The scope of this document encompasses the use of hyaluronan or hylan G-F 20 for the replacement or supplementation of naturally occurring intra-articular lubricants in individuals with musculoskeletal conditions in joints other than the knee, including osteoarthritis (OA) and temporomandibular joint (TMJ) disease. This therapy may also be referred to as viscosupplementation. 

Medically Necessary:

A single course of intra-articular injections of hyaluronan or hylan G-F 20 is considered medically necessary for the treatment of pain due to reducing and non-reducing disc displacement disease of TMJ disorders. A single course usually involves weekly injections (seven days apart) for three to five consecutive weeks.

Investigational and Not Medically Necessary:

Intra-articular injections of hyaluronan or hylan G-F 20 for other musculoskeletal conditions of joints other than the knee, including but not limited to osteoarthritis of the ankle, shoulder or hip, are considered investigational and not medically necessary.

Disorders of the Temporomandibular Joint

A literature search identified several published randomized controlled clinical trials that consistently reported that compared to placebo or corticosteroid injection, hyaluronan injection provided improved pain relief, improvement in range of motion and jaw function, and decreased rate of recurrence in subjects with TMJ disorders (Alpaslan, 2001; Bertolami, 1993; Bjornland, 2007; Hepguler, 2002). While the studies addressing hyaluronan injections as a treatment of TMJ dysfunction are limited in number, viscosupplementation is an accepted treatment for TMJ disorders.  

Osteoarthritis of the Hip 

Qvistgaard and colleagues (2006) reported on the results of a randomized placebo-controlled trial of hyaluronan injections in 101 individuals with osteoarthritis of the hip compared to corticosteroid or saline injection. The researchers reported that over the three month evaluation period, the participants who received hyaluronan injections reported only a small reduction in pain with walking compared to those injected with corticosteroid who reported significant pain reductions with walking.

In a systematic review for osteoarthritis of the hip (Fernández López, 2006), two independent reviewers applied a series of inclusion and exclusion criteria to the studies located in the search, and selected only those that included more than 20 participants; had a follow-up period of more than 1 week; and exclusively assessed the efficacy and/or effectiveness of hyaluronan in those with confirmed OA of the hip. A total of eight studies consisting of clinical trials and one review, met the inclusion criteria. Only two of the trials were controlled: one compared two hyaluronan products of different molecular weights; and the other compared hyaluronan injections with corticoids and a placebo. Pain relief was estimated to be around 40-50% by most studies, though the duration of this post-treatment effect was not known. The researchers concluded that based on available evidence, hyaluronan injections as a treatment of OA of the hip should be used under careful supervision by the clinician and only in those instances where other treatments have failed in hip OA. The researchers noted that methodological limitations include short follow-up periods, dissimilar ways of measuring outcomes and the absence of a control group in many of the studies.

Another systematic review (van den Bekerom, 2008) sought to identify studies relating to the use of viscosupplementation as a treatment for OA of the hip. Sixteen articles addressing the efficacy of a total of 509 participants undergoing viscosupplementation for OA of the hip were included. The products evaluated included Hylan G-F 20, Hyalgan, Ostenil, Durolane, Fermatron and Orthovisc. While the researchers concluded that viscosupplementation might have a beneficial effect in relieving pain in individuals suffering with OA of the hip, additional comparative studies are needed before it can be recommended as standard therapy in OA of the hip.

Richette and colleagues (2009) reported the findings of a multicenter, randomized, parallel-group, placebo-controlled trial which evaluated the efficacy and tolerability of a single intra-articular injection of hyaluronic acid for the treatment of OA of the hip. Eighty-five participants were randomized to either the hyaluronic acid group (n = 42) or placebo group (n = 43). At the end of three months no difference in efficacy was noted between the two groups. The findings indicated that a single intra-articular injection of hyaluronic acid was no more effective than placebo in treating the symptoms of OA of the hip. However, the value of the study results were limited by the small number of participants included in each study arm and the fact that the hyaluronan injections were administered only once versus the multiple injections typically administered for other indications.

Osteoarthritis of Other Joints

Hyaluronan injection has also been studied in other joints, including the shoulder, ankle, and thumb. Blaine and colleagues (2008) reported on the results of a multi-institutional randomized study of 660 individuals with shoulder pain related to glenohumeral osteoarthritis, rotator cuff tear or adhesive capsulitis. All participants had failed prior management with physical therapy, at least one corticosteroid injection and the administration of oral pain medications. Baseline pain levels ranged from 40 to 90 mm on a 100 mm visual analog scale. Limitation of active range of motion in at least one of several directions was also required. Participants were randomized to either a course of 3 or 5 injections of hyaluronan or placebo injection. The primary outcome was improvement in shoulder pain at 13 weeks; the secondary outcome was the maintenance of pain relief through the 26 week follow-up. A total of 456 participants completed the 26 weeks of follow-up; 20% had discontinued the study at week 26. Using an intent to treat analysis, at week 13 (the primary outcome measure), all three groups showed significant reductions in pain from baseline that were not significantly different from one another. At week 26, the 3-injection hyaluronan group did show a small but statistically significant reduction in pain compared to the placebo group. Specifically, compared to the placebo group, the difference in mean reduction from baseline was 7.2 mm on a 100 mm scale for the three-injection group. This trial did not meet its primary outcome, and the questionable clinical significance of the modest improvements noted at other time points is another limitation of this study.

Another study reported on 39 individuals with osteoarthritis of the shoulder who received injections of Hylan G-F 20 (Noel, 2010). Baseline visual analog scores ranged from 40/100 to 90/100. Each participant received one intra-articular injection of Hylan G-F 20. Participants could be scheduled for a second injection at the 1-month, 2-month, or 3-month visit. Participants were reevaluated at 7 days and 1, 2, 3, and 6 months following the injection. Thirty-three individuals received an initial injection. Sixteen individuals required a second injection. Four participants left the study due to unacceptable pain (which left 29 total participants). Visual analog score decreased from 61.2mm at baseline to 37.1mm at 3 months following an injection. In this particular study 52% of participants reported good pain relief following one injection; however the authors did state that "controlled trials are needed to confirm our results and determine optimal treatment schedule."

A literature search identified randomized controlled trials focusing on osteoarthritis of the ankle, but no trial enrolled more than 50 participants (Cohen, 2008; Karatosun, 2008; Salk, 2006; Witteveen, 2010). Similarly, randomized controlled trials comparing hyaluronan and corticosteroid injection in individuals with osteoarthritis of the thumb have reported superior results associated with the corticosteroid injection (Fuchs, 2006; Stahl, 2005).

One treatment for TMJ disorders is the injection of substances into the joint, to replace synovial fluid. Hyaluronates are one class of synovial fluid replacements. These substances are purified natural substances that have been shown to improve the pain associated with OA of the knee joints and TMJ disorders. Although hyaluronates have not been labeled by the U.S. Food and Drug Administration (FDA) for use in the TMJ, the evidence from randomized controlled trials indicates that this treatment has a beneficial effect in individuals with osteoarthritis or disc disorders of the TMJ.

Description of Disease(s)

OA is a degenerative condition of the joints and is the most common form of arthritis. OA commonly affects the hands and the weight-bearing joints, such as the knees, hips, feet and spine. OA affects an estimated 27 million Americans, mostly at or after 50 years of age, and occurs in women more commonly than men (Lawrence, 2008). Afflicted joints experience loss of synovial fluid, a protective substance which aids in absorbing shock and lubrication in the joints. Low synovial fluid levels and other mechanisms cause a progressive breakdown of the cartilage lining the ends of bones that are necessary for proper cushioning and smooth function of joints. Because of this breakdown of cartilage, bones rub against each other causing pain, loss of movement, and further destruction of the joint. The severity of OA can range from very mild to very severe.

According to the National Institute of Dental and Craniofacial Research of the National Institutes of Health, over 10 million people in the United States suffer from TMJ problems at any given time. The TMJ is the joint where the lower jaw connects to the skull. There are two matching joints, one on each side of the skull, located just in front of the ears. Additionally, the term "TMJ" may be used to refer to any disorders or symptoms related to this joint. Such symptoms include popping sounds in the jaw, inability to fully open the mouth, jaw pain or locking, headaches, earaches, toothaches, and various other types of facial pain. Many TMJ-related symptoms are caused by the effects of physical and emotional stress on the structures around the joint. These structures include the muscles of the jaw, face, and neck; the teeth, the cartilage disc in the joint space and nearby ligaments, blood vessels and nerves. In most individuals, pain associated with the TMJ is a result of displacement of the cartilage disc that cushions the joint which causes pressure and stretching of the associated sensory nerves. Popping or clicking occurs when the disc snaps out of and back into place when the jaw moves. The term "reducing disc displacement" is frequently used to describe the condition where the displaced disc returns to its normal position following displacement. Non-reducing disc displacement refers to situations where the disc does not return to its normal position, commonly resulting in a "locked" jaw or limited range of motion.

Intra-articular injections: A medical procedure using a hypodermic needle to inject a substance, such as a drug, into the space between two bones.

Osteoarthritis: A degenerative condition of the joints that causes destruction of the material in the joints that absorbs shock and allows proper movement.

Reducing and non-reducing disc displacement: In the TMJ there is a disc of cartilage that cushions the area where the skull and lower jaw meet. In some TMJ conditions this disc becomes loose and moves in the joint space, causing clicking, popping, or locking of the joint. When the disc is reduced it returns to the correct position after being displaced. In non-reducing disease the disc does not return to its proper position.

Temporomandibular joint (TMJ): The joint where the lower jaw meets the skull.

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 may be Medically Necessary when criteria are met:

When services are Investigational and Not Medically Necessary:
For the procedure codes listed above, for all other diagnoses except those listed below related to knee conditions (which are excluded from this document); or when the code describes a procedure indicated in the Position Statement section as investigational and not medically necessary.

Future ICD-10 coding (effective 10/01/2013)
A draft of ICD-10 Coding related to this document, as it might look today, is available for reference and comments at: Appendix 1: Future ICD-10 coding

Peer Reviewed Publications:

1. Alpaslan GH, Alpaslan C. Efficacy of temporomandibular joint arthrocentesis with and without injection of sodium hyaluronate in treatment of internal derangements. J Oral Maxillofac Surg. 2001; 59(6):613-618.
2. Bertolami CN, Gay T, Clark GT, et al. Use of sodium hyaluronate in treating temporomandibular joint disorders: a randomized, double-blind, placebo-controlled clinical trial. J Oral Maxillofac Surg. 1993; 51(3):232-242.
3. Bjornland T, Gjaerum AA, Moystad A. Osteoarthritis of the temporomandibular joint: an evaluation of the effects and complications of corticosteroid injections compared with injection with sodium hyaluronate. J Oral Rehabil. 2007; 34(8):583-589.
4. 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. 2008; 90(5):970-979.
5. Cohen MM, Altman RD, Hollstrom R, et al. Safety and efficacy of intra-articular sodium hyaluronate (Hyalgan) in a randomized, double-blind study for osteoarthritis of the ankle. Foot Ankle Int. 2008; 29(7):657-663.
6. Fernandez Lopez JC, Ruano-Ravina A. Efficacy and safety of intraarticular hyaluronic acid in the treatment of hip osteoarthritis: a systematic review. Osteoarthritis Cartilage. 2006; 14(12):1306-1311.
7. Fuchs S, Monikes R, Wohlmeiner A, Heyse T. Intra-articular hyaluronic acid compared with corticoid injections for the treatment of rhizarthrosis. Osteoarthritis Cartilage. 2006; 14(1):82-88.
8. Hepguler S, Akkoc YS, Pehlivan M, et al. The efficacy of intra-articular sodium hyaluronate in patients with reducing displaced disc of the temporomandibular joint. J Oral Rehabil. 2002; 29(1):80-86.
9. Karatosun V, Unver B, Ozden A, et al. Intra-articular hyaluronic acid compared to exercise therapy in osteoarthritis of the ankle. A prospective randomized trial with long-term follow-up. Clin Exp Rheumatol. 2008; 26(2):288-294.
10. Lawrence RC, Felson DT, Helmick CG, et al. Estimates of the prevalence of arthritis and other rheumatic conditions in the United States. Part II. Arthritis Rheum. 2008; 58(1):26-35.
11. Noël E, Hardy P, Hagena FW, et al. Efficacy and safety of Hylan G-F 20 in shoulder osteoarthritis with an intact rotator cuff. Open-label prospective multicenter study. Joint Bone Spine. 2009; 76(6):670-673.
12. Qvistgaard E, Christensen R, Torp-Pedersen S, Bliddal H. Intra-articular treatment of hip osteoarthritis: a randomized trial of hyaluronic acid, corticosteroid, and isotonic saline. Osteoarthritis Cartilage. 2006; 14(2):163-170.
13. Richette P, Ravaud P, Conrozier T, et al. Effect of hyaluronic acid in symptomatic hip osteoarthritis: a controlled, randomized, double-blind pilot. Arthritis Rheum. 2009; 60(3):824-830.
14. Salk RS, Chang TJ, D'Costa WF, et al. Sodium hyaluronate in the treatment of osteoarthritis of the ankle: a controlled, randomized, double-blind pilot. J Bone Joint Surg Am. 2006; 88(2):295-302.
15. Stahl S, Karsh-Zafrir I, Ratzon N, Rosenberg N. Comparison of intraarticular injection of depot corticosteroid and hyaluronic acid for treatment of degenerative trapeziometacarpal joints. J Clin Rheumatol. 2005; 11(6):299-302.
16. van den Bekerom MP, Lamme B, Sermon A, Mulier M. What is the evidence for viscosupplementation in the treatment of patients with hip osteoarthritis? Systematic review of the literature. Arch Orthop Trauma Surg. 2008; 128(8):815-823.
17. Witteveen AG, Sierevelt IN, Blankevoort L, et al. Intra-articular sodium hyaluronate injections in the osteoarthritic ankle joint: effects, safety and dose dependency. Foot Ankle Surg. 2010; 16(4):159-163.

Government Agency, Medical Society, and Other Authoritative Publications:

1. American College of Rheumatology Subcommittee on Osteoarthritis Guidelines 2000. Recommendations for the Medical Management of Osteoarthritis of Hip and Knee. Arthritis Rheum. 2000; 43(9):1905-1915.

1. Arthritis Foundation. Osteoarthritis: Available at: http://www.arthritis.org/conditions/DiseaseCenter/oa.asp. Accessed on May 12, 2011.
2. National Institute of Dental and Craniofacial Research of the National Institutes of Health. TMJ (Temporomandibular Joint and Muscle Disorders). Available at: http://www.nidcr.nih.gov/OralHealth/Topics/TMJ/. Accessed on May 12, 2011.
3. National Library of Medicine. Health Encyclopedia: Osteoarthritis. Available at: http://www.nlm.nih.gov/medlineplus/ency/article/000423.htm. Accessed on May 12, 2011.
4. National Library of Medicine. Health Encyclopedia: TMJ disorders. Available at: http://www.nlm.nih.gov/medlineplus/ency/article/001227.htm. Accessed on May 12, 2011.

Euflexxa^®
Gel-One^®
High Molecular Weight Hyaluronan
Hyalgan^®
Hylan G-F 20
Nuflexxa™
Orthovisc^®
Sodium Hyaluronate
Supartz^®
Synvisc^®
Synvisc-One^®

The use of specific product names is illustrative only.  It is not intended to be a recommendation of one product over another, and is not intended to represent a complete listing of all products available.