The report is a product of the VA/HSR Evidence Synthesis Program.

Dextrose Prolotherapy for Musculoskeletal Pain: A Systematic Review

Takeaway: Dextrose prolotherapy — injections of dextrose solutions into (intra-articular) or around (extra-articular) an affected structure — appeared to have varying effects on pain-related functioning and physical performance for different musculoskeletal pain conditions. Intra-articular dextrose prolotherapy probably had little to no benefit for pain-related functioning or physical performance in knee osteoarthritis, compared with normal saline injections. For shoulder pain due to mixed bursitis and rotator cuff pathology, extra-articular dextrose prolotherapy probably resulted in worse physical performance outcomes, compared with corticosteroid injections. Dextrose prolotherapy may improve pain-related functioning for lateral elbow tendinopathy and plantar fasciitis, compared with normal saline injections. Evidence on adverse events was generally lacking and severely limited by methodological concerns.

Musculoskeletal pain conditions are common among U.S. adults but can pose a challenge for patients and clinicians. Local injection therapies are often considered as treatment options for patients who have insufficient improvement in their symptoms from non-pharmacologic and topical or systemic pharmacologic therapies. Prolotherapy involves injecting an irritant solution into (intra-articular) or around (extra-articular) an affected structure to try to improve musculoskeletal pain and function. Hypertonic dextrose is the most commonly used prolotherapy solution.

In response to a request from VA's Pain Management, Opioid Safety and Prescription Drug Monitoring Program (PMOP) and Physical Medicine and Rehabilitation Services (PM&R), HSR's Evidence Synthesis Program (ESP) Center in Minneapolis conducted a systematic review on the evidence of the benefits and harms of dextrose prolotherapy for acute and chronic musculoskeletal pain conditions. VA PMOP and PM&R co-led an Integrated Project Team (IPT) on joint injectables for musculoskeletal pain, which consisted of clinicians with subject matter expertise in pain treatments, including dextrose prolotherapy. This IPT served as the technical expert panel for the review and advised on scope, key questions, eligibility criteria, and interpretation of findings. Results of the ESP review will support development of VA practice recommendations.

The review team searched for eligible studies in MEDLINE, Embase, and Scopus from inception to February 2024. Additional citations were identified from consultation with content experts, and from clinicaltrials.gov. Researchers identified 90 eligible studies — 80 randomized controlled trials and 10 observational studies. Eligible studies addressed a variety of musculoskeletal pain conditions, with about a quarter focused on knee osteoarthritis. Nearly a fifth of studies evaluated dextrose prolotherapy for temporomandibular joint (TMJ) dysfunction, while remaining studies addressed shoulder pain, pain due to lateral elbow tendinopathy, low back pain, plantar fasciitis, and a variety of other conditions.

Summary of Findings

• Of 90 eligible studies on dextrose prolotherapy, most were small and nearly half were rated as high risk of bias. Studies varied greatly in dextrose concentrations, injection technique, co-interventions, and comparators.
• Dextrose prolotherapy had varying efficacy across different musculoskeletal pain conditions.
• Evidence on adverse effects of dextrose prolotherapy was very uncertain for all included musculoskeletal pain conditions and comparators.
• For knee arthritis, intra-articular dextrose prolotherapy probably had little to no benefit for pain-related functioning or physical performance, compared with normal saline injections. The evidence was very uncertain on the effects of combined intra-articular and extra-articular dextrose prolotherapy on short- and medium-term pain-related functioning, but it may improve long-term outcomes, compared with normal saline injection or physical therapy and home exercise programs.
• For shoulder pain due to mixed bursitis and rotator cuff pathology, dextrose prolotherapy probably resulted in worse physical performance, compared with corticosteroid injection. The evidence was very uncertain on the benefit for pain-related functioning, and dextrose prolotherapy may have little to no benefit for physical performance, compared with normal saline injection.
• Dextrose prolotherapy may improve pain-related functioning for lateral elbow tendinopathy and plantar fasciitis, but the evidence was very uncertain for physical performance.
• For chronic low back pain, the evidence was very uncertain on the benefits of dextrose prolotherapy for pain-related functioning, compared with normal saline or corticosteroid injection.
• For TMJ disorders, the evidence was very uncertain on the benefits of dextrose prolotherapy, compared with normal saline or injections of blood from the individual’s body.

Implications

The evidence suggests that efficacy of dextrose prolotherapy may be condition specific. Whether certain populations and conditions benefit from dextrose prolotherapy, particularly compared with other non-surgical treatments, is an important area for future research. As the evidence is very uncertain for adverse effects of dextrose prolotherapy, more research is also needed to establish the safety of its use.

Limitations

• Studies were grouped together based primarily on comparator characteristics and consequently included a variety of dextrose concentrations and injection locations.
• A variety of physical therapy treatments and home exercise programs were grouped together as a similar comparator.
• Whenever possible, minimal clinically important differences were used to determine presence and direction of effects, but in a substantial number of instances, this review had to rely on statistical significance testing as reported by study authors.
• Eligibility was limited to studies written in English.

Future Research

Given the lack of efficacious therapies for musculoskeletal pain conditions, and interest in the potential benefits of dextrose prolotherapy, the efficacy and safety of dextrose prolotherapy should be explored more thoroughly in well-designed and rigorous clinical trials. Future studies of prolotherapy should be of sufficient size and methodological quality to systematically assess efficacy and safety compared with common conservative treatments, as well as appropriate placebo controls, given the likelihood of placebo effects associated with injection therapies for treating pain. More work is also needed to evaluate treatment costs and burden.

Citation: Ewart D, Sowerby C, Yang S, et al. Dextrose Prolotherapy for Musculoskeletal Pain: A Systematic Review. Washington, DC: Evidence Synthesis Program, Health Systems Research, Office of Research and Development, Department of Veterans Affairs. VA ESP Project #09-009; 2024.

To view the full report, go to vaww.hsrd.research.va.gov/publications/esp/dextrose-prolotherapy.cfm (intranet only).

ESP is currently soliciting review topics from the broader VA community. Nominations will be accepted electronically using the online Topic Submission Form. If your topic is selected for a synthesis, you will be contacted by an ESP Center to refine the questions and determine a timeline for the report.

This Management Brief is provided to inform you about recent HSR findings that may be of interest. The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs. If you have any questions or comments about this Brief, please email CIDER. The Center for Information Dissemination and Education Resources (CIDER) is a VA HSR Resource Center charged with disseminating important HSR findings and information to policy makers, managers, clinicians, and researchers working to improve the health and care of Veterans.

This report is a product of VA/HSR's Evidence Synthesis Program (ESP), which was established to provide timely and accurate synthesis of targeted healthcare topics of particular importance to VA managers and policymakers; and to disseminate these reports throughout VA.

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