Medical Policy


Subject: Prolotherapy for Joint and Ligamentous Conditions
Document #: MED.00007 Publish Date:    04/25/2018
Status: Reviewed Last Review Date:    03/22/2018


This document addresses the use of prolotherapy for the treatment of musculoskeletal pain and ligament instability.

Position Statement

Investigational and Not Medically Necessary:

Prolotherapy, joint sclerotherapy and reconstructive ligament therapy with injections of sclerosing agents are considered investigational and not medically necessary for all conditions.


Prolotherapy, also referred to as joint sclerotherapy or reconstructive ligament therapy, has been investigated as a treatment of various sources of musculoskeletal pain, including arthritis, chronic neck and back pain, degenerative disc disease, fibromyalgia, tendonitis and ligamentous instability.

Chronic Neck and Back Pain

Although there is extensive literature regarding the use of prolotherapy for joint pain, the earliest evidence in the peer-reviewed medical literature for back pain consists of small randomized, placebo-controlled trials. The treatment group in one trial for chronic low back pain included both spinal manipulation and prolotherapy. While positive results were reported in the treatment group, it is not possible to determine the independent effect of prolotherapy (Yelland, 2004a; 2004b; 2004c). In another trial, the treatment group was not effectively blinded from the placebo group (Wilkinson, 2005).

Other evidence in the peer-reviewed medical literature evaluating prolotherapy injections consists of case series and systematic reviews (Dagenais, 2005; Kim, 2004; Rabago, 2005; Watson, 2010). A systematic review by Dagenais and colleagues (2008) concluded “that despite its use for over 50 years, there is no evidence of efficacy for prolotherapy injections alone for chronic low back pain.” A 2009 systematic review performed for the American Pain Society concluded that prolotherapy was found to be ineffective when used alone for chronic low back pain (Chou, 2009).


In 2000, two randomized, placebo-controlled trials were published that were effectively blinded and isolated the contribution of prolotherapy. One trial focused on osteoarthritis of the knees (Reeves, 2000a) while the other focused on osteoarthritis of the thumb and finger (Reeves, 2000b). Both studies included multiple outcomes and it is not possible to determine the clinical significance of the reported improvements. For example, in the study of osteoarthritis of the knees, there were improvements in the non-pain outcomes (such as, swelling, buckling) compared to the placebo effect, while there was no significant improvement in the pain outcomes. In the study of osteoarthritis of the thumb and finger, the treatment group reported improvements in flexion but not pain.

The use of prolotherapy was evaluated in a prospective, uncontrolled study of adults with at least 3 months of symptomatic moderate to severe knee osteoarthritis (Rabago, 2012a). The primary objective of the study was to determine whether prolotherapy improved pain, stiffness, and function when compared to baseline status with 1-year follow-up. Participants received extra-articular injections of 15% dextrose and intra-articular prolotherapy injections of 25% dextrose at 1, 5, and 9 weeks, with “as-needed” treatments at weeks 13 and 17. The primary outcome measure was the validated Western Ontario McMaster University Osteoarthritis Index (WOMAC). Secondary outcome measure was the validated Knee Pain Scale (KPS). A total of 36 participants received an average of 4.3 prolotherapy injection sessions over a 17-week treatment period and reported progressively improved scores during the 52-week study on WOMAC and KPS measures. Participants reported overall WOMAC score improvement 4 weeks after the first injection session (17.2%, 7.6 ± 2.4 points), and continued to improve through the 52-week follow-up (36.1%, 15.9 ± 2.5 points; p<0.001). KPS scores improved in both injected (p<0.001) and uninjected knees (p<0.05). Female gender, age 46-65 years old, and body mass index of 25 kg/m2 or less were associated with greater improvement on the WOMAC index. Limitations of this study include the lack of a randomized control group and the small number of study participants.

Rabago and colleagues (2013b) evaluated the efficacy of prolotherapy in adults with at least 3 months of painful knee osteoarthritis in a study supported by the National Center for Complementary and Alternative Medicine (NCCAM). A total of 90 participants were randomized to blinded injections (3 to 5 treatments with dextrose prolotherapy or saline) or at-home exercise. The study measures were limited to subjective responses to treatment, pain, stiffness and functional limitations. All 3 groups showed improvements on the composite WOMAC, with significantly greater improvement in the prolotherapy group (15.3 points) compared to saline and exercise groups (7.6 and 8.2 points, respectively). At 52 weeks, 50% of participants in the prolotherapy group achieved the minimum clinically important difference (MCID) of a 12-point change in WOMAC, compared to 30% of saline-treated participants and 24% of exercise participants. Knee pain scores also improved in the prolotherapy group. Limitations of this study include the relatively small sample size which resulted in an inability to detect uncommon adverse events such as intolerance to medication or rare injection-related sequelae, lack of participants with very severe baseline WOMAC scores, and indirect assessment of participant satisfaction that was subject to bias.

Rabago and colleagues (2015) reported the long-term results of prolotherapy-treated individuals with knee osteoarthritis who participated in a randomized controlled trial (Rabago, 2013b) and two uncontrolled open-label follow-up studies. The prolotherapy-treated study groups were comparable, having undergone similar treatment courses and showing similar improvements in WOMAC score at 52 weeks (15.3, 12.4, 15.9 points, respectively). At the 2.5-year follow-up (range, 1.5-3.5 years), 65 participants who agreed to telephonic evaluation of outcomes reported a mean 20.9-point improvement in the WOMAC score. Limitations of this study include a risk of bias due to the open-label design and the relatively high proportion (10%) of prolotherapy-treated participants who declined to participate in the follow-up telephonic interviews.

Jahangiri and colleagues (2014) reported results of a double-blind randomized trial that compared prolotherapy to local injection of corticosteroid for the treatment of osteoarthritis in the first carpometacarpal joint. A total of 60 participants (60 hands) were randomized to three monthly prolotherapy injections or two monthly saline injections plus a corticosteroid injection in the third month. The groups were comparable at baseline, with a visual analog scale (VAS) score for pain on pressure of 6.7 in the prolotherapy group and 6.4 in the corticosteroid group. At the 6-month follow-up, pain had decreased more in the prolotherapy group compared with the corticosteroid-treated group (p<0.001). Pain on movement and hand function also improved to a greater extent in the prolotherapy group. Additional study is required to evaluate the long-term efficacy and adverse effects of repeat prolotherapy injections for the treatment of first carpometacarpal joint osteoarthritis.

Hung and colleagues (2016) performed a systematic review and meta-analysis of the literature comparing the effectiveness of dextrose prolotherapy versus control injections and exercise in the management of osteoarthritis pain. A total of 326 participants from one single-arm study (Rubago, 2012) and five randomized controlled trials (including Jahangiri, 2014; Reeves, 2000a; Reeves, 200b; and Rubago, 2013) were included in the analysis. The main outcome was determined by the severity of pain 6 months after the initial injection, derived from the VAS or knee pain scale score during movement/walking associated with the participants’ function. If pain score with movement/ walking was not available in the trial, the investigators used the pain subscale from WOMAC index as the substitute. The effectiveness of therapy was measured using a standardized mean difference between the baseline condition and status after treatment in the treatment arm using dextrose prolotherapy. For the treatment arm using dextrose prolotherapy, the effect sizes compared with baseline were 0.65 (95% confidence interval [CI], 0.14-1.17), 0.84 (95% CI, 0.40-1.27), 0.85 (95% CI, 0.60-1.10), and 0.87 (95% CI, 0.53-1.21) after the first, second, third, and fourth or more injections, respectively. Dextrose prolotherapy had a superior effect to local anesthesia (effect size, 0.38; 95% CI, 0.07-0.70) and an insignificant advantage over corticosteroids (effect size, 0.31; 95% CI, -0.18 to 0.80). There was no difference in the effect sizes regarding the use of dextrose prolotherapy compared with control injection between knee and hand joints. Limitations of this study include the small number of trials eligible for meta-analysis and heterogeneity in the subject populations, injection protocols, comparative regimens, and outcome assessment. An analysis of effect sizes of functional improvements was not performed as the data were not available in each retrieved trial. Finally, the interpretation of the effect of dextrose injection compared with corticosteroid injection was derived from only a single study.

The American Academy of Orthopaedic Surgeons (AAOS, 2017) evidenced-based clinical practice guideline on the management of osteoarthritis of the hip reviewed recent studies on the use of prolotherapy, and finding no statistical significance favoring treatment, concluded that “…randomized placebo control trials may be warranted” to establish prolotherapy’s role in clinical treatment.

Tendinopathies of the Upper and Lower Limbs

Lateral Epicondylosis

A 2009 systematic review evaluating injection therapies for lateral epicondylosis (tennis elbow) included two randomized controlled trials and one prospective case series on prolotherapy (Rabago, 2009). 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 is not available in the peer-reviewed medical literature. The second randomized, double-blind, placebo-controlled trial involved 20 individuals who had elbow pain for at least 6 months and failure of conservative therapy (that is, rest, physical therapy, nonsteroidal anti-inflammatory drugs, and two corticosteroid injections) to three treatments (over 8 weeks) of prolotherapy or saline injection. Compared to the control group, prolotherapy subjects reported improved pain scores but there was no difference in grip strength between the two groups. The authors reported that clinical improvement in prolotherapy group subjects was maintained at 52 weeks, however, additional research with a larger study population is needed (Scarpone, 2008).

Rabago and colleagues (2013a) conducted a three-arm randomized controlled trial of 26 adults (32 elbows) with chronic lateral epicondylosis for 3 months or longer who were randomized to ultrasound-guided prolotherapy with dextrose solution, ultrasound-guided prolotherapy with dextrose-morrhuate sodium solution, or watchful waiting. The primary outcome was the Patient-Rated Tennis Elbow Evaluation (100 points) at 4, 8, and 16 weeks (all groups) and at 32 weeks (prolotherapy groups). The participants receiving prolotherapy with dextrose and prolotherapy with dextrose-morrhuate reported improved Patient-Rated Tennis Elbow Evaluation composite and subscale scores at 4, 8, and/or 16 weeks compared with those in the wait-and-see group (p<0.05). At 16 weeks, when compared with baseline, the prolotherapy with dextrose and prolotherapy with dextrose-morrhuate groups reported improved composite Patient-Rated Tennis Elbow Evaluation scores by a mean of 18.7 (9.6; 41.1%) and 17.5 (11.6; 53.5%) points, respectively. The grip strength of the participants receiving prolotherapy with dextrose exceeded that of the prolotherapy with dextrose-morrhuate and the watchful waiting group at 8 and 16 weeks (p<0.05). Limitations in drawing conclusions from this pilot study include the small number of participants and the lack of blinding.

Krogh and colleagues (2012) performed a systematic review and meta-analysis of the available randomized trials, concluding there was “a paucity of evidence from unbiased trials on which to base treatment recommendations regarding injection therapies for the treatment of lateral epicondylitis.” A systematic review by Sims and colleagues (2014) confirmed this conclusion, stating that lateral epicondylitis is a condition that is usually self-limited, and resolves over a 12- to 18-month period without treatment.

Rotator Cuff Tendinopathy

Seven and colleagues (2017) studied the use of dextrose prolotherapy to reduce pain and improve shoulder function in the treatment of chronic refractory rotator cuff lesions. A total of 120 individuals with symptoms persisting for longer than 6 months were randomly assigned to receive either dextrose prolotherapy injection (n=60) or an exercise rehabilitation protocol (control group; n=60) for 3 sessions weekly for 12 weeks. Both groups were instructed to carry out a home exercise program. Clinical assessment of shoulder function was performed using a VAS score for pain, Shoulder Pain and Disability Index (SPADI), Western Ontario Rotator Cuff (WORC) Index, patient satisfaction, and shoulder range of motion. Participants were examined at baseline, weeks 3, 6, and 12, and last follow-up (minimum of one year). A total of 101 participants (n=44 control group; n=57 in the prolotherapy group) completed all study protocols and were included in the final analysis. Using a within-group comparison, both groups achieved significant improvements over baseline, as measured by the VAS, SPADI, and WORC index scores, and shoulder range of motion (p<0.001). Using between-group comparison, significant differences were found in the VAS scores between the 2 groups at 3, 6 and 12 weeks, and at the final follow-up after treatment (p<0.001). Additionally, significant differences were found in the SPADIs and WORC indices at weeks 6 and 12 and last follow-up. Significant differences were found in shoulder abduction and flexion at week 12 and last follow-up, and in internal rotation at last follow-up. However, no significant difference was found in external rotation at any follow-up period. Patient satisfaction was reported as “excellent or good” in the prolotherapy group (n=53; 92.9%) and control group (n=25; 56.8%), respectively. Two participants in the prolotherapy group (reporting poor results) and 6 participants in the control group (reporting fair to poor results) elected to undergo surgical intervention. Limitations of this study include the small sample size, lack of placebo control, and relatively short follow-up.

Bertrand and colleagues (2016) compared the effect of dextrose prolotherapy on pain levels and degenerative changes in painful rotator cuff tendinopathy. In this blinded, randomized controlled trial, 72 participants who received three monthly injections of 0.1% lidocaine with dextrose prolotherapy (entheses dextrose [Enth-Dex group]) or one of two control injections (entheses saline injection without dextrose [Enth-Saline group] or superficial saline injection [Superfic-Saline group]) were included in the 9-month follow-up data. All participants received concurrent physical therapy. The primary outcome measure was achieving an improvement in maximal current shoulder pain ≥ 2.8 (twice the minimal clinically important difference for VAS pain score). At 9 months, the Enth-Dex group maintained a 2.9-point improvement in pain in comparison with 1.8 points for the Enth-Saline group and 1.3 points for the Superfic-Saline group. The percentage of participants reaching and maintaining a clinically significant improvement of ≥ 2.8 in pain was significantly different between groups (p=0.046). The use of prolotherapy in the Enth-Dex group reported a significant improvement compared to the Superfic-Saline group (16 [59%] vs. 7 [27%]; p=0.017); however, the difference between the Enth-Dex group and the Enth-Saline group did not reach clinical significance (16 [59%] vs. 7 [37%]; p=0.088). The Ultrasound Shoulder Pathology Rating Scale was not different between the groups (p=0.734). Limitations of this study include the concurrent use of active physical therapy which may have accounted for much of the treatment benefit at short-term follow-up and lack of data to confirm improvement in physical function.

Lee and colleagues (2015) conducted a retrospective case study of individuals with nontraumatic refractory rotator cuff disease who were unresponsive to 3 months of aggressive conservative treatment. Participants in the prolotherapy treatment group (n=63) received an average number of 4.8 (± 1.3) injections of 16.5% dextrose 10-ml solution compared to no injections in the conservative treatment group (n=63). Outcome measurements analyzed over 1 year included the average shoulder pain level (VAS score) for the prior week, SPADI score, isometric strength of the shoulder abductor, active range of motion (AROM) of the shoulder, maximal tear size on ultrasonography, and number of analgesic ingestions per day. Compared to the control group, the prolotherapy treatment group showed significant improvement in all outcome measurements. No adverse events were reported. Limitations of this study include its retrospective design and lack of randomization to a sham treatment group. Prospective, double-blind randomized controlled trials are needed to confirm the clinical efficacy of prolotherapy treatment for individuals with refractory rotator cuff disease.

Achilles Tendonitis

Yelland and colleagues (2011) reported a multicenter randomized trial of prolotherapy or exercises for Achilles tendonitis in 43 individuals. While the percentage of individuals achieving full recovery was 53% for exercise alone, 71% for prolotherapy alone, and 64% for the combined treatment group, these differences were not significant. Although the authors concluded that prolotherapy may be a cost-effective method to speed recovery in individuals with Achilles tendonitis, this study is limited by small number of subjects per group, unequal duration of pain in the treatment groups at baseline, and minimal differences in the number of individuals showing recovery. Additional randomized trials are needed to replicate and extend these findings.

Gross and colleagues (2013) conducted a systematic review of clinical outcomes following injectable therapy of noninsertional Achilles tendinosis. The nine clinical studies that met the inclusion criteria at the final follow-up consisted of randomized controlled trials and cohort studies with a comparative control group (n=312 Achilles tendons). Interventions included platelet-rich plasma (n=54), autologous blood injection (n=40), sclerosing agents (n=72), protease inhibitors (n=26), hemodialysate (n=60), corticosteroids (n=52), and prolotherapy (n=20). Yelland and colleagues (2011) was the only prolotherapy study included in the review. The authors concluded that the available literature evaluating injectable treatments for noninsertional Achilles tendinosis has variable results with conflicting methodologies and inconclusive evidence concerning indications for treatment and the mechanism of their effects on chronically degenerated tendons.

Sanderson and Bryant (2015) conducted a systematic review of the literature to determine the clinical effectiveness and safety of prolotherapy injections for treatment of lower limb tendinopathy and fasciopathy. The analysis included prospective randomised and non-randomised trials, cohort studies, case-series, cross-sectional studies and controlled trials published between January 1960 and September 2014 with results that reported the effectiveness of one or more prolotherapy injections for tendinopathy or fasciopathy at or below the superior aspect of the tibia/fibula. A total of 203 studies were identified, of which 8 studies met the inclusion criteria. Studies were then grouped according to tendinopathy or fasciopathy (that is, Achilles tendinopathy, plantar fasciopathy and Osgood-Schlatter disease). The methodological quality of the eight studies was identified as “generally poor” in regards to allocation concealment, intention-to-treat analysis and blinding procedures. No adverse events following prolotherapy injections were reported in any study. The analysis found limited evidence that prolotherapy injections are a safe and effective treatment for Achilles tendinopathy, plantar fasciopathy and Osgood-Schlatter disease. Larger, methodologically-sound randomised controlled trials are needed to determine if prolotherapy injections can improve health outcomes for individuals with lower limb tendinopathy and fasciopathy.

Other Musculoskeletal and Pain-Related Conditions

Reeves and Hassanein (2003) reported on a study of dextrose prolotherapy for anterior cruciate ligament (ACL) laxity. Of 16 evaluable individuals, statistically significant improvements were found at 6, 12, and 36 months in ACL laxity, pain, swelling, and range of motion. However, this small, non-randomized trial, without placebo-control, is limited in determining if the extent of the improvements with prolotherapy exceeds those associated with a placebo.

Choi and colleagues (2011) evaluated the most current evidence in a systematic review of treatment options for athletes with osteitis pubis and osteomyelitis pubis, attempting to determine which options provide optimal pain relief with rapid return to sport and prevention of symptom reoccurrence. Treatment options included either conservative measures/physical therapy, local injection with corticosteroids and/or local anesthetic, dextrose prolotherapy, surgery or antibiotic therapy. There were no randomized controlled trials available for review. Only one case series described the use of dextrose prolotherapy as a treatment modality. The authors concluded that the evidence was weak in all case reports/case series and suggested further study is necessary to compare the different treatment options and determine which modality provides the fastest return to sport.

In a small randomized controlled trial (n=48), Kim and colleagues (2010) evaluated the efficacy and long-term effectiveness of intra-articular prolotherapy compared with intra-articular steroid injection in relieving sacroiliac joint pain. Participants experienced sacroiliac joint pain (confirmed by greater than or equal to 50% improvement in response to local anesthetic block) lasting 3 months or longer and failed medical treatment. The treatment involved intra-articular dextrose water prolotherapy or triamcinolone acetonide injection using fluoroscopic guidance, with a biweekly schedule and maximum of 3 injections. Pain and disability scores were assessed at baseline, in 2 weeks, and monthly after completion of treatment. The pain and disability scores were significantly improved from baseline in both groups at the 2-week follow-up, with no significant difference between them. The cumulative incidence of ≥ 50% pain relief at 15 months was 58.7% (95% CI, 37.9%-79.5%) in the prolotherapy group and 10.2% (95% CI, 6.7%-27.1%) in the steroid group, as determined by Kaplan-Meier analysis; there was a statistically significant difference between the groups (log-rank, p<0.005). The authors concluded that intra-articular prolotherapy provided significant relief of sacroiliac joint pain, and its effects lasted longer than those of steroid injections. However, further studies are needed to confirm the safety of the procedure and to validate an appropriate injection protocol.


At this time the scientific evidence does not permit conclusions concerning the effect of prolotherapy on net health outcomes for chronic neck or back pain, tendinopathies of the upper or lower limbs, osteoarthritic pain, or other musculoskeletal pain and related conditions. Prolotherapy injections have not been proven to be more effective than placebo injections. Additionally, treatment was frequently combined with other therapeutic modalities including exercise, spinal manipulation and various pharmaceutical solutions. Heterogeneity among studies, small populations, short-term outcomes, lack of control groups, poor study design, and the use of other treatment modalities leads to weak or inconsistent conclusions regarding improvement in health outcomes as a result of prolotherapy injections.


Prolotherapy, also known as joint sclerotherapy or reconstructive ligament therapy, has been used to treat chronic neck and back pain, musculoskeletal pain, and ligamentous instability. The procedure consists of a series of injections to stimulate tissue repair or growth by prompting release of growth factors, such as cytokines, or increasing the effectiveness of existing circulating growth factors. Proliferative or sclerosing agents used with prolotherapy have included dextrose as a single agent or combinations of dextrose, glycerine and phenol, hypertonic glucose, psyllium seed oil, sodium morrhuate (a cod liver oil derivative), or zinc sulfate. These agents are generally injected into facet joint capsule, fascia, ligament, or a combination of these sites. Prolotherapy may involve a single injection or a series of injections, often diluted with local anesthetic agents such as lidocaine or Marcaine™ (Hospira, Inc., Lake Forest, IL). Sarapin® (High Chemical Company, Levittown, PA), another agent thought to have anesthetic properties, is a derivative of the Sarraceniaceae plant and has been used in combination with sclerosing agents in prolotherapy.


Ligament: A band of fibrous tissue connecting bones or cartilages, serving to support and strengthen joints.

Prolotherapy: A procedure proposed to strengthen lax ligaments or to relieve pain by injecting chemical agents directly into torn or stretched ligaments.

Sclerosis: A thickening or hardening of a body part from excessive formation of fibrous tissue.


The following codes for treatments and procedures applicable to this document are included below for informational purposes. Inclusion or exclusion of a procedure, diagnosis or device code(s) does not constitute or imply member coverage or provider reimbursement policy. Please refer to the member's contract benefits in effect at the time of service to determine coverage or non-coverage of these services as it applies to an individual member.

When services are Investigational and Not Medically Necessary:
For the code listed below for all indications, or when the code describes a procedure indicated in the Position Statement section as investigational and not medically necessary:







ICD-10 Diagnosis



All diagnoses


Peer Reviewed Publications:

  1. Bertrand H, Reeves KD, Bennett CJ, et al. Dextrose prolotherapy versus control injections in painful rotator cuff tendinopathy. Arch Phys Med Rehabil. 2016; 97(1):17-25.
  2. Choi H, McCartney M, Best TM. Treatment of osteitis pubis and osteomyelitis of the pubic symphysis in athletes: a systematic review. Br J Sports Med. 2011; 45(1):57-64.
  3. Dagenais S, Haldeman S, Wooley JR. Intraligamentous injection of sclerosing solutions (prolotherapy) for spinal pain: a critical review of the literature. Spine J. 2005; 5(3):310-328.
  4. Dagenais S, Mayer J, Haldeman S, et al. Evidence-informed management of chronic low back pain with prolotherapy. Spine J. 2008; 8(1):203-212.
  5. Dechow E, Davies RK, Carr AJ, Thompson PW. A randomized, double-blind, placebo-controlled trial of sclerosing injections in patients with chronic low back pain. Rheumatology (Oxford). 1999; 38(12):1255-1259.
  6. Gross CE, Hsu AR, Chahal J, Holmes GB Jr. Injectable treatments for noninsertional Achilles tendinosis: a systematic review. Foot Ankle Int. 2013; 34(5):619-628.
  7. Hung CY, Hsiao MY, Chang KV, et al. Comparative effectiveness of dextrose prolotherapy versus control injections and exercise in the management of osteoarthritis pain: a systematic review and meta-analysis. J Pain Res. 2016; 9:847-857.
  8. Jahangiri A, Moghaddam FR, Najafi S. Hypertonic dextrose versus corticosteroid local injection for the treatment of osteoarthritis in the first carpometacarpal joint: a double-blind randomized clinical trial. J Orthop Sci. 2014; 19(5):737-743.
  9. Kim SR, Stitik TP, Foye PM, et al. Critical review of prolotherapy for osteoarthritis, low back pain, and other musculoskeletal conditions: a physiatric perspective. Am J Phys Med Rehabil. 2004; 83(5):379-389.
  10. 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):1285-1290.
  11. Krogh TP, Bartels EM, Ellingsen T, et al. Comparative effectiveness of injection therapies in lateral epicondylitis: a systematic review and network meta-analysis of randomized controlled trials. Am J Sports Med. 2013; 41(6):1435-1446.
  12. Lee DH, Kwack KS, Rah UW, Yoon SH. Prolotherapy for refractory rotator cuff disease: retrospective case-control study of 1-year follow-up. Arch Phys Med Rehabil. 2015; 96(11):2027-2032.
  13. Rabago D, Best TM, Beamsley M, Patterson J. A systematic review of prolotherapy for chronic musculoskeletal pain. Clin J Sport Med. 2005; 15(5):376-380.
  14. 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; 43(7):471-481.
  15. Rabago D, Lee KS, Ryan M, et al. Hypertonic dextrose and morrhuate sodium injections (prolotherapy) for lateral epicondylosis (tennis elbow): results of a single-blind, pilot-level, randomized controlled trial. Am J Phys Med Rehabil. 2013a; 92(7):587-596.
  16. Rabago D, Mundt M, Zgierska A, et al. Hypertonic dextrose injection (prolotherapy) for knee osteoarthritis: long term outcomes. Complement Ther Med. 2015; 23(3):388-395.
  17. Rabago D, Patterson JJ, Mundt M, et al. Dextrose prolotherapy for knee osteoarthritis: a randomized controlled trial. Ann Fam Med. 2013b; 11(3):229-237.
  18. Rabago D, Zgierska A, Fortney L, et al. Hypertonic dextrose injections (prolotherapy) for knee osteoarthritis: results of a single-arm uncontrolled study with 1-year follow-up. J Altern Complement Med. 2012; 18(4):408-414.
  19. Reeves KD, Hassanein KM. Long-term effects of dextrose prolotherapy for anterior cruciate ligament laxity. Altern Ther Health Med. 2003; 9(3):58-62.
  20. Reeves KD, Hassanein KM. Randomized prospective double-blind placebo-controlled study of dextrose prolotherapy for knee osteoarthritis with or without ACL laxity. Altern Ther Health Med. 2000a; 6(2):68-74, 77-80.
  21. Reeves KD, Hassanein KM. 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. 2000b; 6(4):311-320.
  22. Sanderson LM, Bryant A. Effectiveness and safety of prolotherapy injections for management of lower limb tendinopathy and fasciopathy: a systematic review. J Foot Ankle Res. 2015; 8:57. Erratum in: J Foot Ankle Res. 2015; 8:60.
  23. 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):248-254.
  24. Seven MM, Ersen O, Akpancar S, et al. Effectiveness of prolotherapy in the treatment of chronic rotator cuff lesions. Orthop Traumatol Surg Res. 2017; 103(3):427-433.
  25. Sims SE, Miller K, Elfar JC, Hammert WC. Non-surgical treatment of lateral epicondylitis: a systematic review of randomized controlled trials. Hand (NY). 2014; 9(4):419-446.
  26. Watson JD, Shay BL. Treatment of chronic low-back pain: a 1-year or greater follow-up. J Altern Complement Med. 2010; 16(9):951-958.
  27. Wilkinson HA. Injection therapy for enthesopathies causing axial spine pain and the "failed back syndrome": a single blinded, randomized and cross-over study. Pain Physician. 2005; 8(2):167-173.
  28. Yelland MJ, Del Mar C, Pirozzo S, Schoene ML. Prolotherapy injections for chronic low back pain: a systematic review. Spine (Phila Pa 1976). 2004a; 29(19):2126-2133.
  29. Yelland MJ, Glasziou PP, Bogduk N, et al. Prolotherapy injections, saline injections, and exercises for chronic low-back pain: a randomized trial. Spine (Phila Pa 1976). 2004b; 29(1):9-16; discussion 16.
  30. 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):421-428.

Government Agency, Medical Society, and Other Authoritative Publications:

  1. American Academy of Orthopaedic Surgeons (AAOS). Management of osteoarthritis of the hip evidence-based clinical practice guideline. March 13, 2017. Available at: Accessed on January 23, 2018.
  2. Centers for Medicare and Medicaid Services (CMS). National Coverage Determination: Prolotherapy, joint sclerotherapy, and ligamentous injections with sclerosing agent. NCD #150.7. Effective September 27, 1999. Available at: Accessed on January 23, 2018.
  3. 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 (Phila Pa 1976). 2009; 34(10):1078-1093.
  4. U.S. National Institutes of Health (NIH). Clinical trials: prolotherapy. Available at: Accessed on January 23, 2018.
  5. Yelland MJ, Mar C, Pirozzo S, et al. Prolotherapy injections for chronic low-back pain. Cochrane Database Syst Rev. 2004c;(2):CD004059.


Document History






Medical Policy & Technology Assessment Committee (MPTAC) review. The document header wording updated from “Current Effective Date” to “Publish Date.” Updated Rationale and References sections.



MPTAC review. Updated Rationale and References sections.



MPTAC review. Updated Rationale and References sections. Removed ICD-9 codes from Coding section.



MPTAC review. Updated Description, Rationale, and References sections.



MPTAC review. Updated Description, Rationale and Reference sections.



MPTAC review. Updated Description, Rationale, Background, Definitions, References, and Index.



MPTAC review. Updated Rationale and References.



MPTAC review. Updated Description, Rationale and References.



MPTAC review. Revised document title to Prolotherapy for Joint and Ligamentous Conditions. Clarified Position Statement. Updated Description, Rationale, Background, and References.



MPTAC review. References updated.



MPTAC review. Sarapin® moved from Description to Background. Rationale and References updated.



The phrase "investigational/not medically necessary" was clarified to read "investigational and not medically necessary." This change was approved at the November 29, 2007 MPTAC meeting.



MPTAC review. Rationale and References updated. 



Added Sarapin® to the Description.



MPTAC review. References updated. 



Added reference for Centers for Medicare and Medicaid Services (CMS) – National Coverage Determination (NCD).



MPTAC review. Revision based on Pre-merger Anthem and Pre-merger WellPoint Harmonization.

Pre-Merger Organizations

Last Review Date

Document  Number


Anthem, Inc.




Prolotherapy/Sclerotherapy for Joint and Ligamentous Injections

WellPoint Health Networks, Inc.