|Subsection||Last Review Status/Date
Reviewed with literature search/8:2012
|Original Policy Date
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Our medical policies are designed for informational purposes only and are not an authorization, or an explanation of benefits, or a contract. Receipt of benefits is subject to satisfaction of all terms and conditions of the coverage. Medical technology is constantly changing, and we reserve the right to review and update our policies periodically.
Prolotherapy describes a procedure intended for healing and strengthening ligaments and tendons by injecting an agent that induces inflammation and stimulates endogenous repair mechanisms. Prolotherapy may also be referred to as proliferant injection, prolo, joint sclerotherapy, regenerative injection therapy, growth factor stimulation injection, or nonsurgical tendon, ligament and joint reconstruction.
Prolotherapy is considered investigational as a treatment of musculoskeletal pain.
HCPCS code M0076 code specifically describes prolotherapy.
However, providers may be using one of the following nonspecific CPT codes:
20550: injection)s); single tendon sheath, or ligament, aponeurosis
20551: Injection(s); single tendon orogin/insertion
20552: Injection(s); single or multiple trigger point(s), one or two muscle(s)
20999: Unlisted procedure, musculoskeletal system, general
27096: Injection procedure fr sacroiliac joint, arthrography and/or anesthetic/steroid
64475: Injection, anesthetic agent and/pr steroid, paravertebral facet joint nerve; lumbar or sacral single level (with 64476 for each additional level)
BlueCard/National Account Issues
Plans may wish to consider retrospective review of claims for injections (i.e., CPT code 20550) focusing on the agents used in the injection.
Prolotherapy has been investigated as a treatment of various etiologies of musculoskeletal pain, including arthritis, degenerative disc disease, fibromyalgia, tendinitis, 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. When the policy was created there was extensive literature regarding prolotherapy, however, a literature search revealed only 4 randomized placebo-controlled trials. The literature has been updated periodically with searches of the MEDLINE database. The most recent update was performed through May 2011. Relevant literature is discussed below.
A small (17 subjects) randomized double-blind trial of prolotherapy versus corticosteroid injections for chronic lateral epicondylitis was reported in 2011. (15) Each subject received an injection at baseline followed by a second injection at 1 month. VAS for pain, quadruple VAS (QVAS), and Disabilities of the Arm, Shoulder, and Hand questionnaire (DASH) were measured at baseline and at 1, 3, and 6 months. A change of 2 for VAS and 12 for DASH was considered clinically significant. Per protocol analysis showed a significant improvement in VAS and DASH at both 3 (2.38 and 19.89) and 6 months (2.63 and 21.76, both respectively) for the prolotherapy group, while the corticosteroid group showed significant improvement on the DASH at 3 (13.33) and 6 months (15.56). The study was underpowered to detect a significant difference between the prolotherapy and corticosteroid groups for change in VAS, QVAS, or DASH. Larger controlled trials are needed.
Achilles Tendonitis. 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. (16) Inclusion criteria were diagnosis of unilateral or bilateral mid-portion Achilles tendinosis with pain between 2 and 7 cm proximal to the calcaneal attachment in adults older than 18 years with activity-related pain for at least 6 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 (6 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 4 to 12 weekly treatments until participants attained pain-free activity or requested to cease treatment. The participants were instructed to perform eccentric loading exercises twice daily in 3 sets of 15 repetitions with the knee straight and 3 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 3, 6, 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 6 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. (17) Of 16 evaluable patients, statistically significant improvements were found at 6, 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. (18) The randomized double-blind study included 48 patients with sacroiliac joint pain lasting equal to or greater than 3 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 3 injections) under fluoroscopic guidance with confirmation of the intra-articular location with an arthrogram. Pain and disability scores were assessed at baseline, 2 weeks, and monthly after completion of treatment. At 2 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 2 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 6 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 July 2012 identified the following randomized trials on prolotherapy:
- The Efficacy of Prolotherapy in 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 July 2012 as the completion date for primary outcome measures.
- Prolotherapy for the Treatment of Chronic Lateral Epicondylitis (NCT00674622) is a randomized placebo-controlled trial sponsored by NCCAM. The study is listed as completed as of June 14, 2012 with 67 subjects.
- 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 2012. Recruitment for this study had not begun as of April 2011.
- NCT01402011 is a randomized study of prolotherapy for injured ligaments and tendons of the shoulder. The study is currently recruiting participants and has an estimated enrollment of 74 subjects with completion expected in 2013.
- NCT01617356 is a randomized trial of prolotherapy versus saline injection for the treatment of temporomandibular dysfunction. The study began enrollment of a projected 42 subjects in June 2012 and has an estimated study completion date in 2014.
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 investigational.
Medicare National Coverage
The Coverage Issues Manual (CIM) #35-13 states that prolotherapy, joint sclerotherapy, and ligamentous injections with sclerosing agents are not covered, noting that the medical effectiveness of these therapies has not been verified by scientifically controlled studies. In 1999, on request for reconsideration of coverage of prolotherapy for treatment for chronic low back pain, Medicare retained its decision for noncoverage of prolotherapy again, citing a lack of scientific evidence on which to base a decision. (19)
- Yelland MJ, Mar C, Pirozzo S et al. Prolotherapy injections for chronic low-back pain. Cochrane Database Syst Rev 2004; (2):CD004059.
- Dagenais S, Haldeman S, Wooley JR. Intraligamentous injection of sclerosing solution (prolotherapy) for spinal pain: a critical review of the literature. Spine J 2005; 5(3):310-28.
- Rabago D, Best TM, Beamsley M et al. A systematic review of prolotherapy for chronic musculoskeletal pain. Clin J Sport Med 2005; 15(5):376-80.
- Dagenais S, Yelland M, Del Mar C et al. Prolotherapy injections for chronic low-back pain. Cochrane Database Syst Rev. 2007; (2):CD004059.
- Dagenais S, Mayer J, Haldeman S et al. Evidence-informed management of chronic low back pain with prolotherapy. Spine J 2008; 8(1):203-12.
- Chou R, Atlas SJ, Stanos SP et al. Nonsurgical interventional therapies for low back pain: a review of the evidence for an American Pain Society clinical practice guideline. Spine 2009; 34(10):1078-93.
- Ongley MJ, Klein RG, Dorman TA et al. A new approach to the treatment of chronic low back pain. Lancet 1987; 2(8551):143-6.
- Klein RG, Eek BC, DeLong WB et al. A randomized double-blind trial of dextrose-glycerine-phenol injections for chronic, low back pain. J Spinal Disord 1993; 6(1):23-33.
- Yelland MJ, Glasziou PP, Bogduk N et al. Prolotherapy injections, saline injections, and exercises for chronic low-back pain: a randomized trial. Spine 2004; 29(1):9-16.
- Dagenais S, Ogunseitan O, Haldeman S et al. Side effects and adverse events related to intraligamentous injection of sclerosing solutions (prolotherapy) for back and neck pain: a survey of practitioners. Arch Phys Med Rehabil 2006; 87(7):909-13.
- Reeves KD, Hassanein K. Randomized prospective double-blind placebo-controlled study of dextrose prolotherapy for knee osteoarthritis with or without ACL laxity. Altern Ther Health Med 2000; 6(2):68-74, 77-80.
- Reeves KD, Hassanein K. Randomized, prospective, placebo-controlled double-blind study of dextrose prolotherapy for osteoarthritic thumb and finger (DIP, PIP, and trapeziometacarpal) joints: evidence of clinical efficacy. J Altern Complement Med 2000; 6(4):311-20.
- Rabago D, Best TM, Zgierska A et al. A systematic review of four injection therapies for lateral epicondylosis: prolotherapy, polidocanol, whole blood and platelet rich plasma. Br J Sports Med 2009 Jan 21. [Epub ahead of print].
- Scarpone M, Rabago DP, Zgierska A et al. The efficacy of prolotherapy for lateral epicondylosis: a pilot study. Clin J Sport Med 2008; 18(3):248-54.
- Carayannopoulos A, Borg-Stein J, Sokolof J et al. Prolotherapy versus corticosteroid injections for the treatment of lateral epicondylosis: a randomized controlled trial. PMR 2011; 3(8):706-15.
- Yelland MJ, Sweeting KR, Lyftogt JA et al. Prolotherapy injections and eccentric loading exercises for painful Achilles tendinosis: a randomised trial. Br J Sports Med 2011; 45(5):421-8.
- Reeves KD, Hassanein KM. Long-term effects of dextrose prolotherapy for anterior cruciate ligament laxity. Altern Ther Health Med 2003; 9(3):58-62.
- Kim WM, Lee HG, Jeong CW et al. A randomized controlled trial of intra-articular prolotherapy versus steroid injection for sacroiliac joint pain. J Altern Complement Med 2010; 16(12):1285-90.
- Centers for Medicare and Medicaid Services. National Coverage Determination (NCD) for PROLOTHERAPY, Joint Sclerotherapy, and Ligamentous Injections with Sclerosing Agents (150.7). 1999. Available online at: http://www.cms.gov/medicare-coverage-database/search/document-id-search-results.aspx?DocID=150.7&ncd_id=150.7&ncd_version=1&basket=ncd%253A150%252E7%253A1%253AProlotherapy%257C%257C+Joint+Sclerotherapy%257C%257C+and+Ligamentous+Injections+with+Sclerosing+Agents&bc=gAAAAAAAAAAA&. Last accessed July, 2012.
See policy guidelines
Injection of therapeutic substance into joint or ligament
investigational for all codes
|ICD-10-CM (effective 10/1/13)||Investigational for all diagnoses|
|ICD-10-PCS (effective 10/1/13)||3E0233Z, 3E0236Z, 3E023BZ, 3E023GC, 3E023NZ, 3E023TZ||Administration, introduction, muscle, percutaneous, code list – code selection depends on substance injected|
|3E0U33Z, 3E0U36Z, 3E0U3BZ, 3E0U3GC, 3E0U3NZ, 3E0U3TZ||Administration, introduction, joints, percutaneous, code list – code selection depends on substance injected|
Type of Service
Place of Service
|5/30/97||Add to Medicine section||New policy|
|8/15/01||Replace policy||Policy reviewed; policy statement unchanged. New references included|
|11/22/02||Replace policy||Literature review update; added Medicare Policy to rationale section; no change in policy statement|
|04/29/03||Replace policy||Policy updated; policy statement unchanged|
|02/25/04||Replace policy||Policy updated with literature review; policy statement unchanged|
|05/23/05||Replace policy||Literature review update for the period of 2004 through March 2005; references added. Policy statement unchanged|
|04/25/06||Replace policy||Policy updated with literature review; policy statement unchanged. Reference numbers 10 and 11 added|
|06/14/07||Replace policy||Policy updated with literature review; references 12 and 13 added; policy statement unchanged.|
|07/10/08||Replace policy||Policy updated with literature review; references 14 and 15 added; policy statement unchanged|
|08/13/09||Replace policy||Policy updated with literature review through June 2009; Rationale section revised; references added and reordered; policy statement unchanged|
|08/12/10||Replace policy||Policy updated with literature review through June 2010; policy statement unchanged|
|8/11/11||Replace policy||Policy updated with literature review through May 2011; reference 17 added; policy statement unchanged|
|8/09/12||Replace policy||Policy updated with literature review through June 2012; reference 15 added; policy statement unchanged|