BlueCross and BlueShield of Montana Medical Policy/Codes
Prolotherapy
Chapter: Medicine: Treatments
Current Effective Date: October 25, 2013
Original Effective Date: October 20, 2010
Publish Date: October 25, 2013
Revised Dates: April 14, 2010; October 18, 2010; September 30, 2013
Description

Prolotherapy describes a procedure for healing and strengthening lax ligaments by injecting proliferating agents and/or sclerosing solutions directly into partially torn or stretched ligaments or into a joint or adjacent structure(s) to create scar tissue in an effort to stabilize a joint. The goal of prolotherapy is to promote tissue repair or growth by prompting release of growth factors, such as cytokines, or by increasing the effectiveness of existing circulating growth factors. The mechanism of action is not well understood but may involve local irritation and/or cell lysis.

Prolotherapy may also be referred to as:

  • Proliferant injection,
  • “Prolo”,
  • Joint sclerotherapy,
  • Regenerative injection therapy,
  • Growth factor stimulation injection,
  • Ligamentous injection, or
  • Nonsurgical tendon, ligament, and joint reconstruction. 

Agents used with prolotherapy have included zinc sulfate, psyllium seed oil, dextrose, or dextrose in combination with glycerin, and/or phenol. Proliferatives act to promote tissue repair or growth by prompting release of growth factors, such as cytokines, or increasing the effectiveness of existing circulating growth factors. Polidocanol and sodium morrhuate, vascular sclerosants, have also been used to sclerose areas of high intratendinous blood flow associated with tendinopathies. Prolotherapy typically involves multiple injections per session conducted over a series of treatment sessions.

Policy

Each benefit plan, summary plan description or contract defines which services are covered, which services are excluded, and which services are subject to dollar caps or other limitations, conditions or exclusions. Members and their providers have the responsibility for consulting the member's benefit plan, summary plan description or contract to determine if there are any exclusions or other benefit limitations applicable to this service or supply.  If there is a discrepancy between a Medical Policy and a member's benefit plan, summary plan description or contract, the benefit plan, summary plan description or contract will govern.

Coverage

Prolotherapy is considered experimental, investigational and unproven for all indications including, but not limited to chronic neck or back pain, tendinopathy of the upper or lower limbs, osteoarthritic pain or other musculoskeletal pain conditions.

Policy Guidelines

HCPCS code M0076 specifically describes prolotherapy. Some practitioners submit non-specific CPT codes for prolotherapy, such as 20550, 20551, 20552, 20553, and 20999. The specific code for a service should be used when one is available.

Rationale

Prolotherapy has been investigated as a treatment of various etiologies of musculoskeletal pain, including arthritis, degenerative disc disease, fibromyalgia, tendonitis, and plantar fasciitis. As with any therapy for pain, a placebo effect is anticipated, and thus randomized placebo controlled trials are necessary to investigate the extent of the placebo effect and to determine whether any improvement with prolotherapy exceeds that associated with a placebo.  

This policy was originally created in 2010. When this policy was created, there was extensive literature regarding prolotherapy; however, a recent literature search revealed only four randomized placebo-controlled trials. This section of the current policy has been revised, and updated with searches of the MEDLINE database through June 2012. Following is a summary of the key literature to date

Chronic Neck and Back Pain

In 2004, a Cochrane review concluded that prolotherapy injections have not been proven to be more effective than placebo injections. (1)  Two 2005 reviews also noted that there was limited high-quality data to support prolotherapy and that the great variation in injection and treatment protocols limited interpretation of the data. (2, 3) An updated 2007 Cochrane review on prolotherapy for chronic low back pain concluded that “When used alone, prolotherapy is not an effective treatment for chronic low-back pain.” (4)  The authors also concluded that, although confounded by cointerventions and heterogeneity of studies, “When combined with spinal manipulation, exercise, and other interventions, prolotherapy may improve chronic low-back pain and disability.” A 2008 systematic review (of the same five studies included in the Cochrane review and by one of the same authors) concluded that despite its use for more than 50 years, there is no evidence of efficacy for prolotherapy injections alone for chronic low back pain. (5)  The same evidence was evaluated in a 2009 systematic review conducted for the American Pain Society. (6)  The authors of this review concluded that prolotherapy was found to be ineffective when used alone for chronic low back pain.

Three randomized trials were identified that focused on the use of injections of dextrose, glycerin, and phenol as a treatment of low back pain. In 1987, Ongley et al. reported on a trial of 81 patients with low back pain who were randomly assigned to receive spinal manipulation plus prolotherapy compared to a control group that received less forceful spinal manipulation, less local anesthesia, and placebo injections of saline. (7)  Although improved responses were reported for the treatment group, it is not possible to isolate the possible contribution of the prolotherapy compared to the impact of the different types of spinal manipulation.

In 1993, Klein and colleagues reported on a trial that randomly assigned 79 patients with low back pain to receive a series of six weekly injections using either saline or a proliferant solution of dextrose, glycerine, and phenol. (8)  Thirty of the 39 patients assigned to the proliferant group achieved a 50% or greater diminution in pain compared to 21 of the 40 in the placebo group. While the incremental benefit of the treatment group was statistically significant (p=0.04), blinding of the treatment groups was not maintained, since those assigned to the proliferant group experienced a clinically recognizable local inflammatory response.

In 2004, Yelland and colleagues reported on a randomized, partially blinded, controlled trial on prolotherapy injections, saline injections, and exercises for chronic low back pain in 110 subjects. (9)  While decreases in pain and disability were noted in all study groups, there were no significant differences found between treatment groups at 12 and 24 months. Therefore, the effects of prolotherapy did not significantly exceed placebo effects.

Dagenais and colleagues also conducted a survey of practitioners of prolotherapy for back and neck pain. (10)  Completed surveys (n=171, 50% response rate) revealed that practitioners had a median of 10 years of experience, with a median 2,000 treatments in 500 patients. About 500 adverse events (25% of treatments) were reported; 69 (14% of patients) required hospitalization. Adverse events included spinal disc injury, hemorrhage, infection, nerve damage, pneumothorax, spinal headache, spinal cord insult, and systemic reactions. The efficacy of prolotherapy for chronic neck and back pain has not been demonstrated; this procedure is considered experimental, investigational and unproven.

Osteoarthritis

In 2000, Reeves and Hassanein reported on two trials that used dextrose for the treatment of osteoarthritis. (11)  The first trial randomly assigned 68 patients with 111 osteoarthritic knees to receive either three bimonthly injections of dextrose or placebo. The patients were evaluated with a visual analog scale (VAS) for pain and swelling, frequency of leg buckling, goniometrically measured flexion, and radiographic measures of joint narrowing. As the data are presented, it is clear that there was significant improvement in both the placebo and treatment groups, but it is difficult to determine the comparative magnitude of improvement between the two groups. For example, for the various outcome measures of pain, it appears that there are probably no clinically significant incremental effects of prolotherapy compared to the placebo group. However, for other non-pain outcomes, i.e., swelling; buckling; and flexion range, prolotherapy may be associated with a significant incremental improvement. The various outcome measures were combined and assessed using a Hotelling multivariate analysis. With this statistical measurement, prolotherapy demonstrated a statistically superior overall effect (p=0.015) compared to the control group. It should be recognized that the statistical significance of this measure is most likely due to the improvements in the non-pain symptoms (i.e., swelling, buckling, and flexion range). In summary, it is not known whether the incremental improvement in the non-pain-related outcomes of the prolotherapy group compared to the control group is clinically significant.

In a similarly designed study, the same investigators studied the effectiveness of prolotherapy as a treatment of osteoarthritic thumb and finger joints. (12)  A total of 27 patients with 150 osteoarthritic joints were randomly assigned to receive three bimonthly injections of either dextrose or water. Patients were evaluated with both VAS for pain and goniometric assessment of joint movement. Since patients had a variable number of joints injected (ranging from 1 to 22), the VAS score for every symptomatic joint in each patient was added together for a total and divided by the number of symptomatic joints to provide an average joint pain score for each patient. There were improvements in pain scores in both the placebo and treatment groups, but the incremental improvement of the treatment group compared to the placebo group did not reach statistical significance. In terms of flexion, the treatment group reported a statistically significant improvement (p=0.043), while the placebo group reported a greater, statistically significant decrease (p=0.011). Therefore, the statistically significant difference in flexion between the two groups (p=0.003) was primarily related to the decrease in the control group, with a smaller contribution related to the positive response in the treatment group. In summary, the clinical significance of an isolated finding of improved flexion without a corresponding significant improvement in pain is uncertain.

Tendinopathies of the Upper and Lower Limbs

A 2009 systematic review evaluated injection therapies for lateral epicondylitis (tennis elbow); two randomized controlled trials and one prospective case series on prolotherapy were included. (13)  One of the randomized trials was referenced as a report from a 2006 conference on complementary and alternative medicine; no authors are listed in the reference, and the study does not appear to be available in the peer-reviewed published literature. The second randomized double-blind placebo-controlled trial involved 20 patients who had elbow pain for at least six months and failure of conservative therapy (rest, physical therapy, nonsteroidal anti-inflammatory drugs, and two corticosteroid injections) to three treatments (over eight weeks) of prolotherapy or saline injection. (14)  There was a significant improvement in pain with prolotherapy injection (from 5.1 to 0.5 on a Likert scale) in comparison with saline injection (4.5 to 3.5). Isometric strength also improved (13 to 31 lb vs. 10 to 11 lb, respectively), but there was no difference in grip strength between the two conditions. The authors indicated that this is the first randomized trial of prolotherapy for tendinopathy and that additional research with a larger study population is needed.

Yelland et al., an author of Cochrane reviews on this topic, reported a multicenter randomized trial of prolotherapy or exercises for Achilles tendonitis in 43 patients. (15)  Inclusion criteria were diagnosis of unilateral or bilateral mid-portion Achilles tendinosis with pain between 2 and 7 centimeters proximal to the calcaneal attachment in adults older than 18 years with activity-related pain for at least six weeks. The sample size was limited by the available resources and slow recruitment rate, resulting in 15 participants in the eccentric loading exercise group, 14 in the prolotherapy group, and 14 in the combined treatment group. Randomization was conducted by a central site and resulted in a lower median duration of pain in the combined treatment group (six months) than in the exercise alone (21 months) or prolotherapy alone (24 months) groups. An average of 4.4 injections per treatment was directed at tender points in the subcutaneous tissues adjacent to the affected tendon, with four to 12 weekly treatments until the participants attained pain-free activity or requested to cease treatment. The participants were instructed to perform eccentric loading exercises twice daily in three sets of 15 repetitions with the knee straight and three sets of 15 repetitions with the knee bent for a period of 12 weeks, with the load progressively increased by adding weights to a backpack. Clinical reviews were performed at three, six, and 12 weeks to check technique and progress. Mean increases in the validated Victorian Institute of Sport Assessment – Achilles (VISA-A) score were 23.7 for exercise alone, 27.5 for prolotherapy alone, and 41.1 for the combined treatment. At six weeks and 12 months, these increases were significantly greater for combined treatment (exercise and prolotherapy) than for exercise alone. The predefined minimum clinically important increase of 20 points or more on the VISA-A was obtained by 12 subjects in the combined treatment group and 11 each in the exercise alone and prolotherapy alone groups. This was not significantly different. The percentage of patients achieving full recovery (VISA-A score of 90 or above at 12 months) was 53% for exercise alone, 71% for prolotherapy alone, and 64% for the combined treatment group, but these differences were not significant. Although the authors concluded that prolotherapy may be a cost-effective method to speed recovery in patients with Achilles tendonitis, this study is limited by the combination of a small number of subjects per group, unequal duration of pain in the treatment groups at baseline, and minimal differences in the number of patients showing recovery (11 vs. 12, of 14 or 15, respectively). Additional randomized trials are needed to replicate and extend these findings.

Other Musculoskeletal Pain

Reeves and Hassanein reported on a study of dextrose prolotherapy for anterior cruciate ligament (ACL) laxity. (16)  Of 16 evaluable patients, statistically significant improvements were found at six, 12, and 36 months in ACL laxity, pain, swelling, and knee range of motion  However, this was a small, nonrandomized trial and, as noted above, without placebo control, the extent that improvements with prolotherapy exceed those associated with a placebo cannot be determined.

A 2010 publication by Kim et al. compared intra-articular prolotherapy with intra-articular corticosteroid injection for sacroiliac pain. (17)  The randomized double-blind study included 48 patients with sacroiliac joint pain lasting equal to or greater than three months, confirmed by equal to or greater than 50% improvement in response to local anesthetic block  The injections were performed on a biweekly schedule (maximum of three injections) under fluoroscopic guidance with confirmation of the intra-articular location with an arthrogram. Pain and disability scores were assessed at baseline, two weeks, and monthly after completion of treatment. At two weeks after treatment, all patients met the primary outcome measure of equal to or greater than 50% reduction in pain scores, and there was no significant difference between the two groups. The numerical rating scale for pain was reduced from 6.3 to 1.4 in the prolotherapy group and from 6.7 to 1.9 in the steroid group. The Oswestry Disability Index (ODI) decreased from 33.9 to 11.1 in the prolotherapy group and from 35.7 to 15.5 in the steroid group. Kaplan-Meier survival analysis showed a significantly greater percentage of patients with sustained relief following prolotherapy. At six months after treatment, 63.6% of patients in the prolotherapy group reported equal to or greater than 50% improvement from baseline in comparison with 27.2% of the steroid group. At 15 months after treatment, 58.7% of patients in the prolotherapy group reported relief equal to or greater than 50% in comparison with 10.2% of the steroid group. Key differences between this and other studies on prolotherapy were the selection of patients using a diagnostic sacroiliac joint block and the use of an arthrogram to confirm the location of the injection. Additional trials are needed to confirm the safety and efficacy of this procedure.

Ongoing Clinical Trials

A search of online site ClinicalTrials.gov in June 2012 identified several ongoing or completed randomized trials or non-randomized studies on prolotherapy:

  • Joint Injections for Osteoarthritic Knee Pain (NCT00085722) is listed as ongoing but is currently not recruiting participants. This randomized placebo-controlled study is sponsored by the National Center for Complementary and Alternative Medicine (NCCAM) and will determine whether prolotherapy can decrease pain and disability from knee osteoarthritis. The posting lists an estimated enrollment of 111 subjects, with November 2009 as the completion date for primary outcome measures. (18)
  • Efficacy Study of Prolotherapy vs Corticosteroid for Tennis Elbow (NCT00160303 is listed as completed, but no study reports have been posted. The study is sponsored by Spaulding Rehabilitation Hospital. This randomized double-blinded controlled trial is a phase III. The number of subjects was not listed in the posting. The completion date was December 2006. (19)
  • Prolotherapy for the Treatment of Chronic Lateral Epicondylitis (NCT00674622) is a randomized placebo-controlled trial sponsored by NCCAM. It is described as ongoing but not currently recruiting participants. There is an estimated enrollment of 60 subjects with a completion date of September 2010. (20)
  • The Effect of Prolotherapy on Balance and Lumbar Flexibility in the Patients With a Sacralized L5 Vertebra (NCT01177449) is an open label study to evaluate for ability on balance and lumbar flexibility, which will include a sensory organization test, and rhythmic weight shifting and limits of stability assessments. The study was sponsored by Chang Gung Memorial Hospital and the completion date was August 2010, but no study reports have been posted.  The number of subjects was not listed in the description. (21)
  • Prolotherapy for the Treatment of Plantar Fasciitis (NCT01326351) is described as a Phase IV randomized double-blind sham controlled trial of prolotherapy combined with a physiotherapy program for plantar fasciitis. The study is sponsored by Réseau de Santé Vitalité Health Network in Canada. The posting lists an estimated enrollment of 60 subjects with completion expected in February 2012. (22)
  • Study of 25% Dextrose Injections in Shoulder Ligaments and Tendons to Promote Their Healing (Prolotherapy) (NCT01402011) is listed as ongoing but currently not recruiting participants. This randomized placebo-controlled study is sponsored by the University of British Columbia and will determine whether prolotherapy can decrease pain, increase functional capacity and promotes healing better and in less time than standard physiotherapy treatment. The posting lists an enrollment of 75 subjects, with October 2012 as the completion date for primary outcome measures. (23)
  • Efficacy of Injection Therapy for Lateral Epicondylosis (NCT01476605) is listed as ongoing but currently not recruiting participants. This randomized open label pilot study is sponsored by the University of Wisconsin, in Madison. The purpose of this study is to assess two prolotherapy solutions commonly used in the treatment of moderate-to-severe tennis elbow using clinical, biomechanical and radiological outcomes. The estimated enrollment is 40 subjects with the primary completion date of July 2012. (24)

Summary

The literature on prolotherapy consists of small randomized trials on a variety of pain syndromes, with inconsistent results. The body of scientific evidence does not permit conclusions concerning the effect of prolotherapy on health outcomes for chronic neck or back pain, tendinopathies of the upper or lower limbs, osteoarthritic pain, or other musculoskeletal pain conditions. Therefore, prolotherapy is considered experimental, investigational and unproven.

Coding

Disclaimer for coding information on Medical Policies           

Procedure and diagnosis codes on Medical Policy documents are included only as a general reference tool for each policy. They may not be all-inclusive.           

The presence or absence of procedure, service, supply, device or diagnosis codes in a Medical Policy document has no relevance for determination of benefit coverage for members or reimbursement for providers. Only the written coverage position in a medical policy should be used for such determinations.           

Benefit coverage determinations based on written Medical Policy coverage positions must include review of the member’s benefit contract or Summary Plan Description (SPD) for defined coverage vs. non-coverage, benefit exclusions, and benefit limitations such as dollar or duration caps. 

ICD-9 Codes
81.92.  Experimental, investigational and unproven for all diagnoses.
ICD-10 Codes
3E0U.  Experimental, investigational and unproven for all diagnoses.
Procedural Codes: 20550, 20551, 20552, 20553, 20999, M0076
References
  1. Yelland, M.J., Mar, C., et al. Prolotherapy injections for chronic low-back pain. Cochrane Database of Systematic Reviews (2004) (2):CD004059.
  2. Dagenais, S., Haldeman, S., et al. Intraligamentous injection of sclerosing solution (prolotherapy) for spinal pain:  a critical review of the literature. The Spine Journal (2005 May-June) 5(3):310-28.
  3. Rabago, D., Best, T.M., et al. A systematic review of prolotherapy for chronic musculoskeletal pain. Clinical Journal of Sport Medicine (2005 September) 5(5):376-80.
  4. Dagenais, S., Yelland, M.J., et al. Prolotherapy injections for chronic low-back pain. Cochrane Database of Systematic Reviews. (2007 April) (2):CD004059.
  5. Dagenais, S., Mayer, J., et al. Evidence-informed management of chronic low back pain with prolotherapy. Spine Journal (2008 January-February) 8(1):203.12.
  6. Chou, R., Atlas, S.J., et al. Nonsurgical interventional therapies for low back pain: a review of the evidence for an American Pain Society clinical practice guideline. Spine (Philadelphia, Pa 1976) (2009 May 1) 34(10):1078-93.
  7. Ongley, M.J., Klein R.G., et al. A new approach to the treatment of chronic low back pain. Lancet (1987 July 18) 2(8551):143-6.
  8. Klein, R.G., Eek, B.C., et al.  A randomized double-blind trial of dextrose-glycerine-phenol injections for chronic, low back pain. Journal of Spinal Disorders (1993 February) 6(1):23-33.
  9. Yelland, M.J., Glasziou, P.P., et al. Prolotherapy injections, saline injections, and exercises for chronic low-back pain: a randomized trial. Spine (Philadelphia, Pa 1976) (2004 January 1) 29(1):9-16; discussion 16.
  10. Dagenais, S., Ogunseitan, O., et al. Side effects and adverse events related to intraligamentous injection of sclerosing solutions (prolotherapy) for back and neck pain: a survey of practitioners. Archives of Physical Medicine and Rehabilitation (2006 July) 87(7):909-13.
  11. Reeves, K.D., and K. Hassanein. Randomized prospective double-blind placebo-controlled study of dextrose prolotherapy for knee osteoarthritis with or without ACL laxity. Alternative Therapies in Health and Medicine (2000 March) 6(2):68-74, 77-80.
  12. Reeves K.D., and K. Hassanein. Randomized, prospective, placebo-controlled double-blind study of dextrose prolotherapy for osteoarthritic thumb and finger (DIP, PIP, and trapeziometacarpal) joints: evidence of clinical efficacy. Journal of Alternative and Complementary Medicine (2000 August) 6(4):311-20.
  13. Rabago, D.P., Best, T.M., et al. A systematic review of four injection therapies for lateral epicondylosis: prolotherapy, polidocanol, whole blood and platelet-rich plasma. British Journal of Sports Medicine (2009 July) 43(7):471-81.
  14. Scarpone, M., Rabago, D.P., et al. The efficacy of prolotherapy for lateral epicondylosis; a pilot study.  Clinical Journal of Sport Medicine (2008 May) 18(3):248-54.
  15. Yelland, M.J., Sweeting, K.R., et al. Prolotherapy injections and eccentric loading exercises for painful Achilles tendinosis: a randomized trial. British Journal of Sports Medicine (22 June 2009) 45(5):421-8. 
  16. Reeves, K.D., and K.M. Hassanein. Long-term effects of dextrose prolotherapy for anterior cruciate ligament laxity. Alternative Therapies in Health and Medicine (2003 May-June) 9(3):58-62.
  17. Kim, W.M., Lee, H.G., et al. A randomized controlled trial of intra-articular prolotherapy versus steroid injection for sacroiliac joint pain. Journal of Alternative and Complementary Medicine (2010 December) 16(12):1285-90.
  18. NIH – Joint injections for osteoarthritic knee pain (NCT00085722). U.S. National Institutes of Health (2004 June 14). Available at http://www.clinicaltrials.gov (accessed – 2012 July 2).
  19. NIH – Efficacy study of prolotherapy vs corticosteroid for tennis elbow (NCT00160303). U.S. National Institutes of Health (2005 September8). Available at http://www.clinicaltrials.gov (accessed – 2012 July 2).
  20. NIH – Prolotherapy for the treatment of chronic lateral epicondylitis (NCT00674622). U.S. National Institutes of Health (2008 May 6). Available at http://www.clinicaltrials.gov (accessed – 2012 July 2).
  21. NIH – The effect of prolotherapy on balance and lumbar flexibility in the patients with a sacralized L5 vertebra (NCT01177449). U.S. National Institutes of Health (2010 August 5). Available at http://www.clinicaltrials.gov (accessed – 2012 July 2).
  22. NIH – Prolotherapy for the treatment of plantar fasciitis (NCT01326351). U.S. National Institutes of Health (2011 March 29). Available at http://www.clinicaltrials.gov (accessed – 2012 July 2).
  23. NIH – Study of 25% dextrose injections in shoulder ligaments and tendons to promote their healing (prolotherapy) (NCT00085722). U.S. National Institutes of Health (2011 June 20). Available at http://www.clinicaltrials.gov (accessed – 2012 July 2).
  24. NIH – Efficacy of injection therapy for lateral epicondylosis (NCT01476605). U.S. National Institutes of Health (2011 October 25). Available at http://www.clinicaltrials.gov (accessed – 2012 July 2).
  25. Prolotherapy.  Chicago, Illinois: Blue Cross Blue Shield Association Medical Policy Reference Manual (2011 August) Medicine 2.01.26.
History

April 2010  Physician's Advisory Committee (PAC) meeting/approved 
October 2012 Policy updated with literature review through June 2012.  References 15 and 17 added.  Policy statement unchanged. 
October 2013 Policy formatting and language revised.  Policy statement unchanged.  Added CPT codes 20550, 20551, 20552, 20553, and 20999.

BCBSMT Home
®Registered marks of the Blue Cross and Blue Shield Association, an association of independent Blue Cross and Blue Shield Plans. ®LIVE SMART. LIVE HEALTHY. is a registered mark of BCBSMT, an independent licensee of the Blue Cross and Blue Shield Association, serving the residents and businesses of Montana.
CPT codes, descriptions and material only are copyrighted by the American Medical Association. All Rights Reserved. No fee schedules, basic units, relative values or related listings are included in CPT. The AMA assumes no liability for the data contained herein. Applicable FARS/DFARS Restrictions Apply to Government Use. CPT only © American Medical Association.
Prolotherapy