| MP 2.01.26 | Prolotherapy | |
| Medical Policy | ||
| Section Medicine |
Subsection | Last Review Status/Date Reviewed with literature search/8:2009 |
| Issue 8:2009 |
Original Policy Date 5/30/97 |
Return to Medical Policy Index |
Disclaimer
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.
Description
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.
The goal of prolotherapy is to promote tissue repair or growth by prompting release of growth factors, such as cytokines, or 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. Agents used with prolotherapy have included zinc sulfate, psyllium seed oil, combinations of dextrose, glycerine, and phenol, or dextrose alone, often combined with a local anesthetic. 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. A similar approach involves the injection of autologous platelet-rich plasma (PRP), which contains a high concentration of platelet-derived growth factors. Treatment of musculoskeletal pain conditions (e.g., tendinopathies) with PRP is discussed in policy No 2.01.16.Policy
Prolotherapy is considered investigational as a treatment of musculoskeletal pain.
Policy Guidelines
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)
Benefit Application
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.
Rationale
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, through June 2009, identified one new randomized trial and 3 systematic reviews. Relevant literature is discussed below.
Literature Review
Chronic Neck and Back Pain
In 2004, a Cochrane review concluded prolotherapy injections have not been proven to be more effective than placebo injections. (1) Two other 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 co-interventions 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 5 studies included in the Cochrane review and by one of the same authors) concluded that despite its use for over 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 randomized 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 randomized 79 patients with low back pain to receive a series of 6 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 disk 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 investigational.
Osteoarthritis
In 2000, Reeves and Hassanein reported on 2 trials that used dextrose for the treatment of knee osteoarthritis. (11) The first trial randomized 68 patients with 111 osteoarthritic knees to receive either 3 bimonthly injections of dextrose or placebo. The patients were evaluated with a visual analogue 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 2 groups. For example, for the various outcome measures ofpain, 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 randomized to receive 3 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 2 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 epicondylosis (tennis elbow); 2 randomized controlled trials and 1 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 6 months and failure of conservative therapy (rest, physical therapy, nonsteroidal anti-inflammatory drugs, and 2 corticosteroid injections) to 3 treatments (over 8 weeks) of prolotherapy or saline injection. (14) There was a significant improvement in pain (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 31lb vs. 10 to 11 lb), 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 multi-center 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 over 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, out of 14 or 15). 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 6, 12, and 36 months in ACL laxity, pain, swelling, and knee range of motion. However, this was a small, non-randomized trial and, as noted above, without placebo-control, the extent that improvements with prolotherapy exceed those associated with a placebo cannot be determined.
Summary
The 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, the policy statement is unchanged.
Medicare National Coverage
The Coverage Issues Manual section 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. (17) In 1999, on request for reconsideration for coverage of prolotherapy for treatment for chronic low back pain, Medicare retained its decision for non-coverage of prolotherapy again, citing a lack of scientific evidence on which to base a decision. (18)
References:
- 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.
- 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. 2009 Jun 22. [Epub ahead of print]
- Reeves KD, Hassanein KM. Long-term effects of dextrose prolotherapy for anterior cruciate ligament laxity. Altern Ther Health Med 2003; 9(3): 58-62.
- http://cms.hhs.gov/manuals/06_cim/ci35.asp#_1_14.
- http://cms.hhs.gov/coverage/8b3-l2.asp.
Codes |
Number |
Description |
CPT |
|
See policy guidelines |
ICD-9 Procedure |
81.92 |
Injection of therapeutic substance into joint or ligament |
ICD-9 Diagnosis |
|
investigational for all codes |
HCPCS |
M0076 |
Prolotherapy |
Type of Service |
Medicine |
|
Place of Service |
Physician’s Office |
|
Index
Prolotherapy
Policy History
| Date | Action | Reason |
| 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 |
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