Blue Cross of Idaho Logo

Express Sign-on

Thank you for registering with Blue Cross of Idaho

If you are an Individual or Family Member, please register here.

If you are a Medicare Advantage or Medicare Supplement member, please register here.

MP 2.01.31 Intra-articular Hyaluronan Injections for Osteoarthritis

Medical Policy    
Original Policy Date
Last Review Status/Date
Local policy reviewed/10:2014
  Return to Medical Policy Index


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. 


Knee OA is common, costly, and a cause of substantial disability. Among U.S. adults, the most common causes of disability are arthritis and rheumatic disorders. Currently, no curative therapy is available for OA, and thus the overall goals of management are to reduce pain, disability, and the need for surgery.

IAHA has been proposed as a means of restoring the normal viscoelasticity of the synovial fluid in patients with OA and improving pain and function. This treatment may also be called viscosupplementation. HA is a naturally occurring macromolecule that is a major component of  synovial fluid and is thought to contribute to its viscoelastic properties. Chemical crosslinking of hyaluronan increases its molecular weight; cross-linked hyaluronans are referred to as hylans. In OA, the overall length of HA chains present in cartilage and the HA concentration in the synovial fluid are decreased.

Regulatory Status

Seven preparations of intra-articular (IA) hyaluronan have been approved by FDA as an alternative to nonsteroidal anti-inflammatory drug therapy in the treatment of OA of the knee (Synvisc® and Synvisc-One®, Genzyme; Gel-One®, Zimmer; Hyalgan®, Fidia; Supartz®, Smith and Nephew; OrthoVisc®, Anika; and Euflexxa®, previously named Nuflexxa, Savient). All products are manufactured from rooster combs except for Euflexxa and Orthovisc, which are produced from bacterial fermentation. Also, Synvisc undergoes additional chemical crosslinking to create hylans with increased molecular weight (6000 kDa) compared with Hyalgan (500-730 kDa) and Supartz (620-1170 kDa). The differing molecular weights of the products lead to different half-lives; the half-life of Hyalgan or Supartz is estimated at 24 hours, while the half-life of Synvisc may range up to several days.

IAHA is “indicated for the treatment of pain in osteoarthritis of the knee in patients who have failed to respond adequately to conservative nonpharmacologic therapy, and to simple analgesics, e.g., acetaminophen.” The product inserts further indicate that Synvisc® and Euflexxa® should be injected intra-articularly into the knee joint once per week for a total of 3 injections over a 2- to 3-week period. In contrast, 5 weekly injections are recommended for the Hyalgan® and Supartz® products, and 3 to 4 weekly injections are recommended for OrthoVisc®. In February 2009, FDA approved the use of singledose hylan G-F 20 (Synvisc-One™) for the treatment of OA of the knee. In 2011, FDA approved the use of the single-dose cross-linked hyaluronate Gel-One® (also known as Gel-200) for the treatment of OA of the knee.

In 2000, FDA approved removal of a precautionary statement from the package inserts for Hyalgan and Synvisc that stated that the safety and efficacy of repeat courses have not been established.

FDA has not approved intra-articular hyaluronan for joints other than the knee.

FDA product code: MOZ


Intra-articular hyaluronan injections may be considered medically necessary for treatment of painful osteoarthritis of the knee in patients who have insufficient pain relief from conservative nonpharmacologic therapy, simple analgesics, and intra-articular corticosteroid injections (unless contra-indicated).

Repeated courses of intra-articular hyaluronan injections of the knee may be considered medically necessary under the following conditions:

  • Significant pain relief achieved with the prior course of injections; and
  • At least 6 months have passed since completion of the prior course.

The use of intra-articular hyaluronan in the knee when the above criteria are not met, and in joints other than the knee, is considered investigational.

Policy Guidelines

Appropriate candidates for hyaluronan injections are those who have failed conservative therapy with nonsteroidal anti-inflammatory drugs (NSAIDs) or who have contraindications to NSAID therapy. Plans may also require candidates for hyaluronan injections to have failed intra-articular injections of corticosteroids.

A course of hyaluronan injections is defined according to labeled indications for each product; one formulation involves a single injection, others use multiple injections. For example, Synvisc-One® is a single 6-mL injection treatment regimen. For a single course of treatment, the single injection formulation should not be followed with subsequent doses of the multiple-injection formulations.

When determining the timing of repeated courses, the prior course is assumed to have been completed at the date of the last injection of the series of injections.

The procedure may be billed using a combination of CPT codes to describe the procedure and J codes to describe the hyaluronic acid product.

CPT code

20610: Arthrocentesis, aspiration or injection; major joint or bursa

The initial office visit to initiate hyaluronan therapy may be billed using an evaluation and management CPT code; however, the use of both CPT code 20610 and an evaluation and management CPT code during subsequent visits for the sole purpose of hyaluronan injections is not routinely warranted.

The following HCPCS codes are specific to the various hyaluronan products:

J7321: Hyaluronan or derivative, Hyalgan or Supartz, for intra-articular injection, per dose

J7323: Hyaluronan or derivative, Euflexxa, for intra-articular injection, per dose

J7324: Hyaluronan or derivative, Orthovisc, for intra-articular injection, per dose

J7325: Hyaluronan or derivative, Synvisc or Synvisc-One, for intra-articular injection, 1 mg

J7326: Hyaluronan or derivative, Gel-One, for intra-articular injection, per dose 

Benefit Application
BlueCard/National Account Issues

The coverage for hyaluronan injections is typically based on coverage benefits for injectable drugs, in addition to the office visit.

State or federal mandates (e.g., FEP) may dictate that all devices approved by the U.S. Food and Drug Administration (FDA) may not be considered investigational and must be considered on the basis of medical necessity.


This policy was created in 1998 and updated regularly with searches of the MEDLINE database. The most recent literature review was performed through September 3, 2014.

Assessment of efficacy for a therapeutic intervention involves a determination of whether the technology improves health outcomes. The optimal study design for this purpose is a randomized controlled trial (RCT) that includes clinically relevant measures of health outcomes. Intermediate outcome measures, also known as surrogate outcome measures, may also be adequate if there is an established link between the intermediate outcome and true health outcomes. Nonrandomized comparative studies and uncontrolled studies can sometimes provide useful information on health outcomes, but are prone to biases such as noncomparability of treatment groups, the placebo effect, and  variable natural history of the condition. As there are a number of RCTs on intra-articular hyaluronan (IAHA) for osteoarthritis (OA), this evidence review will focus on RCTs and systematic reviews.


Systematic Reviews

This policy was originally based on a 1998 TEC Assessment on IAHA for OA,(1) and in 2004, TEC published a Special Report on IAHA for OA of the knee.(2) Overall, the 2004 review found that the evidence was still consistent with that presented in the 1998 TEC Assessment, showing a statistically significant effect in almost all studies, although the magnitude and clinical significance of the effect may be small. Similar results were obtained in Cochrane reviews in 2005 and 2006.(3,4) In 2007, the TEC Evidence-based Practice Center published a technology assessment for the Agency for Healthcare Research and Quality on the treatment of primary and secondary OA of the knee.(5) The report concluded that results from 42 trials (n=5843) generally show positive effects of viscosupplementation on pain and function scores compared with placebo for patients with primary OA of the knee. However, the evidence on viscosupplementation was accompanied by considerable uncertainty due to variable trial quality, potential publication bias, and unclear clinical significance of the changes reported. Trials of hylan G-F 20 (Synvisc, 6000 kDa), the highest molecular weight cross-linked product, generally reported better results than other trials. Similar concerns were noted in a 2012 meta-analysis of 89 trials (12,667 patients) on viscosupplementation for OA of the knee6 and a 2013 systematic review from the American Academy of Orthopaedic Surgeons (AAOS) on treatments for OA of the knee.(7)

In 2014, TEC published a systematic review of recent meta-analyses on the treatment of knee OA with IAHA.(8) Included in the assessment were 5 meta-analyses published in 2011 or later.(6,7,9-11) Two metaanalyses concluded that IAHA provides a clinically meaningful benefit; 3 concluded that the evidence did not demonstrate a clinically meaningful benefit. It was not possible from the data to determine the proportions of patients achieving clinically meaningful improvement, although the AAOS analysis determined that is was unlikely that an appreciable number of patients would benefit compared with placebo. It is also possible that these results were biased in favor of IAHA, due to unpublished trial data. When results from unpublished trials were obtained, the magnitude of effect was notably lower compared with published results. Substantial heterogeneity between trials was also evident, increasing uncertainty. The Assessment concluded that the 5 meta-analyses, sampling from a similar collection of published trials and 2 unpublished ones, highlights biases and difficulty ascertaining clinically meaningful patientlevel improvement compared with placebo. Although accumulating evidence would be expected to increase certainty about whether a clinically important treatment benefit exists, the current study results do not provide convincing evidence that net health outcomes are improved with IAHA over placebo.


Migliore et al conducted a review of 7 studies on IAHA for ankle OA, identified from the period of 2006 to 2009, that included 3 small RCTs with a total of 75 patients, and 4 case series.(13) For 2 of the RCTs, IAHA was compared with saline injection, and the results showed benefit on some outcome measures but not others. The third RCT compared IAHA with exercise therapy and reported no differences in outcomes. The authors were unable to do a meta-analysis due to the limited number of studies and study heterogeneity.

In 2012, DeGroot et al reported on an RCT of 64 patients with ankle OA that compared a single IAHA with a single intra-articular (IA) saline injection.(14) At 6 weeks and 12 weeks, there were no significant differences in improvement between treatment groups on the American Orthopaedic Foot & Ankle Society clinical rating score, the Ankle Osteoarthritis Scale score, and the patient-reported visual analog scale (VAS) for pain.


There is a very limited amount of evidence on IAHA injections in the foot. Munteanu et al reported on an RCT of a single IAHA injection in 151 patients with first metatarsophalangeal joint OA.(15) At 1-, 3-, and 6-month follow-up, there were no significant differences between the IAHA and placebo groups on the Foot  Health Status Questionnaire.


Two small RCTs that enrolled a total of 100 patients evaluated HA injections compared with steroid injections for arthritis of the thumb.(16,17) Fuchs et al(17) reported that steroid injections were superior at 2 to 3 weeks posttreatment but that IAHA was superior at 6-month follow-up. Stahl et al16 reported essentially equivalent outcomes between steroid injections and IAHA, although IAHA was superior to steroids for some aspects of fine motor function. The results of these trials are not sufficient to determine the efficacy of IAHA for thumb arthritis and are not sufficient for determining comparative efficacy with steroids.


A 2008 systematic review of 2 RCTs and 9 cohort studies concluded that viscosupplementation therapy with HA appears to be “a safe and effective method in the treatment of hip OA resistant to conventional treatment modalities.”18 In their 2012 systematic review, Colen et al identified 3 RCTs that compared IAHA with placebo, 1 that compared IAHA with IA anesthetic, and 1 that compared hyaluronans of different molecular weights.(12) These 3 trials showed a statistical effect favoring IAHA treatment. However, the effect size was small compared with saline injections, and there were not significant differences between IAHA and other conservative treatments such as steroid injections.

The largest RCT randomized 101 patients to receive either HA injections or saline.(19) There was a small reduction in pain with walking in patients treated with HA injections over the 3-month evaluation period. An industry-sponsored RCT compared a single 2.5 mL IAHA (Adant, 900 kDa, unavailable in the United States) with saline injection for treatment of hip OA in 85 patients.(20) At 3 months, there were no significant differences between groups in any outcome measure. The number of patients who experienced mild to moderate treatment-related adverse events (injection-site pain, pain flare, hematoma, pruritus) did not differ between groups. Atchia et al reported on an RCT of 77 patients with hip OA who were potential candidates for total hip replacement.(21) In this study, patients were randomized to receive standard care or an injection of saline, HA or methylprednisolone and followed for 8 weeks. Significant improvement was only seen in the steroid group in the numerical rating scale for worst pain, and the Western Ontario and McMaster Osteoarthritis Index for pain and function. No improvements were reported in the IAHA group.

In an industry-sponsored, single-center, randomized, double-blind, active-controlled trial, published in 2009, 42 patients with OA of the hip were randomly assigned to receive 2 monthly injections of highmolecular weight IAHA (Hyalubrix®, unavailable in the United States) or IA mepivacaine, a local anesthetic.(22) At 3 and 6 months, there was a significant decrease in the Lequesne algofunctional index in the IAHA group compared with the mepivacaine group (5.15 vs 6.53 at 3 months; 3.94 vs 6.41 at 6 months, both respectively). The only reported adverse event was injection-site pain occurring in 1 patient in each group.


A 2010 meta-analysis of 19 blinded RCTs examined the use of viscosupplementation for chronic painful shoulder in a total of 2120 patients.(23) A variety of shoulder disorders were included, eg, adhesive capsulitis, rotator cuff tear, shoulder impingement syndrome, frozen shoulder. Sample size ranged from 20 to 660 patients, mean trial duration was 3.5 weeks, and mean Jadad score was 3.5±1.5. Ten trials (1435 patients) reported pain outcomes. The combined effect size (standardized mean difference) for categorical and continuous pain ratings favored IAHA (0.39). There was no heterogeneity and no evidence of publication bias. Because the studies included in the meta-analysis were of short duration and included a variety of shoulder diseases, they do not provide conclusive evidence of the effectiveness of IAHA in OA of the shoulder.

The largest trial is an industry-sponsored RCT of 660 patients with persistent shoulder pain due to glenohumeral joint OA, rotator cuff tear, and/or adhesive capsulitis compared 3 weekly injections versus 5 weekly injections of sodium hyaluronate (Hyalgan) versus 5 weekly injections of saline.(24) Approximately 60% of patients had OA, although most of those with OA also had rotator cuff disorders or capsulitis. Sixty-nine percent (n=456) of the patients had a follow-up visit at 26 weeks. There was no significant difference among groups in the primary outcome measure, shoulder pain with movement at 13 weeks. Analysis of predefined, stratified subgroups revealed no significant differences in reported pain at 13 weeks but a statistically significant decrease of 7.5 and 7.8 mm (on a 100-mm VAS) in reported pain in both treatment groups at 26 weeks compared with placebo among patients with OA. In those without OA, there was no significant improvement with either regimen. Of note, this appears to be an as-treated analysis of the OA subgroup data, and the difference may not be clinically important.

In 2013, Kwon et al reported a multicenter randomized double-blind placebo-controlled trial of IAHA in 300 patients with glenohumeral OA.(25) Intention-to-treat analysis found similar improvement in VAS for pain (19.88 mm for IAHA, 16.29 mm for placebo) and in the Outcome Measures in Rheumatoid Clinical Trials-Osteoarthritis Research Society International (OMERACT-OARSI) high responder rate (40.8% for IAHA, 34.9% for sham). In a subset of patients, there was a statistically significant difference in VAS of 4.0 mm on a 100-mm scale and 8.37% on the OMERACT-OARSI. However, the clinical significance of these differences is uncertain.


Data from small pilot studies, and case series have been reported using HA for arthritis of the spine and for lateral condylitis of the elbow (tennis elbow).

Section Summary

The evidence on the efficacy of IAHA for joints other than the knee is less robust. While some studies show benefit, others do not, and systematic reviews have not concluded that there is a clinically significant benefit.

Ongoing and Unpublished Clinical Trials
An online search of in September 2014 identified a number of open trials with IAHA. These include phase 3 and phase 4 trials evaluating IAHA for OA of the knee (NCT01372475, NCT01543737, NCT01557868, and NCT01335321), and a pivotal multicenter trial of Hylan G-F 20 for OA of the hip (NCT01618708).

Clinical Input Received From Physician Specialty Societies and Academic Medical Centers
While the various physician specialty societies and academic medical centers may collaborate with and make recommendations during this process through the provision of appropriate reviewers, input received does not represent an endorsement or position statement by the physician specialty societies or academic medical centers, unless otherwise noted.

In response to requests, input was received from 3 physician specialty societies and 5 academic medical centers (6 reviewers) while this policy was under review in 2011. Most reviewers agreed that IAHA of the knee was medically necessary. In addition, those providing input supported an interval of 6 months for repeat injections. In response to a question about total number of treatment courses, there was no consensus.

Summary of Evidence

Intra-articular injection of hyaluronan into osteoarthritic joints is thought to replace hyaluronan, restore the viscoelastic properties of the synovial fluid, and improve pain and function. The largest amount of evidence is on treatment of osteoarthritis (OA) of the knee. Individual trials show inconsistent results in pain and functional outcomes for intra-articular injection of hyaluronan (IAHA) compared with placebo or active control. Meta-analyses of randomized controlled trials (RCTs) show improvements in pain and function that are statistically significant, but have not been demonstrated to be clinically significant in an appreciable number of patients.

IAHA continues to be investigated for off-label uses in other joints. Current evidence on these off-label uses is limited, consisting of small RCTs and case series. Some RCTs on IAHA injections for OA of the ankle, foot, hand and shoulder have shown treatment benefits; however, these studies are not consistent in reporting improvements that are significantly greater than placebo and/or control treatments. RCTs on IAHA injections for OA of the hip have also been inconsistent, with some RCTs reporting improvements in outcomes with IAHA hip injections and others reporting no improvement. Currently, given the limited and inconsistent available data, and the low likelihood that IAHA for joints other than the knee are more effective than IAHA for the knee, these uses are also considered not medically necessary.

Practice Guidelines and Position Statements

he American Academy of Orthopaedic Surgeons’ (AAOS) 2013 guideline on treatment of OA of the knee states that they cannot recommend using HA for patients with symptomatic knee OA.(7) This is a strong recommendation, meaning that the quality of the supporting evidence is high. This recommendation was based on a meta-analysis of 3 high-strength and 11 moderate-strength studies that showed that the overall effect was less than 0.5 minimally important different units, indicating a low likelihood that an appreciable number of patients achieved clinically important benefits. AAOS states that practitioners should follow a strong recommendation unless a clear and compelling rationale for an alternative approach is present. This replaces a 2008 guideline in which a recommendation could not be made for IAHA due to inconclusive evidence.

The 2009 AAOS Clinical Practice Guideline on glenohumeral joint osteoarthritis26 includes a weak grade C recommendation that “the use of injectable viscosupplementation is an option when treating patients with glenohumeral [shoulder] osteoarthritis.” Grade C recommendations are based on poor-quality evidence. In this instance, the recommendation is based on a single case series of 30 patients with OA of the glenohumeral joint who received 3 weekly IA injections of Synvisc.(27) At 1, 3, and 6 months, clinically significant improvements were seen in pain, function, and quality-of life-measures.

The American College of Rheumatology (ACR) published updated guidelines in 2012 that addressed OA of the hand, hip, and knee.(28) A conditional recommendation was given for IAHA to treat OA of the knee. ACR recommends not using IAHA for OA of the hand. For OA of the hip, ACR explicitly makes no recommendation regarding treatment with IAHA.

The 2014 Osteoarthritis Research Society International guidelines, developed by consensus after review of existing guidelines and systematic reviews, gave an “uncertain” recommendation for the use of intraarticular injection of HA for knee OA and a recommendation of “not appropriate” for multiple-joint OA.(29)

2014 Guidelines published by the National Institute for Health and Clinical Excellence30 state intraarticular corticosteroid injections should be considered, however intra-articular hyaluronan injections for osteoarthritis should not be offered.

U.S. Preventive Services Task Force Recommendations
Use of hyaluronan injections is not a preventive service.

Medicare National Coverage
There is no national coverage determination (NCD). In the absence of an NCD, coverage decisions are left to the discretion of local Medicare carriers.


  1. Blue Cross and Blue Shield Association Technology Evaluation Center (TEC). Intra-Articular Hyaluronan Injections for Treatment of Osteoarthritis of the Knee. TEC Assessments 1998;Volume 13, Tab 17. PMID
  2. Blue Cross and Blue Shield Association Technology Evaluation Center (TEC). Special Report: intra-articular hyaluronan for osteoarthritis of the knee. TEC Assessments. 2004;Volume 19, Tab 17. PMID
  3. Bellamy N, Campbell J, Robinson V, et al. Viscosupplementation for the treatment of osteoarthritis of the knee. Cochrane Database Syst Rev. 2005(2):CD005321. PMID 15846754
  4. Bellamy N, Campbell J, Robinson V, et al. Viscosupplementation for the treatment of osteoarthritis of the knee. Cochrane Database Syst Rev. 2006(2):CD005321. PMID 16625635
  5. Samson DJ, Grant MD, Ratko TA, et al. Treatment of primary and secondary osteoarthritis of the knee. AHRQ Publication No. 07-E012. September 2007; Accessed June, 2014.
  6. Rutjes AW, Juni P, da Costa BR, et al. Viscosupplementation for osteoarthritis of the knee: a systematic review and meta-analysis. Ann Intern Med. Aug 7 2012;157(3):180-191. PMID 22868835
  7. American Academy of Orthopaedic Surgeons. Treatment of osteoarthritis of the knee. 2013; Accessed June, 2014.
  8. Blue Cross and Blue Shield Association Technology Evaluation Center (TEC). Intra-articular hyaluronic acid for osteoarthritis of the knee. TEC Assessments. 2014;in press. PMID
  9. Bannuru RR, Natov NS, Dasi UR, et al. Therapeutic trajectory following intra-articular hyaluronic acid injection in knee osteoarthritis--meta-analysis. Osteoarthritis Cartilage. Jun 2011;19(6):611-619. PMID 21443958
  10. Colen S, van den Bekerom MP, Mulier M, et al. Hyaluronic acid in the treatment of knee osteoarthritis: a systematic review and meta-analysis with emphasis on the efficacy of different products. BioDrugs. Aug 1 2012;26(4):257-268. PMID 22734561
  11. Miller LE, Block JE. US-Approved Intra-Articular Hyaluronic Acid Injections are Safe and Effective in Patients with Knee Osteoarthritis: Systematic Review and Meta-Analysis of Randomized, Saline-Controlled Trials. Clin Med Insights Arthritis Musculoskelet Disord. 2013;6:57-63. PMID 24027421
  12. Colen S, Haverkamp D, Mulier M, et al. Hyaluronic acid for the treatment of osteoarthritis in all joints except the knee: what is the current evidence? BioDrugs. Apr 1 2012;26(2):101-112. PMID 22385405
  13. Migliore A, Giovannangeli F, Bizzi E, et al. Viscosupplementation in the management of ankle osteoarthritis: a review. Arch Orthop Trauma Surg. Jan 2011;131(1):139-147. PMID 20697901
  14. Degroot H, Uzunishvili S, Weir R, et al. Intra-articular injection of hyaluronic Acid is not superior to saline solution injection for ankle arthritis: a randomized, double-blind, placebo-controlled study. J Bone Joint Surg Am. Jan 4 2012;94(1):2-8. PMID 22218376
  15. Munteanu SE, Zammit GV, Menz HB, et al. Effectiveness of intra-articular hyaluronan (Synvisc, hylan G-F 20) for the treatment of first metatarsophalangeal joint osteoarthritis: a randomised placebo-controlled trial. Ann Rheum Dis. Oct 2011;70(10):1838-1841. PMID 21791454
  16. Stahl S, Karsh-Zafrir I, Ratzon N, et al. Comparison of intraarticular injection of depot corticosteroid and hyaluronic acid for treatment of degenerative trapeziometacarpal joints. J Clin Rheumatol. Dec 2005;11(6):299-302. PMID 16371798
  17. Fuchs S, Monikes R, Wohlmeiner A, et al. Intra-articular hyaluronic acid compared with corticoid injections for the treatment of rhizarthrosis. Osteoarthritis Cartilage. Jan 2006;14(1):82-88. PMID 16242353
  18. Abate M, Pelotti P, De Amicis D, et al. Viscosupplementation with hyaluronic acid in hip osteoarthritis (a review). Ups J Med Sci. 2008;113(3):261-277. PMID 18991239
  19. Qvistgaard E, Christensen R, Torp-Pedersen S, et al. Intra-articular treatment of hip osteoarthritis: a randomized trial of hyaluronic acid, corticosteroid, and isotonic saline. Osteoarthritis Cartilage. Feb 2006;14(2):163-170. PMID 16290043
  20. Richette P, Ravaud P, Conrozier T, et al. Effect of hyaluronic acid in symptomatic hip osteoarthritis: a multicenter, randomized, placebo-controlled trial. Arthritis Rheum. Mar 2009;60(3):824-830. PMID 19248105
  21. Atchia I, Kane D, Reed MR, et al. Efficacy of a single ultrasound-guided injection for the treatment of hip osteoarthritis. Ann Rheum Dis. Jan 2011;70(1):110-116. PMID 21068096
  22. Migliore A, Massafra U, Bizzi E, et al. Comparative, double-blind, controlled study of intra-articular hyaluronic acid (Hyalubrix) injections versus local anesthetic in osteoarthritis of the hip. Arthritis Res Ther. 2009;11(6):R183. PMID 20003205
  23. Saito S, Furuya T, Kotake S. Therapeutic effects of hyaluronate injections in patients with chronic painful shoulder: a meta-analysis of randomized controlled trials. Arthritis Care Res (Hoboken). Jul 2010;62(7):1009-1018. PMID 20235211
  24. Blaine T, Moskowitz R, Udell J, et al. Treatment of persistent shoulder pain with sodium hyaluronate: a randomized, controlled trial. A multicenter study. J Bone Joint Surg Am. May 2008;90(5):970-979. PMID 18451387
  25. Kwon YW, Eisenberg G, Zuckerman JD. Sodium hyaluronate for the treatment of chronic shoulder pain associated with glenohumeral osteoarthritis: a multicenter, randomized, double-blind, placebo-controlled trial. J Shoulder Elbow Surg. Jan 16 2013;22(5):584-594. PMID 23333168
  26. American Academy of Orthopaedic Surgeons. The treatment of glenohumeral joint osteoarthritis: guideline and evidence report. 2009; Accessed June, 2014.
  27. Silverstein E, Leger R, Shea KP. The use of intra-articular hylan G-F 20 in the treatment of symptomatic osteoarthritis of the shoulder: a preliminary study. Am J Sports Med. Jun 2007;35(6):979-985. PMID 17395958
  28. Hochberg MC, Altman RD, April KT, et al. American College of Rheumatology 2012 recommendations for the use of nonpharmacologic and pharmacologic therapies in osteoarthritis of the hand, hip, and knee. Arthritis Care Res (Hoboken). Apr 2012;64(4):465-474. PMID 22563589
  29. McAlindon TE, Bannuru RR, Sullivan MC, et al. OARSI guidelines for the non-surgical management of knee osteoarthritis. Osteoarthritis Cartilage. Mar 2014;22(3):363-388. PMID 24462672
  30. National Institute for Health and Clinical Excellence (NICE). CG177 Osteoarthritis: Care and management in adults. 2008; June, 2014.




CPT  20610  Arthrocentesis, aspiration and/or injection, major joint or bursa 
ICD-9 Procedure  81.92  Injection of therapeutic substance into joint or ligament 
ICD-9 Diagnosis  715–715.9  Osteoarthrosis code range. A fifth digit of “6” in the ICD-9 code indicates osteoarthrosis of the knee 
HCPCS  J7321  Hyaluronan or derivative, Hyalgan or Supartz, for intra-articular injection, per dose
  J7322 Hyaluronan or derivative, Synvisc, for intra-articular injection, per dose
  J7323 Hyaluronan or derivative, Euflexxa, for intra-articular injection, per dose
  J7324 Hyaluronan or derivative, Orthovisc, for intra-articular injection, per dose
  J7325 Hylauronan or derivative, Synvisc or Synvosc-One, for intra-articular injection, 1mg
  J7326 Hyaluronan of knee, code range
ICD-10-CM(effective 10/1/15)  M17.0-M17.9 Osteoarthritis of knee, code range
ICD-10-PCS (effective 10/1/15) 3E0U3GC Administration, introduction, joints, percutaneous, other therapeutic substance, other substance
Type of Service  Medicine 
Place of Service  Office 

Hyaluronan Injections
Osteoarthritis, Treatment with Hyaluronan

Policy History

Date Action Reason
07/10/98 Add to Medicine section New policy
08/18/00 Replace policy Policy revised to include discussion of multiple courses of therapy, which are no longer identified as investigational
05/31/01 Replace policy Policy revised with reference to Supartz, new preparation of Hyaluronan; policy statement essentially unchanged
04/29/03 Replace policy Policy updated with literature review; policy statement unchanged
04/16/04 Replace policy Correction. Deleted the statement, “repeated courses of intra-articular hyaluronan injections are considered investigational.” from the policy statement. This revision should have been done after the last review in April 2003
07/15/04 Replace policy Added in TEC Special Report conclusions; policy statement unchanged 
06/27/05 Replace policy Literature review update for the period of April 2004 through May 2005; no new clinical trial information available that would alter the policy conclusions, therefore, the policy statement is unchanged. Added information on December 2004 FDA approval of Euflexxa and reference numbers 8 and 9 
04/25/06 Replace policy – error correction only Correction. The July 2004 history should indicate the statement, “repeated courses of intra-articular hyaluronan injections are considered investigational,” was placed back into the policy statement 
10/10/06 Local Policy Literature review update for the period of May 2005 through July 2006; noted Nuflexxa’s name was changed to Euflexxa; added reference numbers 10 through 14. Policy title changed with removal of “of the Knee.” Policy statement unchanged. HCPCS coding updated. 
01/04/08 Replace Local Policy  Added HCPCS codes, references 15-18; statement unchanged
07/09/09 Replace policy Policy updated with literature review; reference numbers 19–26 added; current policy statements modified to include use of single-dose formulation
08/12/10 Replace policy- no longer local Policy updated with literature review; reference numbers 26-36 added; policy statements unchanged
02/10/11 Replace policy Policy updated with review of clinical input, policy statements unchanged
2/09/12 Replace policy Policy updated with literature review; Rationale section extensively reordered; reference numbers 14, 19, 22-26, 35, 38 and 42 added; policy statements unchanged
4/12/12 Replace policy- correction only References 1 and 6 corrected
2/14/13 Replace policy Policy updated with literature review through January 23, 2013; Rationale section revised; references added and reordered; some references removed; policy statements unchanged
8/13/13 Local policy created policy updated to local status; steroid injection added to med nec indication
9/12/13 Local policy reviewed remains local; new literature and Guidelines from AAOS proposed service as not medically necessary. will remain local policy and medically necessary where indicated.
10/9/14 Replace policy Policy updated with literature review through September 3, 2014; references 8-11 and 29 added; existing policy statement divided into 2 separate statements. One for the knee (not medically necessary) and the second for all other joints (investigational).

Resource Center

Find a Provider Find a Pharmacy Medicare Medicare Formulary