocks (2 bars pressure, 10 Hz) to heel

FAAM-ADL (6, 12 weeks)

FAAM-Sport (6, 12 weeks)

FAAM-ADL:

72.4 (12.8)

74.2 (10.2)

6 weeks: 87.5 (8.7)

12 weeks: 90.0 (8.9)

6 weeks: 88.3 (7.2)

12 weeks: 91.3 (6.8)

6 weeks: −0.8 (NR)

12 weeks: −1.3 (NR)

NR

Ewart et al. (2024)22

1 RCT; Asheghan et al. (2021)

31 vs. 31 participants

ESWT, 2,000 shocks (2 bars pressure, 10 Hz) to heel

FAAM-ADL (6, 12 weeks)

FAAM-Sport (6, 12 weeks)

FAAM-Sport:

70.1 (11.8)

72.6 (12.3)

6 weeks: 83.3 (10.8)

12 weeks: 85.8 (9.3)

6 weeks: 88.7 (11.1)

12 weeks: 92.3 (10.2)

6 weeks: −5.4 (NR)

12 weeks: −6.5 (NR)

NR

Ewart et al. (2024)22

1 RCT; Kesikburun et al. (2022)

14 vs. 15 participants

ESWT, 1,800 to 2,000 shocks (0.20 to 0.30 mJ/mm2, 4 to 6 Hz) to heel and 3,000 to 3,500 shocks (1.8 to 3.0 bars pressure, 15 to 21 Hz) to foot muscles

FFI (6, 12 weeks)

70.5 (15.4)

62.7 (12.2)

6 weeks: 43.6 (32.9)

12 weeks: 29.3 (27.7)

6 weeks: 42.1 (21.5)

12 weeks: 27.4 (25.8)

6 weeks: 1.5 (NR)

12 weeks: 1.9 (NR)

NR

Ewart et al. (2024)22

1 RCT; Ersen et al. (2018)

29 vs. 31 participants

PT and home exercises

FFI-Total (21, 42, 90, 360 days)a

57.7 (13.6)

56.9 (12.8)

21 days: 52.7 (15.3)

42 days: 38.6 (15.8)

90 days: 31.1 (17.0)

360 days: 26.0 (20.3)

21 days: 53.9 (14.0)

42 days: 51.3 (16.9)

90 days: 47.8 (20.7)

360 days: 34.3 (25.2)

21 days: 53.9 (14.0)

42 days: 51.3 (16.9)

90 days: 47.8 (20.7)

360 days: 34.3 (25.2)

21 days: 0.235

42 days: < 0.001

90 days: < 0.001

360 days: 0.113

Ewart et al. (2024)22

1 RCT; Karakilic et al. (2003)

Participants NR

Phonophoresis, 1.5W/cm2 1 MHz

FFI-Total (1, 3 months)a

61.8 (9.1)

63.0 (9.0)

1 month: 27.0 (20.7)

3 months: 27.9 (21.8)

1 month: 27.9 (20.6)

3 months: 35.5 (25.2)

1 month: −0.9 (NR)

3 months: −7.6 (NR)

NR

Ewart et al. (2024)22

1 RCT; Kim et al. (2014)

11 vs. 10 participants

PRP approximately 2 mL, ultrasound guided

FFI-Total (10, 28 weeks)a

132.5 (31.1)

151.5 (37.9)

10 weeks: 123.7 (47.4)

28 weeks: 97.7 (52.5)

10 weeks: 123.8 (45.4)

28 weeks: 81.6 (55.3)

10 weeks: −0.1 (NR)

28 weeks: 16.1 (NR)

10 weeks: 0.88

28 weeks: 0.60

Physical performance

Qafesha et al. (2026)24

SR with MA (4 RCTs)

128 vs. 126 participants

Corticosteroid injections

FFI change (1 month)

NR

NR

NR

NR

18.81

(0.06 to 37.55)

0.05

Qafesha et al. (2026)24

SR with MA (4 RCTs, 1 non-RCT)

128 vs. 126 participants

Corticosteroid injections

FFI change (3 months)

NR

NR

NR

NR

- 5.47

(−9.03 to −1.92)

0.003

Pain intensity or severity

Qafesha et al. (2026)24

SR with MA (3 RCTs)

88 vs. 86 participants

Corticosteroid injectionsb

General VAS score change (1 month)

NR

NR

NR

NR

1.85 (0.05 to 3.64)

0.04

Qafesha et al. (2026)24

SR with MA (3 RCTs, 1 non-RCT)

118 vs. 116 participants

Corticosteroid injectionsb

General VAS score change (3 months)

NR

NR

NR

NR

- 0.20 (−1.17 to 0.77)

0.68

Qafesha et al. (2026)24

SR with MA (2 RCTs, 1 non‑RCT)

45 vs. 45 participants

Corticosteroid injections

Morning VAS score change (0.5 to 1 month)

NR

NR

NR

NR

1.26 (0.49 to 2.02)

0.001

Qafesha et al. (2026)24

SR with MA (2 RCTs, 1 non‑RCT)

85 vs. 85 participants

Corticosteroid injections

Morning VAS score change (3 months)

NR

NR

NR

NR

0.10 (−0.29 to 0.50)

0.61

Ewart et al. (2024)22

1 RCT; Asheghan et al. (2021)

31 vs. 31 participants

ESWT, 2,000 shocks (2 bars pressure, 10 Hz) to heel

VAS (6, 12 weeks)

74.7 (11.2)

72.3 (13.2)

6 weeks: 53.3 (10.1)

12 weeks: 44.2 (9.5)

6 weeks: 56.6 (12.5)

12 weeks: 40.8 (10.3)

6 weeks: −3.3 (NR)

12 weeks: 3.4 (NR)

6 weeks: NR

12 weeks: NR

Ewart et al. (2024)22

1 RCT; Kesikburun et al. (2022)

14 vs. 15 participants

ESWT, 1,800 to 2,000 shocks (0.20 to 0.30 mJ/mm2, 4 to 6 Hz) to heel and 3,000 to 3,500 shocks (1.8 to 3.0 bars pressure, 15 to 21 Hz) to foot muscles

VAS (6, 12 weeks)

80.9 (18.1)

74.6 (14.8)

6 weeks: 48.1 (37.9)

12 weeks: 34.0 (34.1)

6 weeks: 48.9 (23.4)

12 weeks: 33.9 (32.2)

6 weeks: −0.8 (NR)

12 weeks: 0.1 (NR)

6 weeks: NR

12 weeks: NR

Ewart et al. (2024)22

1 RCT; Ersen et al. (2018)

29 vs. 31 participants

PT and home exercises

VAS (21, 42, 90, 360 days)

6.9 (1.5)

6.7 (1.4)

21 days: 5.9 (1.9)

42 days: 4.3 (2.2)

90 days: 3.1 (2.4)

360 days: 2.4 (2.6)

21 days: 6.0 (1.5)

42 days: 5.7 (2.1)

90 days: 5.0 (2.8)

360 days: 3.7 (3.0)

21 days: −0.1 (NR)

42 days: −1.4 (NR)

90 days: −1.9 (NR)

360 days: −1.3 (NR)

21 days: 0.319

42 days: 0.001

90 days: 0.002

360 days: 0.042

Health-related quality of life

Ewart et al. (2024)22

1 RCT; Karakilic et al. (2003)

Participants NR

Phonophoresis, 1.5W/cm2 1 MHz

QoL SF-36 General Health (1, 3 months)a

41.0 (16.3)

36.0 (15.1)

1 month: 56.7 (15.9)

3 months: 56.9 (17.2)

1 month: 48.0 (15.2)

3 months: 44.9 (15.5)

1 month: 8.7 (NR)

3 months: 12.0 (NR)

NR

CI = confidence interval; ESWT = extracorporeal shock wave therapy; FAAM = Foot and Ankle Ability Measure; FAOS = Foot and Ankle Outcome Score; FFI = foot function index; MA = meta-analysis; NR = not reported; PRP = Platelet-Rich Plasma; PT = physical therapy; QoL = quality of life; RCT = randomized controlled trial; SD = standard deviation; SF-36 = Short Form (36) Health Survey; SMD = standardized mean difference; SR = systematic review; VAS = visual analogue scale; vs. = versus.

aAdditional results related to this outcome measure are available in the original SR.22

bSubgroup analysis separating studies based on their injection guidance method [ultrasound‐guided studies (2 studies) and palpation‐guided studies (2 studies)] is also available for these outcomes in this publication.24

Table 12: Summary of Findings by Outcome and Comparator — Shoulder Pain (Mixed Rotator Cuff Pathology and Subacromial Bursitis); Dextrose Prolotherapy vs. Placebo

Citation

Evidence source, number of participants (intervention vs. comparator)

Comparator, outcome measure

Baseline, mean (SD)

Follow-up, mean (SD)

Relative effect, mean difference (95% CI)

P value (between groups)

Intervention

Comparator

Intervention

Comparator

Pain-related functioning

Ewart et al. (2024)22

SR with MA (3 RCTs)

74 vs. 75 participants

Normal saline

DASH, SPADI, ASES or WORC scores at short-term follow-up (3 to 6 weeks)

NR

NR

NR

NR

SMD = - 0.29

(−1.15 to 0.57)

NR

Ewart et al. (2024)22

SR with MA (3 RCTs)

74 vs. 75 participants

Normal saline

DASH, SPADI, ASES or WORC scores at medium-term follow-up (3 months)

NR

NR

NR

NR

SMD = - 0.30

(−1.01 to 0.41)

NR

Physical performance

Ewart et al. (2024)22

1 RCT; Chang et al. (2021)

25 vs. 25 participants

Normal saline

ROM: Forward Flexion, Abduction (1 week, 1, 3 months)

Flexion:

146.8 (23.04)

144.60 (25.66)

1 week: 160.8 (17.0)

1 month: 163.6 (14.2)

3 months: 168.8 (11.8)

1 week: 150.2 (24.0)

1 month: 157.0 (20.2)

3 months: 160.2 (22.80)

1 week: 10.6 (NR)

1 month: 6.6 (NR)

3 months: 8.6 (NR)

NR

Ewart et al. (2024)22

1 RCT; Chang et al. (2021)

25 vs. 25 participants

Normal saline

ROM: Forward Flexion, Abduction (1 week, 1, 3 months)

Adduction:

117.4 (23.04)

115.60 (27.20)

1 week: 138.4 (32.2)

1 month: 138.6 (31.5)

3 months: 153.0 (29.5)

1 week: 127.8 (31.3)

1 month: 137.6 (30.7)

3 months: 144.0 (31.3)

1 week: 10.6 (NR)

1 month: 1.0 (NR)

3 months: 9 (NR)

NR

Ewart et al. (2024)22

1 RCT; Sam et al. (2023)

26 vs. 25 participants

Normal saline

ROM: Forward Flexion, Abduction, Adduction, External Rotation, Internal Rotation (12 weeks)

Flexion:

129.60 (16.10)

123.87 (19.64)

151.05 (29.70)

140.75 (31.47)

10.3 (NR)

0.31

Ewart et al. (2024)22

1 RCT; Sam et al. (2023)

26 vs. 25 participants

Normal saline

ROM: Forward Flexion, Abduction, Adduction, External Rotation, Internal Rotation (12 weeks)

Extension:

45.92 (16.10)

44.75 (18.99)

53.16 (11.81)

47.75 (10.57)

5.41 (NR)

0.13

Ewart et al. (2024)22

1 RCT; Sam et al. (2023)

26 vs. 25 participants

Normal saline

ROM: Forward Flexion, Abduction, Adduction, External Rotation, Internal Rotation (12 weeks)

Abduction:

125.00 (16.10)

117.13 (24.00)

153.68 (26.71)

140.50 (32.96)

13.18 (NR)

0.25

Ewart et al. (2024)22

1 RCT; Sam et al. (2023)

26 vs. 25 participants

Normal saline

ROM: Forward Flexion, Abduction, Adduction, External Rotation, Internal Rotation (12 weeks)

Adduction:

47.63 (16.10)

49.50 (22.09)

57.37 (10.46)

56.00 (7.71)

1.37 (NR)

0.87

Ewart et al. (2024)22

1 RCT; Sam et al. (2023)

26 vs. 25 participants

Normal saline

ROM: Forward Flexion, Abduction, Adduction, External Rotation, Internal Rotation (12 weeks)

External rotation:

43.68 (16.10)

46.75 (26.03)

66.58 (21.67)

55.00 (22.77)

11.58 (NR)

0.11

Ewart et al. (2024)22

1 RCT; Sam et al. (2023)

26 vs. 25 participants

Normal saline

ROM: Forward Flexion, Abduction, Adduction, External Rotation, Internal Rotation (12 weeks)

Internal rotation:

61.05 (16.10)

53.13 (25.34)

75.00 (12.91)

71.25 (14.13)

3.75 (NR)

0.42

Pain intensity or severity

Ewart et al. (2024)22

SR with MA (3 RCTs)

74 vs. 75 participants

Normal saline

VAS or NRS scores at short-term follow-up (3 to 6 weeks)

NR

NR

NR

NR

SMD = - 0.33

(−1.47 to 0.81)

NR

Ewart et al. (2024)22

SR with MA (3 RCTs)

74 vs. 75 participants

Normal saline

VAS or NRS scores at medium-term follow-up (3 to 4 months)

NR

NR

NR

NR

SMD = - 0.62

(−3.18 to 1.94)

NR

Ewart et al. (2024)22

1 RCT; Bertrand et al. (2016)

27 vs. 24/26 participants

2 comparators, both with PT/home exercise:

  • Normal saline volume variable (with 0.1% lidocaine) using same injection procedure as dextrose

  • Normal saline volume variable (with 0.1% lidocaine) superficial injections only

VAS (3, 9 months)

7.3 (0.4)

Normal Saline (same injection technique): 6.9 (0.5)

NR

Normal Saline (same injection technique): NR

Normal Saline (same injection technique): NR

Normal Saline (same injection technique): NR

Ewart et al. (2024)22

1 RCT; Bertrand et al. (2016)

27 vs. 24/26 participants

2 comparators, both with PT/home exercise:

  • Normal saline volume variable (with 0.1% lidocaine) using same injection procedure as dextrose

  • Normal saline volume variable (with 0.1% lidocaine) superficial injections only

VAS (3, 9 months)

7.3 (0.4)

Normal Saline (superficial injection only): 6.9 (0.4)

NR

Normal Saline (superficial injection only): NR

Normal Saline (superficial injection only): NR

Normal Saline (superficial injection only): NR

ASES = American Shoulder and Elbow Surgeons Standardized Shoulder Assessment; DASH = disability of the arm, shoulder, and hand; MA = meta-analysis; NR = not reported; NRS = numerical rating scale; PT = physical therapy; RCT = randomized controlled trial; ROM = range of motion; SPADI = shoulder pain and disability index; SMD = standardized mean difference; SR = systematic review; VAS = visual analogue scale; vs. = versus; WORC = Western Ontario Rotator Cuff Index.

Table 13: Summary of Findings by Outcome and Comparator — Shoulder Pain (Mixed Rotator Cuff Pathology and Subacromial Bursitis); Dextrose Prolotherapy vs. Other Comparators

Citation

Evidence source, number of participants (intervention vs. comparator)

Comparator, outcome measure

Baseline, mean (SD)

Follow-up, mean (SD)

Relative effect, mean difference (95% CI)

P value (between groups)

Intervention

Comparator

Intervention

Comparator

Pain-related functioning

Thamrongskulsiri et al. (2025)26

1 retrospective case-control study; Lee et al. (2015)

57 vs. 53 participants

Active control

Both groups received PT (regular exercise education by physical therapists)

SPADI (12 months)

NR

NR

43.8 (11.6)

51.1 (14.4)

−7.30

(−12.21 to −2.39)

NR

Ewart et al. (2024)22

SR with MA (3 RCTs)

75 vs. 72 participants

Corticosteroid injection

SPADI or ASES and WORC scores at short-term follow-up (3 to 6 weeks)

NR

NR

NR

NR

SMD = 0.86

(−0.32 to 2.04)

NR

Ewart et al. (2024)22

SR with MA (3 RCTs)

75 vs. 72 participants

Corticosteroid injection

SPADI or ASES and WORC scores at medium-term follow-up (12 weeks)

NR

NR

NR

NR

SMD = 0.58

(−2.19 to 3.36)

NR

Ewart et al. (2024)22

1 RCT; Mofrad et al. (2021)

33 vs. 33 participants

PT (hot packs, TENS, therapeutic ultrasound) with home exercise program

Modified SPADI total (2 weeks, 3 months)a

78.1 (9.0)

62.6 (5.8)

2 weeks: 30.9 (24.5 to 36.2)

3 months: 35.7 (30.0 to 41.0)

2 weeks: 34.3 (32.0 to 37.2)

3 months: 31.3 (30.1 to 32.6)

2 weeks: −3.4 (NR)

3 months: 4.4 (NR)

NR

Ewart et al. (2024)22

1 RCT; Bertrand et al. (2016)

27 vs. 24/26 participants

2 comparators, both with PT/home exercise:

  • Normal saline volume variable (with 0.1% lidocaine) using same injection procedure as dextrose

  • Normal saline volume variable (with 0.1% lidocaine) superficial injections only

VAS (3, 9 months)

74.76 (18.54)

68.62 (20.40)

3 weeks: 53.17 (16.44)

6 weeks: 31.30 (14.19)

12 weeks: 16.12 (12.82)

1 year: 7.66 (10.64)

3 weeks: 58.70 (18.49)

6 weeks: 41.97 (16.42)

12 weeks: 37.25 (20.32)

1 year: 34.94 (10.64)

3 weeks: −5.53 (NR)

6 weeks: −10.67 (NR)

12 weeks: −21.13 (NR)

1 year: −27.28 (NR)

3 weeks: 0.12

6 weeks: 0.01

12 weeks: < 0.001

1 year: < 0.001

Physical performance

Thamrongskulsiri et al. (2025)26

1 retrospective case-control study; Lee et al. (2015)

57 vs. 53 participants

Active control

Both groups received PT (regular exercise education by physical therapists)

ROM: Forward Flexion, Abduction,

Internal rotation,

External rotation (12 months)

Flexion:

NR

NR

169.1 (11.7)

163.1 (16.9)

6.00 (0.53 to 11.47)

NR

Thamrongskulsiri et al. (2025)26

1 retrospective case-control study; Lee et al. (2015)

57 vs. 53 participants

Active control

Both groups received PT (regular exercise education by physical therapists)

ROM: Forward Flexion, Abduction,

Internal rotation,

External rotation (12 months)

Abduction:

NR

NR

165.5 (16.7)

153.1 (27.1)

12.40 (3.91 to 20.89)

NR

Thamrongskulsiri et al. (2025)26

1 retrospective case-control study; Lee et al. (2015)

57 vs. 53 participants

Active control

Both groups received PT (regular exercise education by physical therapists)

ROM: Forward Flexion, Abduction,

Internal rotation,

External rotation (12 months)

Internal rotation:

NR

NR

58.3 (19.8)

54.9 (19.6)

3.40 (−3.97 to 10.77)

NR

Thamrongskulsiri et al. (2025)26

1 retrospective case-control study; Lee et al. (2015)

57 vs. 53 participants

Active control

Both groups received PT (regular exercise education by physical therapists)

ROM: Forward Flexion, Abduction,

Internal rotation,

External rotation (12 months)

External rotation:

NR

NR

86.8 (13.9)

81 (14.1)

5.80 (0.56 to 11.04)

NR

Ewart et al. (2024)22

1 RCT; Seven et al. (2017)

60 vs. 60 participants

PT (stretching and exercises in clinic)

ROM: Forward Flexion, Abduction,

Internal rotation,

External rotation (1 year)

Forward Flexion: 126.89 (40.89)

133.75 (34.84)

176.57 (9.50)

166.36 (16.95)

−7.9 (NR)

< 0.001

Ewart et al. (2024)22

1 RCT; Seven et al. (2017)

60 vs. 60 participants

PT (stretching and exercises in clinic)

ROM: Forward Flexion, Abduction,

Internal rotation,

External rotation (1 year)

Abduction: 125.96 (40.89)

128.52 (34.54)

175.26 (12.15)

164.65 (17.92)

10.61 (NR)

0.001

Ewart et al. (2024)22

1 RCT; Seven et al. (2017)

60 vs. 60 participants

PT (stretching and exercises in clinic)

ROM: Forward Flexion, Abduction,

Internal rotation,

External rotation (1 year)

Internal rotation: 59.73 (40.89)

56.47 (15.64)

68.77 (4.25)

66.02 (7.11)

2.75 (NR)

0.02

Ewart et al. (2024)22

1 RCT; Seven et al. (2017)

60 vs. 60 participants

PT (stretching and exercises in clinic)

ROM: Forward Flexion, Abduction,

Internal rotation,

External rotation (1 year)

External rotation: 77.19 (40.89)

79.31 (17.30)

88.94 (4.09)

86.59 (9.69)

2.35 (NR)

0.10

Ewart et al. (2024)22

1 RCT; Lin et al. (2023)

28 vs. 26 participants

Corticosteroid injections (Triamcinolone 40 mg)

ROM: Forward Flexion, Abduction, External Rotation, Internal Rotation (12 weeks)

Flexion:

144.6 (9.5)

142.8 (10.6)

140.5 (12.8)

157.2 (7.1)

−16.7 (NR)

< 0.001

Ewart et al. (2024)22

1 RCT; Lin et al. (2023)

28 vs. 26 participants

Corticosteroid injections (Triamcinolone 40 mg)

ROM: Forward Flexion, Abduction, External Rotation, Internal Rotation (12 weeks)

Abduction:

137.3 (9.5)

136.3 (14.1)

133.9 (15.2)

157.5 (12.4)

−23.6 (NR)

< 0.001

Ewart et al. (2024)22

1 RCT; Lin et al. (2023)

28 vs. 26 participants

Corticosteroid injections (Triamcinolone 40 mg)

ROM: Forward Flexion, Abduction, External Rotation, Internal Rotation (12 weeks)

Internal rotation:

44.6 (9.5)

43.8 (9.8)

45.4 (6.7)

54.2 (4.4)

−8.8 (NR)

< 0.001

Ewart et al. (2024)22

1 RCT; Lin et al. (2023)

28 vs. 26 participants

Corticosteroid injections (Triamcinolone 40 mg)

ROM: Forward Flexion, Abduction, External Rotation, Internal Rotation (12 weeks)

External rotation:

57.9 (9.5)

55.4 (11.0)

53.6 (4.9)

61.5 (5.1)

−16.7 (NR)

< 0.001

Pain intensity or severity

Thamrongskulsiri et al. (2025)26

1 retrospective case-control study; Lee et al. (2015)

57 vs. 53 participants

Active control

Both groups received PT (regular exercise education by physical therapists)

VAS for pain 12 months)

NR

NR

2.7 (1)

4.6 (1.4)

−1.90 (−2.36 to −1.44)

NR

Ewart et al. (2024)22

SR with MA (3 RCTs)

75 vs. 72 participants

Corticosteroid injection

VAS score at short-term follow-up (3 to 6 weeks)

NR

NR

NR

NR

SMD = 0.85

(−0.36 to 2.06)

NR

Ewart et al. (2024)22

SR with MA (3 RCTs)

75 vs. 72 participants

Corticosteroid injection

VAS score at medium-term follow-up (3 months)

NR

NR

NR

NR

SMD = 0.22

(−0.68 to 1.13)

NR

Health-related quality of life

Ewart et al. (2024)22

1 RCT; Seven et al. (2017)

60 vs. 60 participants

PT (stretching and exercises in clinic)

WORC (3,

6, 12 weeks, 1 year)

32.21 (17.49)

37.77 (16.03)

3 weeks: 52.25 (16.43)

6 weeks: 72.07 (14.48)

12 weeks: 84.98 (12.13)

1 year: 90.37 (10.12)

3 weeks: 46.59 (15.28)

6 weeks: 59.98 (16.03)

12 weeks: 66.14 (17.11)

1 year: 69.08 (10.12)

3 weeks: 5.66 (NR)

6 weeks: 12.09 (NR)

12 weeks: 18.84 (NR)

1 year: 21.29 (NR)

3 weeks: 0.08

6 weeks: < 0.001

12 weeks: < 0.001

1 year: < 0.001

ASES = American Shoulder and Elbow Surgeons Standardized Shoulder Assessment; DASH = disability of the arm, shoulder, and hand; MA = meta-analysis; NR = not reported; NRS = numerical rating scale; PT = physical therapy; RCT = randomized controlled trial; ROM = range of motion; SPADI = shoulder pain and disability index; SMD = standardized mean difference; SR = systematic review; TENS = transcutaneous electrical nerve stimulations; VAS = visual analogue scale; vs. = versus; WORC = Western Ontario Rotator Cuff Index.

aAdditional results related to this outcome measure are available in the original SR.22

Table 14: Summary of Findings by Outcome and Comparator — Shoulder Pain (Supraspinatus Tendinopathy Only); Dextrose Prolotherapy vs. Placebo or Other Comparator

Citation

Evidence source, number of participants (intervention vs. comparator)

Comparator, outcome measure

Baseline, mean (SD)

Follow-up, mean (SD)

Relative effect, mean difference (95% CI)

P value (between groups)

Intervention

Comparator

Intervention

Comparator

Pain-related functioning

Ewart et al. (2024)22

1 RCT; Lin et al. (2022)

29 vs. 28 participants

Normal saline (volume NR) in supraspinatus tendon insertion site, ultrasound guided

SPADI (2, 6, 12 weeks)

54.8 (10.7)

57.5 (12.9)

2 weeks: 43.2 (12.0)

6 weeks: 50.5 (14.3)

12 weeks: 48.5 (16.0)

2 weeks: 52.9 (16.1)

6 weeks: 51.3 (16.1)

12 weeks: 49.3 (14.5)

2 weeks: −9.7 (NR)

6 weeks: −0.80 (NR)

12 weeks: −0.80 (NR)

2 weeks: 0.01

6 weeks: 0.83

12 weeks: 0.85

Ewart et al. (2024)22

1 RCT; Abd Karim et al. (2023)

32 vs. 32 participants

PRP 2 mL in the lesion, ultrasound-guided; and home exercise program

SPADI (3, 6 weeks, 3, 6 months)

43.02 (23.12)

47.79 (20.78)

3 weeks: 37.20 (22.32)

6 weeks: 28.76 (20.93)

3 months: 24.40 (21.85)

6 months: 22.08 (20.88)

3 weeks: 39.67 (23.93)

6 weeks: 36.54 (22.78)

3 months: 30.49 (23.81)

6 months: 28.49 (22.72)

3 weeks: −2.47 (NR)

6 weeks: −7.78 (NR)

3 months: −6.09 (NR)

6 months: −6.41 (NR)

3 weeks: 0.76

6 weeks: 0.90

3 months: 0.90

6 months: 0.51

Ewart et al. (2024)22

1 RCT; George et al. (2018)

7 vs. 5 participants

PT

DASH (12 weeks)

60.14 (NR)

56.86 (NR)

43.89 (NR)

46.68 (NR)

−2.79 (NR)

0.36

Physical performance

Ewart et al. (2024)22

1 RCT; Abd Karim et al. (2023)

32 vs. 32 participants

PRP 2 mL in the lesion, ultrasound-guided; and home exercise program

ROM: Forward Flexion, Abduction, External Rotation, Internal Rotation (6 months)

Forward Flexion: 133.39 (32.56)

126.70 (37.33)

155.18 (30.93)

144.40 (36.29)

10.78 (NR)

0.27

Ewart et al. (2024)22

1 RCT; Abd Karim et al. (2023)

32 vs. 32 participants

PRP 2 mL in the lesion, ultrasound-guided; and home exercise program

ROM: Forward Flexion, Abduction, External Rotation, Internal Rotation (6 months)

Abduction: 146.29 (32.56)

138.00 (34.50)

161.00 (25.84)

156.07 (26.84)

4.93 (NR)

0.58

Ewart et al. (2024)22

1 RCT; Abd Karim et al. (2023)

32 vs. 32 participants

PRP 2 mL in the lesion, ultrasound-guided; and home exercise program

ROM: Forward Flexion, Abduction, External Rotation, Internal Rotation (6 months)

Internal rotation: 57.50 (32.56)

67.03 (27.55)

82.00 (20.92)

86.00 (15.56)

−4 (NR)

0.37

Ewart et al. (2024)22

1 RCT; Abd Karim et al. (2023)

32 vs. 32 participants

PRP 2 mL in the lesion, ultrasound-guided; and home exercise program

ROM: Forward Flexion, Abduction, External Rotation, Internal Rotation (6 months)

External rotation: 54.82 (32.56)

55.67 (29.99)

78.75 (20.53)

73.00 (22.65)

5.75 (NR)

0.43

Ewart et al. (2024)22

1 RCT; Lin et al. (2022)

29 vs. 28 participants

Normal saline (volume NR) in supraspinatus tendon insertion site, ultrasound guided

ROM: Forward Flexion, Abduction, External Rotation, Internal Rotation (12 weeks)

Forward Flexion: 150.5 (14.0)

152.2 (9.0)

156.5 (13.7)

155.3 (9.1)

1.2 (NR)

0.71

Ewart et al. (2024)22

1 RCT; Lin et al. (2022)

29 vs. 28 participants

Normal saline (volume NR) in supraspinatus tendon insertion site, ultrasound guided

ROM: Forward Flexion, Abduction, External Rotation, Internal Rotation (12 weeks)

Abduction: 141.1 (14.0)

140.96 (11.24)

146.6 (14.8)

144.75 (11.03)

1.85 (NR)

0.59

Ewart et al. (2024)22

1 RCT; Lin et al. (2022)

29 vs. 28 participants

Normal saline (volume NR) in supraspinatus tendon insertion site, ultrasound guided

ROM: Forward Flexion, Abduction, External Rotation, Internal Rotation (12 weeks)

Internal rotation: 44.8 (14.0)

45.8 (6.2)

44.6 (6.4)

47.0 (10.3)

−1.2 (NR)

0.64

Ewart et al. (2024)22

1 RCT; Lin et al. (2022)

29 vs. 28 participants

Normal saline (volume NR) in supraspinatus tendon insertion site, ultrasound guided

ROM: Forward Flexion, Abduction, External Rotation, Internal Rotation (12 weeks)

External rotation: 57.6 (14.0)

59.6 (8.8)

56.7 (6.5)

54.5 (9.8)

2.2 (NR)

0.31

Ewart et al. (2024)22

1 RCT; Cole et al. (2017)

17 vs. 19 participants

Corticosteroid injections

(Methylpredni­solone 40 mg [with 0.5% lignocaine]) in subacromial bursa and supraspinatus tendon (hypoechoic or anechoic areas), ultrasound-guided

ROM: Forward Flexion, Abduction, External Rotation (6 weeks, 3, 6 months)

Forward Flexion: 167 (3)

161 (7)

6 weeks: 169 (3)

3 months: 173 (2)

6 months: 172 (2)

6 weeks: 165 (4)

3 months: 172 (3)

6 months: 165 (7)

6 weeks: 4 (NR)

3 months: 1 (NR)

6 months: 7 (NR)

6 weeks: 0.38

3 months: 0.70

6 months: 0.31

Ewart et al. (2024)22

1 RCT; Cole et al. (2017)

17 vs. 19 participants

Corticosteroid injections

(Methylpredni­solone 40 mg [with 0.5% lignocaine]) in subacromial bursa and supraspinatus tendon (hypoechoic or anechoic areas), ultrasound-guided

ROM: Forward Flexion, Abduction, External Rotation (6 weeks, 3, 6 months)

Abduction: 166 (3)

153 (8)

6 weeks: 168 (6)

3 months: 175 (0)

6 months: 175 (2)

6 weeks: 158 (8)

3 months: 163 (7)

6 months: 163 (8)

6 weeks: 10 (NR)

3 months: 12 (NR)

6 months: 12 (NR)

6 weeks: 0.3

3 months: 0.1

6 months: 0.15

Ewart et al. (2024)22

1 RCT; Cole et al. (2017)

17 vs. 19 participants

Corticosteroid injections

(Methylpredni­solone 40 mg [with 0.5% lignocaine]) in subacromial bursa and supraspinatus tendon (hypoechoic or anechoic areas), ultrasound-guided

ROM: Forward Flexion, Abduction, External Rotation (6 weeks, 3, 6 months)

External rotation: 67 (3)

60 (4)

6 weeks: 55 (3)

3 months: 65 (3)

6 months: 61 (3)

6 weeks: 58 (4)

3 months: 57 (5)

6 months: 63 (5)

6 weeks:-3 (NR)

3 months: 8 (NR)

6 months: −2 (NR)

6 weeks: 0.45

3 months: 0.18

6 months: 0.79

Pain intensity or severity

Ewart et al. (2024)22

1 RCT; Lin et al. (2022)

29 vs. 28 participants

Normal saline (volume NR) in supraspinatus tendon insertion site, ultrasound guided

VAS (2, 6, 12 weeks)

5.8 (1.2)

5.7 (1.2)

2 weeks: 3.7 (1.0)

6 weeks: 5.7 (1.0)

12 weeks: 5.6 (1.1)

2 weeks: 5.3 (1.00)

6 weeks: 5.3 (1.3)

12 weeks: 5.0 (1.5)

2 weeks: −1.6 (NR)

6 weeks: 0.4 (NR)

12 weeks: 0.6 (NR)

2 weeks: 0.00

6 weeks: 0.20

12 weeks: 0.0

Ewart et al. (2024)22

1 RCT; Abd Karim et al. (2023)

32 vs. 32 participants

PRP 2 mL in the lesion, ultrasound-guided; and home exercise program

10-point NRS (3, 6 weeks, 3, 6 months)

5.86 (2.41)

6.40 (2.70)

3 weeks: 4.04 (2.40)

6 weeks: 3.39 (2.48)

3 months: 2.82 (2.42)

6 months: 2.71 (2.66)

3 weeks: 4.60 (2.54)

6 weeks: 4.23 (2.45)

3 months: 3.47 (2.57)

6 months: 3.50 (2.78)

3 weeks: −0.56 (NR)

6 weeks: −0.84 (NR)

3 months: −0.65 (NR)

6 months: −0.79 (NR)

3 weeks: 0.55

6 weeks: 0.73

3 months: 0.73

6 months: 0.41

Ewart et al. (2024)22

1 RCT; George et al. (2018)

7 vs. 5 participants

PT

Pain score: 1 to 5, subset of DASH (12 weeks)

3.29 (NR)

3.20 (NR)

1.86 (NR)

2.40 (NR)

−0.54 (NR)

0.25

Ewart et al. (2024)22

1 RCT; Cole et al. (2017)

17 vs. 19 participants

Corticosteroid injections

(Methylpred­nisolone 40 mg [with 0.5% lignocaine]) in subacromial bursa and supraspinatus tendon

Pain severity or intensity: 5-point Likert (activities above the head), (6 weeks, 3, 6 months)a

2.3 (0.2)

2.6 (0.2)

6 weeks: 2.1 (0.2)

3 months: 1.9 (0.2)

6 months: 1.7 (0.2)

6 weeks: 2.4 (0.2)

3 months: 2.2 (0.3)

6 months: 1.7 (0.3)

6 weeks: −0.3 (NR)

3 months: −0.3 (NR)

6 months: 0.0 (NR)

6 weeks: 0.5

3 months: 0.42

6 months: 0.99

ASES = American Shoulder and Elbow Surgeons Standardized Shoulder Assessment; DASH = disability of the arm, shoulder, and hand; MA = meta-analysis; NR = not reported; NRS = numerical rating scale; PRP = platelet-rich plasma; PT = physical therapy; RCT = randomized controlled trial; ROM = range of motion; SPADI = shoulder pain and disability index; SMD = standardized mean difference; SR = systematic review; VAS = visual analogue scale; vs. = versus.

aAdditional results related to this outcome measure are available in the original SR.22

Table 15: Summary of Findings by Outcome and Comparator — Elbow Pain; Dextrose Prolotherapy vs. Placebo

Citation

Evidence source, number of participants (intervention vs. comparator)

Comparator, outcome measure

Baseline, mean (SD)

Follow-up, mean (SD)

Relative effect, mean difference (95% CI)

P value (between groups)

Interven­tion

Comparator

Intervention

Comparator

Pain-related functioning

Ewart et al. (2024)22

1 RCT; Ciftci et al. (2023)

20 vs. 22 participants

Normal saline 1 mL with same injection method

Quick DASH (3, 12 weeks)

55.45 (15.64)

59.99 (14.05)

3 weeks: 28.97 (18.58)

12 weeks: 9.45 (7.35)

3 weeks: 53.74 (13.81)

12 weeks: 39.99 (11.04)

3 weeks: −24.77 (NR)

12 weeks: −30.54 (NR)

3 weeks: 0.003

12 weeks: < 0.001

Ewart et al. (2024)22

1 RCT; Akcay et al. (2020)

30 vs. 30 participants

Normal saline 4.5 mL, with same injection method; and home exercise program

DASH (4, 8, 12 weeks)

Median (range): 65.8 (48.2 to 74.0)

Median (range): 60.0 (46.6 to 74.1)

4 weeks median (range): 48.3 (37.5 to 56.6)

8 weeks Median: 35.0 (14.1 to 46.6)

12 weeks Median: 29.1 (5.0 to 55.0)

4 weeks median (range): 55.8 (40.0 to 68.3)

8 weeks median (range): 44.0 (25.8 to 49.1)

12 weeks median (range): 41.6 (13.0 to 52.5)

4 weeks: −7.5 (NR)

8 weeks: −9 (NR)

12 weeks: −12.5 (NR)

NR

Physical performance

Ewart et al. (2024)22

1 RCT; Ciftci et al. (2023)

20 vs. 22 participants

Normal saline 1 mL with same injection method

Grip strength (3, 12 weeks)

58.50 (40.20)

44.75 (26.38)

3 weeks: 62.25 (39.48)

12 weeks: 71.50 (38.04)

3 weeks: 43.21 (23.53)

12 weeks: 42.50 (20.22)

3 weeks: 19.04 (NR)

12 weeks: 29.0 (NR)

3 weeks: 0.664

12 weeks: 0.126

Ewart et al. (2024)22

1 RCT; Akcay et al. (2020)

30 vs. 30 participants

Normal saline 4.5 mL, with same injection method; and home exercise program

Grip strength (4, 8, 12 weeks)

Median (range): 0.25 (0.15 to 0.36)

Median (range): 0.33 (0.20 to 0.40)

4 weeks median (range): 0.30 (0.25 to 0.40)

8 weeks median (range): 0.40 (0.25 to 0.40)

12 weeks median (range): 0.40 (0.30 to 0.42)

4 weeks median (range): 0.35 (0.25 to 0.45)

8 weeks median (range): 0.38 (0.30 to 0.50)

12 weeks median (range): 0.40 (0.30 to 0.51)

4 weeks: −0.05 (NR)

8 weeks: 0.02 (NR)

12 weeks: 0.0 (NR)

NR

Ewart et al. (2024)22

1 RCT; Scarpone et al. (2008)

12 vs. 12 participants

Normal saline 1.5 mL with same injection method

Grip strength (2, 4 months)

29.8 (18.0)

32.8 (20.6)

8 weeks: 46.4 (23.9)

16 weeks: 54.2 (23.4)

8 weeks: 59.6 (30.2)

16 weeks: 63.1 (29.9)

8 weeks: −13.2 (NR)

16 weeks: −8.9 (NR)

NR

Pain intensity or severity

Ewart et al. (2024)22

1 RCT; Ciftci et al. (2023)

20 vs. 22 participants

Normal saline 1 mL with same injection method

10-point VAS activity (3, 12 weeks)a

6.69 (1.24)

6.18 (0.88)

3 weeks: 3.74 (1.65)

12 weeks: 1.39 (1.10)

3 weeks: 6.92 (1.57)

12 weeks: 6.05 (1.16)

3 weeks: −3.2 (NR)

12 weeks: −4.7 (NR)

3 weeks: 0.38

12 weeks: < 0.001

Ewart et al. (2024)22

1 RCT; Akcay et al. (2020)

30 vs. 30 participants

Normal saline 4.5 mL, with same injection method; and home exercise program

VAS motion (4, 8, 12 weeks)a

median (range): 9.0 (8.0 to 10.0)

median (range): 9.0 (8.0 to 10.0)

4 weeks median (range): 6.0 (4.0 to 9.0)

8 weeks median (range): 4.0 (2.0 to 7.0)

12 weeks median (range): 3.0 (1.0 to 6.0)

4 weeks median (range): 7.0 (5.0 to 8.0)

8 weeks median (range): 5.0 (4.0 to 7.0)

12 weeks median (range): 4.0 (3.0 to 6.0)

4 weeks: −1.0 (NR)

8 weeks: −1.0 (NR)

12 weeks: −1.0 (NR)

4 weeks: 0.16

8 weeks: 0.20

12 weeks: 0.12

Ewart et al. (2024)22

1 RCT; Scarpone et al. (2008)

12 vs. 12 participants

Normal saline 1.5 mL with same injection method

10-point Likert at rest (8, 16 weeks)

5.1 (0.8)

4.5 (1.7)

8 weeks: 3.3 (0.9)

16 weeks: 0.5 (0.4)

8 weeks: 3.6 (1.2)

16 weeks: 3.5 (1.5)

8 weeks: −0.3 (NR)

16 weeks: −3.0 (NR)

8 weeks: NR

16 weeks: ≤ 0.001

DASH = disability of the arm, shoulder, and hand questionnaire; MA = meta-analysis; NR = not reported; Quick DASH = shortened version of DASH (11 items); RCT = randomized controlled trial; ROM = range of motion; SPADI = shoulder pain and disability index; SMD = standardized mean difference; SR = systematic review; VAS = visual analogue scale; vs. = versus.

aAdditional results related to this outcome measure are available in the original SR.22

Table 16: Summary of Findings by Outcome and Comparator — Elbow Pain; Dextrose Prolotherapy vs. Other Comparators

Citation

Evidence source, number of participants (intervention vs. comparator)

Comparator, outcome measure

Baseline, mean (SD)

Follow-up, mean (SD)

Relative effect, mean difference (95% CI)

P value (between groups)

Intervention

Comparator

Intervention

Comparator

Pain-related functioning

Ewart et al. (2024)22

1 RCT; Kaya et al. (2022)

30 vs. 30 participants

3 comparators:

  • Corticosteroid Injection (methylpred­nisolone 20 mg [+ 1.6% prilocaine]) with same injection method

  • ABI 2 mL (+ 0.4% prilocaine) with same method

  • Wrist splint (wear 6 to 8 hour during the day)

PRTEE total (1, 6 months)

73.9 (15.9)

Steroid injectable: 59.2 (19.6)

1 month: 19.1 (18.6)

6 months: 41.6 (26.1)

Steroid injectable:

  • 1 month: 36.2 (21.4)

  • 6 months: 34.1 (35.6)

Steroid injectable: NR

Steroid injectable: NR

Ewart et al. (2024)22

1 RCT; Kaya et al. (2022)

30 vs. 30 participants

3 comparators:

  • Corticosteroid Injection (methylpred­nisolone 20 mg [+ 1.6% prilocaine]) with same injection method

  • ABI 2 mL (+ 0.4% prilocaine) with same method

  • Wrist splint (wear 6 to 8 hour during the day)

PRTEE total (1, 6 months)

73.9 (15.9)

ABI: 67.4 (16.4)

1 month: 19.1 (18.6)

6 months: 41.6 (26.1)

ABI:

  • 1 month: 26.9 (22.9)

  • 6 months: 48.1 (25.1)

ABI

NR

ABI

NR

Ewart et al. (2024)22

1 RCT; Kaya et al. (2022)

30 vs. 30 participants

3 comparators:

  • Corticosteroid Injection (methylpred­nisolone 20 mg [+ 1.6% prilocaine]) with same injection method

  • ABI 2 mL (+ 0.4% prilocaine) with same method

  • Wrist splint (wear 6 to 8 hour during the day)

PRTEE total (1, 6 months)

73.9 (15.9)

Wrist splint: 53.5 (16.2)

1 month: 19.1 (18.6)

6 months: 41.6 (26.1)

Wrist splint:

  • 1 month: 12.4 (15.6)

  • 6 months: 20.1 (19.7)

Wrist splint: NR

Wrist splint: NR

Ewart et al. (2024)22

1 RCT; Bayat et al. (2019)

16 vs. 14 participants

Corticosteroid Injection (methylpredni­solone 40 mg [+ 0.7% lidocaine]) with same injection method; and splint, home exercise program

Quick DASH (1, 3 months)

43.2 (20.8)

52.2 (16.4)

1 month: 24.3 (18.6)

3 months: 14.7 (21.1)

1 month: 34.8 (18.1)

3 months: 34.6 (16.4)

1 month: −10.5 (NR)

3 months: −19.9 (NR)

1 month: 0.14

3 months: 0.01

Ewart et al. (2024)22

1 RCT; Ahadi et al. (2019)

17 vs. 16 participants

ESWT (2,000 J with 1.5 bars intensity, 10 Hz)

Quick DASH (4, 8 weeks)

47.82 (4.78)

41.84 (3.04)

4 weeks: 39.67 (4.30)

8 weeks: 37.39 (4.40)

4 weeks: 22.25 (3.57)

8 weeks: 23.13 (3.20)

4 weeks: 17.42 (NR)

8 weeks: 14.26 (NR)

4 weeks: 0.003

8 weeks: 0.009

Ewart et al. (2024)22

1 RCT; Apaydin et al. (2020)

16 vs. 16 participants

HA 2 mL to most sensitive point of lateral epicondyle

Quick DASH (6, 12 weeks)

53.2 (18.7)

53.1 (12.5)

6 weeks: 20.6 (11.7)

12 weeks: 9.7 (6.4)

6 weeks: 27.9 (11.1)

12 weeks: 24.7 (10.1)

6 weeks: −7.2 (−15.0 to 0.98)

12 weeks: −15 (−21.1 to −8.9)

NR

Ewart et al. (2024)22

1 RCT; Rabago et al. (2013b)

8 vs.10 participants

Waitlist

PRTEE total (4, 8, 16, 32 weeks)a

41.5 (6.4)

50.9 (6.1)

4 weeks: 27.4 (5.3)

8 weeks: 27.2 (5.9)

16 weeks: 22.8 (7.2)

32 weeks: 17.8 (5.55)

4 weeks: 44.8 (5.1)

8 weeks: 46.7 (5.6)

16 weeks: 41.6 (6.9)

32 weeks: NR

4 weeks: −17.4 (NR)

8 weeks: −19.5 (NR)

16 weeks: −14.4 (NR)

32 weeks: NR

4 weeks: ≥ 0.05

8 weeks: ≥ 0.05

16 weeks:− ≥ 0.05

32 weeks: NR

Ewart et al. (2024)22

1 RCT; Yelland et al. (2019)

40 vs. 40 participants

PT (manual therapy and therapeutic exercises), home exercise program

PRTEE total (6, 12, 26, 52 weeks)

31.6 (10.3)

33.5 (10.0)

6 weeks: 24.5 (14.6)

12 weeks: 18.2 (13.5)

26 weeks: 8.9 (8.2)

52 weeks: 4.9 (7.4)

6 weeks: 19.7 (14.3)

12 weeks: 12.2 (12.4)

26 weeks: 9.3 (10.4)

52 weeks: 4.4 (7.4)

6 weeks: 4.8 (NR)

12 weeks: 6 (NR)

26 weeks: 8.9 (NR)

52 weeks: 0.5 (NR)

6 weeks: ≥ 0.05

12 weeks: ≥ 0.05

26 weeks: ≥ 0.05

52 weeks: ≥ 0.05

Physical performance

Ewart et al. (2024)22

1 RCT; Kaya et al. (2022)

30 vs. 30 participants

3 comparators:

  • Corticosteroid Injection (methylpred­nisolone 20 mg [+ 1.6% prilocaine]) with same injection method

  • ABI 2 mL (+ 0.4% prilocaine) with same method

  • Wrist splint (wear 6, 8 hour during the day)

Grip strength (1, 6 months)

22.3 (9.3)

Steroid injectable: 21.9 (10.8)

1 month: −2.0 (4.9)

6 months: −5.95 (5.5)

Steroid injectable:

  • 1 month: −4.17 (4.4)

  • 6 months: −3.96 (5.4)

Steroid injectable: NR

Steroid injectable: NR

Ewart et al. (2024)22

1 RCT; Kaya et al. (2022)

30 vs. 30 participants

3 comparators:

  • Corticosteroid Injection (methylpred­nisolone 20 mg [+ 1.6% prilocaine]) with same injection method

  • ABI 2 mL (+ 0.4% prilocaine) with same method

  • Wrist splint (wear 6, 8 hour during the day)

Grip strength (1, 6 months)

22.3 (9.3)

ABI: 22.98 (7.98)

1 month: −2.0 (4.9)

6 months: −5.95 (5.5)

ABI:

  • 1 month: −3.87 (7.6)

  • 6 months: −7.97 (8.0)

ABI: NR

ABI: NR

Ewart et al. (2024)22

1 RCT; Kaya et al. (2022)

30 vs. 30 participants

3 comparators:

  • Corticosteroid Injection (methylpred­nisolone 20 mg [+ 1.6% prilocaine]) with same injection method

  • ABI 2 mL (+ 0.4% prilocaine) with same method

  • Wrist splint (wear 6, 8 hour during the day)

Grip strength (1, 6 months)

22.3 (9.3)

Wrist splint: 28.3 (13.0)

1 month: −2.0 (4.9)

6 months: −5.95 (5.5)

Wrist splint:

  • 1 month: −2.1 (1.9)

  • 6 months: −2.64 (2.7)

Wrist splint: NR

Wrist splint: NR

Ewart et al. (2024)22

1 RCT; Ahadi et al. (2019)

17 vs. 16 participants

ESWT (2000 J with 1.5 bars intensity, 10 Hz)

Grip strength (4, 8 weeks)

7.02 (0.64)

7.28 (0.52)

4 weeks: 8.02 (0.64)

8 weeks: 8.00 (0.64)

4 weeks: 8.31 (0.49)

8 weeks: 8.36 (0.50)

4 weeks: −0.29 (NR)

8 weeks: −0.36 (NR)

4 weeks: 0.94

8 weeks: 0.77

Ewart et al. (2024)22

1 RCT; Deb et al. (2020)

42 vs. 42 participants

ESWT (2000 J with 1.9 bar intensity, 10 Hz)

Grip strength (1, 3, 6 months)

10.00 (0.99)

9.69 (0.84)

1 month: 11.99 (0.93)

3 months: 13.84 (0.87)

6 months: 15.44 (0.65)

1 month: 10.74 (0.88)

3 months: 11.83 (0.96)

6 months: 13.1 (0.84)

1 month: 1.25 (NR)

3 months: 2.01 (NR)

6 months: 2.34 (NR)

1 month: ≤ 0.001

3 months: ≤ 0.001

6 months: ≤ 0.001

Ewart et al. (2024)22

1 RCT; Apaydin et al. (2020)

16 vs. 16 participants

HA 2 mL to most sensitive point of lateral epicondyle

Grip strength (6, 12 weeks)

19.87 (9.0)

18.13 (8.6)

6 weeks: 24.25 (9.1)

12 weeks: 27.19 (9.6)

6 weeks: 22.06 (8.9)

12 weeks: 22.94 (8.5)

6 weeks: 2.18 (0.06 to 4.53)

12 weeks: 4.25 (2.02 to 7.00)

NR

Ewart et al. (2024)22

1 RCT; Rabago et al. (2013b)

8 vs. 10 participants

Waitlist

Grip strength (4, 8, 16, 32 weeks)

299.4 (61.7)

181.7 (42.6)

4 weeks: NR

8 weeks: 348.6 (56.8)

16 weeks: 364.4 (50.3)

32 weeks: 368.9 (49.9)

4 weeks: NR

8 weeks: 210.1 (40.2)

16 weeks: 200.4 (53.0)

32 weeks: NR

4 weeks: NR

8 weeks: 138.5 (NR)

16 weeks: 164.0 (NR)

32 weeks: NR

4 weeks: NR

8 weeks: P < 0.05

16 weeks: P < 0.05

32 weeks: NR

Pain intensity or severity

Ewart et al. (2024)22

1 RCT; Kaya et al. (2022)

30 vs. 30 participants

3 comparators:

  • Corticosteroid Injection (methyl­prednisolone 20 mg [with 1.6% prilocaine]) with same injection method

  • ABI 2 mL (with 0.4% prilocaine) with same method

  • Wrist splint (wear 6, 8 hour during the day)

VAS (1, 6 months)

73.9 (15.9)

Steroid injectable: 70.0 (15.6)

1 month: 22.4 (23.1)

6 months: 56.0 (34.6)

Steroid injectable:

  • 1 month: 41.2 (31.7)

  • 6 months: 37.9 (39.5)

Steroid injectable: NR

Steroid injectable: NR

Ewart et al. (2024)22

1 RCT; Kaya et al. (2022)

30 vs. 30 participants

3 comparators:

  • Corticosteroid Injection (methyl­prednisolone 20 mg [with 1.6% prilocaine]) with same injection method

  • ABI 2 mL (with 0.4% prilocaine) with same method

  • Wrist splint (wear 6, 8 hour during the day)

VAS (1, 6 months)

73.9 (15.9)

ABI: 76.3 (16.1)

1 month: 22.4 (23.1)

6 months: 56.0 (34.6)

ABI:

  • 1 month: 30.0 (32.3)

  • 6 months: 47.6 (32.1)

ABI: NR

ABI: NR

Ewart et al. (2024)22

1 RCT; Kaya et al. (2022)

30 vs. 30 participants

3 comparators:

  • Corticosteroid Injection (methyl­prednisolone 20 mg [with 1.6% prilocaine]) with same injection method

  • ABI 2 mL (with 0.4% prilocaine) with same method

  • Wrist splint (wear 6, 8 hour during the day)

VAS (1, 6 months)

73.9 (15.9)

Wrist splint: 66.3 (19.1)

1 month: 22.4 (23.1)

6 months: 56.0 (34.6)

Wrist splint:

  • 1 month: 20.0 (20.9)

  • 6 months: 28.1 (28.6)

Wrist splint: NR

Wrist splint: NR

Ewart et al. (2024)22

1 RCT; Gupta et al. (2022)

130 vs. 130 participants

Corticosteroid Injection: (triamcinolone [with 2% lignocaine])

VAS (6, 12, 24, 52 weeks)

68.79 (1.19)

67.16 (2.89)

6 weeks: 52.34 (1.15)

12 weeks: 43.46 (3.18)

24 weeks: 32.70 (2.40)

52 weeks: 21.84 (2.23)

6 weeks: 49.13 (1.63)

12 weeks: 40.68 (2.77)

24 weeks: 32.06 (2.45)

52 weeks: 27.02 (2.23)

6 weeks: 3.2 (NR)

12 weeks: 2.8 (NR)

24 weeks: 0.6 (NR)

52 weeks: −5.18 (NR)

6 weeks: NR

12 weeks: NR

24 weeks: NR

52 weeks: NR

Ewart et al. (2024)22

1 RCT; Bayat et al. (2019)

16 vs. 14 participants

Corticosteroid Injection (methylpredni­solone 40 mg [with 0.7% lidocaine]) with same injection method; and splint, home exercise program

VAS (1, 3 months)

7.3 (1.5)

7.2 (1.8)

1 month: 5.3 (3.1)

3 months: 2.8 (3.2)

1 month: 5.7 (2.6)

3 months: 5.2 (2.4)

1 month: −0.4 (NR)

3 months: −2.4 (NR)

1 month: 0.74

3 months: 0.03

Ewart et al. (2024)22

1 RCT; Ahadi et al. (2019)

17 vs. 16 participants

ESWT (2000 J with 1.5 bars intensity, 10 Hz)

10-point VAS (4, 8 weeks)

7.35 (0.47)

6.13 (0.32)

4 weeks: 5.71 (0.50)

8 weeks: 5.47 (0.53)

4 weeks: 3.19 (0.50)

8 weeks: 2.60 (0.40)

4 weeks: 2.5 (NR)

8 weeks: 2.9 (NR)

4 weeks: 0.01

8 weeks: 0.008

Ewart et al. (2024)22

1 RCT; Deb et al. (2020)

42 vs. 42 participants

ESWT (2000 J with 1.9 bar intensity, 10 Hz)

VAS (1, 3, 6 months)

7.57 (0.67)

7.57 (0.50)

1 month: 5.36 (0.82)

3 months: 3.17 (1.03)

6 months: 1.45 (0.59)

1 month: 6.26 (0.77)

3 months: 4.45 (1.27)

6 months: 3.07 (0.92)

1 month: −0.9 (NR)

3 months: −1.3 (NR)

6 months: −1.6 (NR)

1 month: ≤ 0.001

3 months: ≤ 0.001

6 months: ≤ 0.001

Ewart et al. (2024)22

1 RCT; Apaydin et al. (2020)

16 vs. 16 participants

HA 2 mL to most sensitive point of lateral epicondyle

VAS activity (6, 12 weeks)a

7.00 (1.5)

7.25 (0.8)

6 weeks: 3.75 (1.4)

12 weeks: 2.19 (0.8)

6 weeks: 4.94 (2.4)

12 weeks: 4.06 (2.3)

6 weeks: −1.2

(−1.8 to −0.7)

12 weeks: −1.9

(−2.4 to −1.4)

6 weeks: NR

12 weeks: NR

Ewart et al. (2024)22

1 RCT; Yelland et al. (2019)

40 vs. 40 participants

PT (manual therapy and therapeutic exercises), home exercise program

10-point VAS worst pain in the last week (6, 12, 26, 52 weeks)a

7.4 (1.6)

7.3 (2.0)

6 weeks: 5.4 (2.2)

12 weeks: 4.0 (2.5)

26 weeks: 2.0 (2.0)

52 weeks: 1.1 (2.0)

6 weeks: 3.7 (2.6)

12 weeks: 2.5 (2.6)

26 weeks: 1.6 (2.1)

52 weeks: 0.9 (2.0)

6 weeks: 1.7 (NR)

12 weeks: 1.5 (NR)

26 weeks: 0.4 (NR)

52 weeks: 0.2 (NR)

6 weeks: ≥ 0.05

12 weeks: ≥ 0.05

26 weeks: < 0.05

52 weeks: ≥ 0.05

Health-related quality of life

Ewart et al. (2024)22

1 RCT; Yelland et al. (2019)

40 vs. 40 participants

PT (manual therapy and therapeutic exercises), home exercise program

EuroQoL-5D (6 weeks, 3, 6 months, 1 year)

82.7 (12.9)

80.4 (16.9)

6 weeks: 80.6 (11.8)

12 weeks: 83.1 (9.9)

26 weeks: 86.3 (12.1)

52 weeks: 88.5 (9.3)

6 weeks: 83.9 (13.4)

12 weeks: 83.9 (13.6)

26 weeks: 87.2 (12.7)

52 weeks: 85.3 (9.3)

6 weeks: −3.3 (NR)

12 weeks: −0.8 (NR)

26 weeks: −0.9 (NR)

52 weeks: 3.2 (NR)

6 weeks: ≥ 0.05

12 weeks: NR

26 weeks: ≥ 0.05

52 weeks: ≥ 0.05

ABI = autologous blood injection; DASH = disability of the arm, shoulder, and hand questionnaire; ESWT = extracorporeal shockwave therapy; EuroQol-5D = European Quality of Life-5 dimensions; HA = hyaluronic acid; MA = meta-analysis; NR = not reported; PRTEE = Patient-rated Tennis Elbow Evaluation; PT = physical therapy; Quick DASH = shortened version of DASH (11 items); RCT = randomized controlled trial; ROM = range of motion; SPADI = shoulder pain and disability index; SR = systematic review; VAS = visual analogue scale; vs. = versus.

aAdditional results related to this outcome measure are available in the original SR.22

Table 17: Summary of Findings by Outcome and Comparator — Low Back Pain; Dextrose Prolotherapy vs. Placebo

Citation

Evidence source, number of participants (intervention vs. comparator)

Comparator, outcome measure

Baseline, mean (SD)

Follow-up, mean (SD)

Relative effect, mean difference (95% CI)

P value (between groups)

Intervention

Comparator

Intervention

Comparator

Pain-related functioning

Ewart et al. (2024)22

1 RCT; Dechow et al. (1999)

36 vs. 38 participants

Normal saline 10 mL (with 0.5% lignocaine)

ODI (1, 3, 6 months)

33.99 (NR)

33.06 (NR)

1 month: 35.92 (NR)

3 months: 36.02 (NR)

6 months: 35.22 (NR)

1 month: 33.06 (NR)

3 months: 33.59 (NR)

6 months: 34.56 (NR)

1 month: 2.86 (NR)

3 months: 2.43 (NR)

6 months: 0.66 (NR)

NR

Ewart et al. (2024)22

1 RCT; Klein et al. (1993)

39 vs. 40 participants

Normal saline 30 mL

RMDQ (6 months)

9.36 (3.6)

8.25 (3.3)

4.04 (3.71)

4.38 (4.05)

−0.34 (NR)

0.068

Ewart et al. (2024)22

1 RCT; Ongley et al. (1987)

40 vs. 41 participants

Normal saline 20 mL; home exercise program

Modified RMDQ/WDI (1, 3, 6 months)

11.45 (NR)

11.82 (NR)

1 month: 4.00 (NR)

3 months: 4.70 (NR)

6 months: 3.43 (NR)

1 month: 8.37 (NR)

3 months: 8.49 (NR)

6 months: 8.29 (NR)

1 month: −4.37 (NR)

3 months: −3.79 (NR)

6 months: −4.86 (NR)

1 month: < 0.001

3 months: < 0.004

6 months: < 0.001

Ewart et al. (2024)22

1 RCT; Yelland et al. (2004)

54 vs. 56 participants

Normal saline 10 mL; 50%

Modified RMDQ (12, 24 months)

13.7 (5.0)

14.3 (4.5)

12 months: 8.0 (NR)

24 months: 8.6 (NR)

12 months: 9.8 (NR)

24 months: 9.4 (NR)

12 months: −1.8 (NR)

24 months: −0.8 (NR)

NR

Physical performance

Ewart et al. (2024)22

1 RCT; Dechow et al. (1999)

36 vs. 38 participants

Normal saline 10  mL (with 0.5% lignocaine)

ROM: Lumbar Flexion (1, 3, 6 months)

4.83 (NR)

5.28 (NR)

1 month: 5.52 (4.86)

3 months: 5.45 (5.1)

6 months: 5.4 (4.8)

1 month: 5.49 (NR)

3 months: 5.23 (NR)

6 months: 5.77 (NR)

1 month: 0.03 (NR)

3 months: 0.22 (NR)

6 months: −0.37 (NR)

NR

Ewart et al. (2024)22

1 RCT; Klein et al. (1993)

39 vs. 40 participants

Normal saline 30 mL (with 0.3% lignocaine); home exercise program

B-200 Triaxial Dynamometer ROM: Rotation, Flexion-Extension, Side Flexion (6 months)

81.9 (11.8)

84.0 (9.9)

Rotation: 91.8 (8.6)

Flexion-Extension: 100.5 (11.1)

Side Flexion: 78.2 (11.4)

Rotation: 93.8 (6.2)

Flexion-Extension: 102.3 (11.7)

Side Flexion: 78.1 (11.7)

Rotation: −2 (NR)

Flexion-Extension: −1.80 (NR)

Side Flexion: 0.10 (NR)

NR

Pain intensity or severity

Ewart et al. (2024)22

1 RCT; Dechow et al. (1999)

36 vs. 38 participants

Normal saline 10 mL (with 0.5% lignocaine)

VAS (1, 3, 6 months)

5.39 (NR)

5.31 (NR)

1 month: 5.2 (NR)

3 months: 5.1 (NR)

6 months: 5.19 (NR)

1 month: 4.77 (NR)

3 months: 5.28 (NR)

6 months: 4.47 (NR)

1 month: 0.43 (NR)

3 months: −0.18 (NR)

6 months: 0.72 (NR)

NR

Ewart et al. (2024)22

1 RCT; Klein et al. (1993)

39 vs. 40 participants

Normal saline 30 mL

VAS (6 months)

4.88 (1.3)

4.56 (1.12)

2.85 (1.88)

2.29 (1.67)

0.56 (NR)

0.056

Ewart et al. (2024)22

1 RCT; Ongley et al. (1987)

40 vs. 41 participants

Normal saline 20 mL; home exercise program

VAS (1, 3, 6 months)

3.78 (NR)

3.99 (0.19)

1 month: 2.13 (NR)

3 months: 1.77 (NR)

6 months: 1.50 (NR)

1 month: 3.06 (0.29)

3 months: 2.93 (0.25)

6 months: 3.08 (0.28)

1 month: −0.93 (NR)

3 months: −1.16 (NR)

6 months: −1.58 (NR)

1 month: < 0.01

3 months: < 0.001

6 months: < 0.001

Ewart et al. (2024)22

1 RCT; Yelland et al. (2004)

54 vs. 56 participants

Normal saline 10 mL; 50%

VAS (12, 24 months)

51.9 (19.3)

55.0 (20.7)

12 months: 33.21 (NR)

24 months: 32.83 (NR)

12 months: 36.79 (NR)

24 months: 37.17 (NR)

12 months: −3.58 (NR)

24 months: −4.34 (NR)

12 months: NR

24 months: NR

DPQ = Dallas Pain Questionnaire; MA = meta-analysis; NR = not reported; ODI = Oswestry Disability Index; RCT = randomized controlled trial; RMDQ = Roland Morris Disability Questionnaire; ROM = range of motion; SR = systematic review; VAS = visual analogue scale; vs. = versus; WDI = Waddell Disability Index.

Table 18: Summary of Findings by Outcome and Comparator — Low Back Pain; Dextrose Prolotherapy vs. Other Comparators

Citation

Evidence source, number of participants (intervention vs. comparator)

Comparator, outcome measure

Baseline, mean (SD)

Follow-up, mean (SD)

Relative effect, mean difference (95% CI)

P value (between groups)

Intervention

Comparator

Intervention

Comparator

Pain-related functioning

Ewart et al. (2024)22

1 observational cohort; Yildirim et al. (2021)

87 vs. 91 participants

Corticosteroid injections

(20 mg methylpredni­solone [with 0.25% bupivacaine]), injection at single-level facet joint

ODI (3 months)

55.93 (10.74)

56.59 (10.47)

39.13 (8.11)

32.85 (7.50)

6.28 (NR)

0.000

Ewart et al. (2024)22

1 RCT; Kim et al. (2010)

24 vs. 26 participants

Corticosteroid injections (Intra-articular triamcinolone 40 mg [with 0.1% levobupivacaine]), fluoroscopy guided at sacroiliac joint

ODI (2 weeks)

33.9 (15.5)

35.7 (20.4)

11.1 (10.0)

15.5 (10.7)

- 4.40 (NR)

NR

Ewart et al. (2024)22

1 RCT; Raissi et al. (2022)

20 vs. 20 participants

Corticosteroid injections (2.5 mL triamcinolone), ultrasound-guided at sacroiliac joint

DPQ (2, 8 weeks)

217.89 (72.87)

208.56 (70.69)

2 weeks: 182.94 (84.62)

8 weeks: 195.83 (47.41)

2 weeks: 165.54 (62.12)

8 weeks: 158.83 (78.81)

2 weeks: 17.40 (NR)

8 weeks: 37.00 (NR)

NR

Pain intensity or severity

Ewart et al. (2024)22

1 observational cohort; Yildirim et al. (2021)

87 vs. 91 participants

Corticosteroid injections (20 mg methylpredni­solone [with 0.25% bupivacaine]), injection at single-level facet joint

VAS (1, 15 days, 3 months)

7.57 (0.98)

8.45 (0.69)

1 day: 3.48 (1.06)

15 days: 2.80 (0.85)

3 months: 3.11 (1.02)

1 day: 1.67 (0.88)

15 days: 3.02 (1.45)

3 months: 5.38 (1.99)

1 day: 1.81 (NR)

15 days: −0.22 (NR)

3 months: −2.27 (NR)

1 day: 0.000

15 days: 0.225

3 months: 0.000

Ewart et al. (2024)22

1 RCT; Kim et al. (2010)

24 vs. 26 participants

Corticosteroid injections (Intra-articular triamcinolone 40 mg [with 0.1% levobupivacaine]), fluoroscopy guided at sacroiliac joint

VAS (2 weeks)

6.3 (NR)

6.7 (NR)

1.4 (1.1)

1.9 (0.9)

−0.50 (NR)

NR

Ewart et al. (2024)22

1 RCT; Raissi et al. (2022)

20 vs. 20 participants

Corticosteroid injections (2.5 mL triamcinolone), ultrasound-guided at sacroiliac joint

VAS (2, 8 weeks, 9 months)

8.17 (1.54)

7.76 (1.70)

2 weeks: 4.50 (2.12)

8 weeks: 4.11 (1.45)

9 months: 2.67 (1.24)

2 weeks: 3.71 (2.12)

8 weeks: 4.48 (2.60)

9 months: 2.62 (1.63)

2 weeks: 0.79 (NR)

8 weeks: −0.37 (NR)

9 months: 0.05 (NR)

2 weeks: NR

8 weeks: NR

9 months: NR

DPQ = Dallas Pain Questionnaire; MA = meta-analysis; NR = not reported; ODI = Oswestry Disability Index; RCT = randomized controlled trial; RMDQ = Roland Morris Disability Questionnaire; ROM = range of motion; SR = systematic review; VAS = visual analogue scale; vs. = versus.

Table 19: Summary of Findings by Outcome and Comparator — TMJ; Dextrose Prolotherapy vs. Placebo

Citation

Evidence source, number of participants (intervention vs. comparator)

Comparator, outcome measure

Baseline, mean (SD)

Follow-up, mean (SD)

Relative effect, mean difference (95% CI)

P value (between groups)

Intervention

Comparator

Intervention

Comparator

Pain-related functioning

Saramantos et al. (2025)25

SR with MA (3 RCTs)

46 vs. 43 participants

Placebo

Subluxation / jaw mobility (time frame NS)

NR

NR

NR

NR

−1.18 (−2.15 to −0.20)

0.02

Physical performance

Saramantos et al. (2025)25

SR with MA (6 RCTs)

86 vs. 81 participants

Placebo

MIO (3 or 5 months)

NR

NR

NR

NR

0.84 (−2.12 to 3.80)

0.58

Zhou et al. (2025)27

SR with MA (3 RCTs)

48 vs. 27 participants

Placebo

MMO score (1, 3, or 11.8 months)

NR

NR

NR

NR

−3.63 (−6.76 to −0.49)

0.02

Ewart et al. (2024)22

1 RCT; Haggag et al. (2022)

15 vs. 15 participants

Normal saline 2 mL (with 4% articaine) with same injection method

MMO (1, 3, 6 months)

27.5 (NR)

25.7 (NR)

1 month: 40.8 (NR)

3 months: 41.3 (NR)

6 months: 41.7 (NR)

1 month: 35.3 (NR)

3 months: 29.7 (NR)

6 months: 29.1 (NR)

1 month: 5.5 (NR)

3 months: 11.6 (NR)

6 months: 12.6 (NR)

1 month: 0.041

3 months: < 0.001

6 months: < 0.001

Pain intensity or severity

Saramantos et al. (2025)25

SR with MA (5 RCTs)

80 vs. 75 participants

Placebo

VAS for pain (3 or 5 months)

NR

NR

NR

NR

−1.10 (−1.58 to −0.62)

< 0.00001

Zhou et al. (2025)27

SR with MA (2 RCTs)

42 vs. 21 participants

Placebo

VAS for pain (1 month or 11.8 months)

NR

NR

NR

NR

−0.95 (−1.75 to −0.15)

0.02

Ewart et al. (2024)22

1 RCT; Haggag et al. (2022)

15 vs. 15 participants

Normal saline 2 mL (with 4% articaine) with same injection method

NRS (1, 3, 6 months)

8.1

7.3

1 month: 2.3

3 months: 2.3

6 months: 2.1

1 month: 3.7

3 months: 5.6

6 months: 6.3

1 month: −1.4 (NR)

3 months: −3.3 (NR)

6 months: −4.2 (NR)

1 month: 0.015

3 months: < 0.001

6 months: < 0.001

CI = confidence interval; MA = meta-analysis; MIO = maximal mal incisor opening; MMO = maximal mouth opening; NR = not reported; NRS = numerical rating scale; NS = not specified; RCT = randomized controlled trial; SD = standard deviation; SMD = standardized mean difference; SR = systematic review; TMJ = temporomandibular joint; VAS = visual analogue scale; vs. = versus.

Table 20: Summary of Findings by Outcome and Comparator — TMJ; Dextrose Prolotherapy vs. Other Comparators

Citation

Evidence source, number of participants (intervention vs. comparator)

Comparator, outcome measure

Baseline, mean (SD)

Follow-up, mean (SD)

Relative effect, mean difference (95% CI)

P value (between groups)

Intervention

Comparator

Intervention

Comparator

Pain-related functioning

Saramantos et al. (2025)25

SR with MA (2 RCTs)

42 vs. 42 participants

ABI

VAS for pain (time frame NS)

NR

NR

NR

NR

−0.49

(−0.87 to −0.11)

0.01

Ewart et al. (2024)22

1 observational Cohort; Elwerfelli et al. (2019)

7 vs. 7 participants

Arthrocentesis and lavage with 50 mL normal

VAS (6 weeks)

NR

NR

NR

NR

NR

NR

Ewart et al. (2024)22

1 RCT; Hassanien et al. (2020)

10 vs. 10 participants

Low-level laser therapy (980 nm wavelength, 0.2 Watt)

VAS (2, 4 weeks)

5.88 (2.36)

4.38 (1.51)

2 weeks: 3.75 (1.58)

4 weeks: 2.13 (0.99)

2 weeks: 4.38 (2.07)

4 weeks: 3.50 (2.27)

2 weeks: −0.6 (NR)

4 weeks: −1.4 (NR)

2 weeks: NR

4 weeks: 0.138

Ewart et al. (2024)22

1 RCT; Mahmoud et al. (2018)

15 vs. 15 participants

2 comparators:

  • Arthrocen­tesis with HA intra-articular (volume and location NR)

  • PRP 1 mL intra-articular (location NR)

VAS (1, 3, 6, 12 months)

9.9 (NR)

Arthrocen­tesis with HA: 9.9 (NR)

1 month: 4.2 (NR)

3 months: 3.3 (NR)

6 months: 3.7 (NR)

12 months: 3.7 (NR)

Arthrocentesis with HA:

  • 1 month: 4.3 (NR)

  • 3 months: 3.6 (NR)

  • 6 months: 3.7 (NR)

  • 12 months: 3.7 (NR)

Arthrocentesis with HA:

  • 1 month: −0.1 (NR)

  • 3 months: −0.3 (NR)

  • 6 months: 0 (NR)

  • 12 months: 0 (NR)

Arthrocen­tesis with HA:

  • 1 month: > 0.05

  • 3 months: > 0.05

  • 6 months: > 0.05

  • 12 months: > 0.05

Ewart et al. (2024)22

1 RCT; Mahmoud et al. (2018)

15 vs. 15 participants

2 comparators:

  • Arthrocen­tesis with HA intra-articular (volume and location NR)

  • PRP 1 mL intra-articular (location NR)

VAS (1, 3, 6, 12 months)

9.9 (NR)

PRP: 10.0 (NR)

1 month: 4.2 (NR)

3 months: 3.3 (NR)

6 months: 3.7 (NR)

12 months: 3.7 (NR)

PRP:

  • 1 month: 5.3 (NR)

  • 3 months: 3.1 (NR)

  • 6 months: 1.6 (NR)

  • 12 months: 1.1 (NR)

PRP:

  • 1 month: −1.1 (NR)

  • 3 months: 0.2 (NR)

  • 6 months: 2.1 (NR)

  • 12 months: 2.6 (NR)

PRP:

  • 1 month: > 0.05

  • 3 months: > 0.05

  • 6 months: < 0.05

  • 12 months: < 0.05

Ewart et al. (2024)22

1 RCT; Priyadarshini et al. (2021)

17 vs. 17 participants

Occlusal splints

NRS - Pain (1, 3, 6, 12 months)

5.76 (1.95)

5.35 (1.935)

1 month: 0.59 (0.51)

3 months: 0.59 (0.51)

6 months: 0.47 (0.51)

12 months: 0.47 (0.51)

1 month: 3.47 (2.04)

3 months: 3.41 (1.94)

6 months: 3.41 (1.87)

12 months: 3.29 (0.51)

1 month: −2.9 (NR)

3 months: −2.8 (NR)

6 months: −2.9 (NR)

12 months: −2.8 (NR)

1 month: ≤ 0.001

3 months: ≤ 0.001

6 months: ≤ 0.001

12 months: ≤ 0.001

Physical performance

Zhou et al. (2025)27

SR with MA (3 RCTs)

61 vs. 61 participants

ABI

MMO score (6 months)

NR

NR

NR

NR

−0.42 (−4.07 to 3.22)

0.82

Ewart et al. (2024)22

SR with MA (3 RCTs)

55 vs. 50 participants

ABI

MMO score (6 months)

NR

NR

NR

NR

SMD = 0.71

(−1.34 to 2.76)

NR

Ewart et al. (2024)22

1 observational Cohort; Elwerfelli et al. (2019)

7 vs. 7 participants

Arthrocen­tesis and lavage with 50 mL normal

MMO (1 day, 1, 2, 3, 4, 5, 6 weeks)

23.14 (3.53)

24.43 (2.82)

1 day: 34.43 (1.62)

1 week: 40.29 (1.98)

2 weeks: 41.86 (2.67)

3 weeks: 44.71 (1.25)

4 weeks: 45.29 (1.25)

5 weeks: 45.29 (1.25)

6 weeks: 45.29 (1.25)

1 day: 34.14 (2.54)

1 week: 39.57 (2.57)

2 weeks: 39.43 (2.70)

3 weeks: 41.0 (1.25)

4 weeks: 41.43 (3.26)

5 weeks: 41.57 (3.05)

6 weeks: 41.57 (3.05)

1 day: 0.3 (NR)

1 week: 0.7 (NR)

2 weeks: 2.4 (NR)

3 weeks: 3.7 (NR)

4 weeks: 3.9 (NR)

5 weeks: 3.7 (NR)

6 weeks: 3.7 (NR)

1 day: 0.806

1 week: 0.571

2 weeks: 0.117

3 weeks: 0.035

4 weeks: 0.020

5 weeks: 0.018

6 weeks: 0.018

Ewart et al. (2024)22

1 RCT; Hassanien et al. (2020)

10 vs. 10 participants

Low-level laser therapy (980 nm wavelength, 0.2 Watt)

MMO (2, 4 weeks)

35.213 (3.776)

32.750 (0.463)

2 weeks: 39.488 (2.713)

4 weeks: 43.375 (1.707)

2 weeks: 35.250 (1.282)

4 weeks: 37.375 (1.923)

2 weeks: 4.2 (NR)

4 weeks: 6.0 (NR)

2 weeks: 0.001

4 weeks: ≤ 0.001

Ewart et al. (2024)22

1 RCT; Mahmoud et al. (2018)

15 vs. 15 participants

2 comparators:

  • Arthrocen­tesis with HA intra-articular (volume and location NR)

  • PRP 1 mL intra-articular (location NR)

MMO (1, 3, 6, 12 months)

36.7 (NR)

Arthrocen­tesis with HA: 34.6 (NR)

1 month: 40.5 (NR)

3 months: 41.5 (NR)

6 months: 39.8 (NR)

12 months: 39.1 (NR)

Arthrocentesis with HA:

  • 1 month: 39.7 (NR)

  • 3 months: 39.8 (NR)

  • 6 months: 38.9 (NR)

  • 12 months: 38.7 (NR)

Arthrocentesis with HA:

  • 1 month: 0.8 (NR)

  • 3 months: 1.7 (NR)

  • 6 months: 0.9 (NR)

  • 12 months: 0.4 (NR)

Arthrocen­tesis with HA:

  • 1 month: > 0.05

  • 3 months: > 0.05

  • 6 months: > 0.05

  • 12 months: > 0.05

Ewart et al. (2024)22

1 RCT; Mahmoud et al. (2018)

15 vs. 15 participants

2 comparators:

  • Arthrocen­tesis with HA intra-articular (volume and location NR)

  • PRP 1 mL intra-articular (location NR)

MMO (1, 3, 6, 12 months)

36.7 (NR)

PRP: 41.3 (NR)

1 month: 40.5 (NR)

3 months: 41.5 (NR)

6 months: 39.8 (NR)

12 months: 39.1 (NR)

PRP:

  • 1 month: 38.0 (NR)

  • 3 months: 35.9 (NR)

  • 6 months: 33.8 (NR)

  • 12 months: 33.7 (NR)

PRP:

  • 1 month: 2.5 (NR)

  • 3 months: 5.6 (NR)

  • 6 months: 6.0 (NR)

  • 12 months: 5.4 (NR)

PRP:

  • 1 month: > 0.05

  • 3 months: < 0.05

  • 6 months: < 0.05

  • 12 months: < 0.05

Ewart et al. (2024)22

1 RCT; Priyadarshini et al. (2021)

17 vs. 17 participants

Occlusal splints

MMO (1, 3, 6, 12 months)

36.06 (11.003)

33.88 (9.130)

1 month: 40.65 (8.246)

3 months: 41.18 (8.017)

6 months: 41.35 (7.960)

12 months: 41.29 (7.967)

1 month: 34.71 (8.402)

3 months: 34.65 (8.389)

6 months: 34.82 (8.346)

12 months: 35.06 (7.967)

1 month: 5.9 (NR)

3 months: 6.5 (NR)

6 months: 6.5 (NR)

12 months: 6.2 (NR)

1 month: 0.046

3 months: 0.027

6 months: 0.026

12 months: 0.032

ABI = autologous blood injection; CI = confidence interval; HA = hyaluronic acid; MA = meta-analysis; MIO = maximal mal incisor opening; MMO = maximal mouth opening; NR = not reported; NRS = numerical rating scale; NS = not specified; PRP = Platelet-Rich Plasma; RCT = randomized controlled trial; SD = standard deviation; SMD = standardized mean difference; SR = systematic review; TMJ = temporomandibular joint; VAS = visual analogue scale; vs. = versus.

Table 21: Summary of Findings by Pain Conditions and Comparator — Other Pain Conditions

Citation

Evidence source, number of participants (intervention vs. comparator)

Comparator, outcome measure

Baseline, mean (SD)

Follow-up, mean (SD)

Relative effect, mean difference (95% CI)

P value (between groups)

Intervention

Comparator

Intervention

Comparator

Non-arthritis knee pain

Ewart et al. (2024)22

1 RCT; Babaei-Ghazani et al. (2023)

25 vs. 25 participants

2 comparators:

  • Cortico­steroid injections (Triamci­nolone 40 mg), ultrasound guided

  • Oxygen-Ozone injection 5 mL, ultrasound-guided

Pes anserine bursitis; WOMAC (1, 8 weeks)a

59.3 (16.8)

Cortico­steroid: 63.2 (13.3)

1 week: 56.7 (21.5)

8 weeks: 38.1 (15.5)

Corticosteroid:

  • 1 week: 44.1 (21.0)

  • 8 weeks: 48.0 (19.2)

Corticosteroid:

  • 1 week: 12.6 (NR)

  • 8 weeks: −9.9 (NR)

Cortico­steroid: NR

Ewart et al. (2024)22

1 RCT; Babaei-Ghazani et al. (2023)

25 vs. 25 participants

2 comparators:

  • Cortico­steroid injections (Triamci­nolone 40 mg), ultrasound guided

  • Oxygen-Ozone injection 5 mL, ultrasound-guided

Pes anserine bursitis; WOMAC (1, 8 weeks)a

59.3 (16.8)

Oxygen-ozone: 58.6 (11.2)

1 week: 56.7 (21.5)

8 weeks: 38.1 (15.5)

Oxygen-ozone:

  • 1 week: 43.2 (16.8)

  • 8 weeks: 33.0 (15.3)

Oxygen-ozone:

  • 1 week: 13.5 (NR)

  • 8 weeks: 5.1 (NR)

Oxygen-ozone: NR

Ewart et al. (2024)22

1 RCT; Wu et al. (2022)

35 vs. 35 participants

Normal saline 4 mL (with 0.5% lidocaine), ultrasound-guided

Osgood-Schlatter disease; VISA-P (3 weeks, 6, 12 months)

49.1 (5.9)

49.4 (5.7)

3 weeks: 76.2 (1.1)

6 months: 80.8 (1.1)

12 months: 83.1 (1.3)

3 weeks: 50.8 (1.1)

6 months: 74.6 (1.1)

12 months: 77.6 (1.3)

3 weeks: 25.4 (NR)

6 months: 6.2 (NR)

12 months: 5.5 (NR)

3 weeks: < 0.0001

6 months: < 0.0001

12 months: 0.0026

Ewart et al. (2024)22

1 observational study; Cho et al. (2017)

10 vs. 10 participants

Supervised exercise program only

Chronic patellar tendinopathy;

VISA-P (6, 12 weeks)a

52.4 (9.7)

59.9 (13.8)

6 weeks: 57.2 (12.8)

12 weeks: 62.6 (11.1)

6 weeks: 73.7 (11.9) 12 weeks: 78.1 (10.6)

6 weeks: −6.1 (NR)

12 weeks: 0.9 (NR)

NR

Other types of foot pain (not plantar fasciitis)

Ewart et al. (2024)22

1 observational study; Akpancar et al. (2019)

27 vs. 27 participants

2 mL PRP intra-articular and 2 mL PRP at tibial edge and talar dome adjacent to the joint

Osteochondral lesions of the talus; AOS (21 days, 3, 6, 12 months)a

129.4 (20.0)

137.4 (20.9)

21 days: 75.2 (23.3)

3 months: 51.4 (28.3)

6 months: 36.9 (25.8)

12 months: 29.9 (25.9)

21 days: 86.5 (28.0)

3 months: 49.9 (20.5)

6 months: 33.3 (15.6)

12 months: 30.1 (19.5)

21 days: −11.3 (NR)

3 months: 1.5 (NR)

6 months: 3.6 (NR)

12 months: −0.2 (NR)

21 days: 0.13

3 months: 0.84

6 months: 0.57

12 months: 0.98

Ewart et al. (2024)22

1 RCT; Hadianfard et al. (2023)

16 vs. 16 participants

Cortico­steroid injections

(Methylpredni­solone acetate 40 mg [with 1% lidocaine])

Hallux rigidus; MOXFQ (1, 4, 8 weeks)a

45.5 (NR)

49.6 (NR)

1 week: 29.1 (NR)

4 weeks: 33.1 (NR)

8 weeks: 33.1 (NR)

1 week: 28.6 (NR)

4 weeks: 33.1 (NR)

8 weeks: 33.8 (NR)

1 week: −0.5 (NR)

4 weeks: 0.0 (NR)

8 weeks: −0.7 (NR)

1 week: 0.93

4 weeks: 1.0

8 weeks: 0.82

Ewart et al. (2024)22

1 RCT; Yelland et al. (2011)

14 vs. 15 participants

Eccentric loading exercises only

Achilles tendinosis; VISA-A (6 weeks, 3, 6, 12 months)

50.3 (NR)

57.6 (NR)

6 weeks: 74.5 (NR)

3 months: 76.4 (NR)

6 months: 81.6 (NR)

12 months: 91.5 (NR)

6 weeks: 70.3 (NR)

3 months: 79.7 (NR)

6 months: 76.3 (NR)

12 months: 81.5 (NR)

6 weeks: 4.2 (NR)

3 months: −3.3 (NR)

6 months: 5.3 (NR)

12 months: 10.0 (NR)

6 weeks: 0.005

3 months: NR

6 months: NR

12 months: 0.007

Hand pain conditions

Ewart et al. (2024)22

1 RCT; Hooper et al. (2011)

20 vs. 19 participants

1% lidocaine 5 mL using same injection technique

Midcarpal or scapholunate ligament laxity;

PRWE (3, 12 months)

Physical performance: Grip strength, flexion, extension, supination, pronation (12 months)

PRWE

43.4 (11.9)

42.2 (14.9)

NR

NR

NR

3 months: 0.48

12 months: 0.04

Ewart et al. (2024)22

1 RCT; Hooper et al. (2011)

20 vs. 19 participants

1% lidocaine 5 mL using same injection technique

Midcarpal or scapholunate ligament laxity;

PRWE (3, 12 months)

Physical performance: Grip strength, flexion, extension, supination, pronation (12 months)

Physical performance

NR

NR

NR

NR

NR

Grip strength: 0.40

Flexion: 0.50

Extension: 0.59

Supination: 0.53

Pronation: 0.90

Ulnar deviation: 0.65

Radial deviation: 0.22

Ewart et al. (2024)22

1 RCT; Jahangiri et al. (2014)

30 vs. 30 participants

Corticosteroid injections

(40 mg methylpredni­solone acetate [with 2% lidocaine]) in the snuffbox and intra- and peri-articular locations

Osteoarthritis of first carpometa­carpal (CMC) joint; HAQDI (1, 2, 6 months)

Lateral Pinch Strength (1, 2, 6 months)a

HAQDI

4.6 (1.8)

4.37 (1.4)

NR

NR

1 month: −0.5 (NR)

2 months: −1.0 (NR)

6 months: −1.0 (NR)

1 month: 0.15

2 months: 0.01

6 months: 0.01

Ewart et al. (2024)22

1 RCT; Jahangiri et al. (2014)

30 vs. 30 participants

Corticosteroid injections

(40 mg methylpredni­solone acetate [with 2% lidocaine]) in the snuffbox and intra- and peri-articular locations

Osteoarthritis of first carpometa­carpal (CMC) joint; HAQDI (1, 2, 6 months)

Lateral Pinch Strength (1, 2, 6 months)a

Lateral pinch strength

9.6 (3.4)

11.6 (3.6)

NR

NR

1 month: −2.9 (NR)

2 months: −1.1 (NR)

6 months: −0.8 (NR)

1 month: 0.005

2 months: 0.25

6 months: 0.45

Ewart et al. (2024)22

1 RCT; Ustun et al. (2023)

23 vs. 23 participants

Paraffin wax

Bilateral hand osteoarthritis; DHI (2 weeks, 1, 3 months)a

16.76 (10.73)

8.90 (5.38)

2 weeks: 9.43 (7.49)

1 month: 5.86 (4.22)

3 months: 5.57 (3.57)

2 weeks: 4.52 (4.23)

1 month: 4.00 (3.38)

3 months: 3.90 (3.69)

2 weeks: 4.91 (NR)

1 month: 1.86 (NR)

3 months: 1.67 (NR)

2 weeks: 0.004

1 month: 0.20

3 months: 0.064

Other conditions

Ewart et al. (2024)22

1 observational study; Abd et al. (2019)

60 vs. 60 participants

Repetitive transcranial magnetic stimulation (rTMS) 10 Hz

Fibromyalgia; FIQR (1, 2 months)a

61.95 (9.75)

65.00 (8.64)

1 month: 48.42 (8.87)

2 months: 31.23 (10.67)

1 month: 52.43 (11.27)

2 months: 51.71 (12.57)

1 month: −4.01 (NR)

2 months: −20.48 (NR)

1 month: 0.294

2 months: < 0.001

Ewart et al. (2024)22

1 RCT; Gul et al. (2020)

20 vs. 21 participants

PT or home exercise program

Hip osteo­arthritis due to develop­mental dysplasia; VAS (21 days, 3 months, 6 months, 12 months)

7.83 (1.19)

7.43 (1.12)

21 days: 4.65 (1.40)

3 months: 3.82 (2.05)

6 months: 3.17 (2.44)

12 months: 3.26 (2.32)

21 days: 5.52 (1.08)

3 months: 3.82 (2.05)

6 months: 4.56 (2.33)

12 months: 3.26 (2.32)

21 days: −0.87 (NR)

3 months: −1.00 (NR)

6 months: −1.39 (NR)

12 months: −1.26 (NR)

21 days: 0.024

3 months: 0.045

6 months: 0.027

12 months: 0.011

Ewart et al. (2024)22

1 observational study; Senturk et al. (2017)

21 vs. 13 participants

5 mg/kg naproxen sodium twice daily

Tietze syndrome; VAS (1 day, 1 week, 4 weeks)

7.1 (1.2)

7.2 (1.2)

1 day: 2.2 (0.9)

1 week: 2.1 (1.0)

4 weeks: 1.5 (0.7)

1 day: 2.6 (1.0)

1 week: 2.1 (1.0)

4 weeks: 2.6 (0.8)

1 day: −0.40 (NR)

1 week: −0.70 (NR)

4 weeks: −1.10 (NR)

1 day: NR

1 week: NR

4 weeks: 0.001

AOS = Ankle Osteoarthritis Scale; CI = confidence interval; DHI = Duruoz Hand Index; FIQR = Revised Fibromyalgia Impaction Questionnaire; KL = Kellgren-Lawrence; HAQDI = Health Assessment Questionnaire Disability Index; MOXFQ = Manchester-Oxford foot questionnaire; NR = not reported; OKS = Oxford Knee Score; PRP = platelet-rich plasma; PRWE = Patient Rated Wrist Evaluation; PT = physical therapy; RCT = randomized controlled trials; SD = standard deviation; SMD = standardized mean difference; SR = systematic review; VAS = visual analogue scale; VISA-A = Victorian Institute of Sport Assessment-Achilles; VISA-P = Victorian Institute of Sport Assessment-Patella; vs. = versus; WOMAC = Western Ontario and McMaster Universities Arthritis Index.

aAdditional results related to this study are available in the original SR.22

Appendix 6: Overlap Between Included Systematic Reviews

Please note that this appendix has not been copy-edited.

Table 22: Overlap in Relevant Primary Studies Between Included Systematic Reviews

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Thamrongskulsiri et al. (2025)26

Zhou et al. (2025)27

Ewart et al. (2024)22

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No

No

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No

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No

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No

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No

No

No

No

Yes

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No

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No

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No

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No

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No

No

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No

No

No

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No

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Yes

No

No

Yes