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Longterm Effects of Intraarticular Hyaluronan on Synovial Fluid in Osteoarthritis of the Knee



Objective. Intraarticular (IA) hylan injections constitute second-line therapy for osteoarthritis (OA) of the knee, but human studies suggesting a possible mechanism of action are lacking. We examined the effect of IA Hylan GF-20 injections on synovial fluid (SF) hyaluronan (HA) concentration, viscosity, and elasticity over a 6-month period in patients with mild to moderate OA of the knees.

Methods. Patients with symptomatic knee OA (Osteoarthritis Research Society International grade 1–2) had SF aspirated from the study knee pre- and 3 and 6 months post-Hylan injection. Primary endpoints included SF HA concentration, viscosity, and elasticity. SF HA concentration was determined using uronic acid assay, and rheology measured using a micro-Fourier rheometer.

Results. Sequential SF samples were available from 32 of 60 subjects injected at baseline (15 men, 17 women; mean age 65 yrs) at 3 months post-injection. The mean HA concentration had increased by 13% (p < 0.0008), and the complex shear modulus had increased by 16% (p < 0.03). Sufficient SF was also available from 19 of these subjects at 6 months post-injection when mean HA concentration was 2.24 ± 0.62 mg/ml compared to their baseline mean of 2.02 ± 0.52 mg/ml, an increase of 10% (p < 0.053).

Conclusion. This open-label study showed a statistically significant change from baseline in both SF HA concentration and complex shear modulus at 3 months following IA Hylan GF-20 injection among subjects with mild to moderate knee OA. These results suggest that one possible mechanism of action of viscosupplementation is to promote endogenous HA production. Longer-term studies are required to identify whether these changes in SF measures are important for modification of disease progression in knee OA. (J Rheumatol 2006;33:946–50)

Key Indexing Terms:


From the University of Sydney Institute of Bone and Joint Research, Royal North Shore Hospital, St. Leonards, NSW, Australia.

Supported by a grant from Bayer Pharmaceuticals Australia and Genzyme Corporation.

H. Bagga, BMed, FRACP; D. Burkhardt, BSc; P. Sambrook, MD, FRACP; L. March; MBBS, MSc, PhD, FRACP, FAFPHM, Institute of Bone and Joint Research, Royal North Shore Hospital.

Address reprint requests to Prof. L. March, Institute of Bone and Joint Research, Royal North Shore Hospital, St. Leonards, NSW 2065, Australia.

Accepted for publication January 2, 2006.

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© 2006. The Journal of Rheumatology Publishing Company Limited.
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