Tolerability and short-term effectiveness of hylan G-F 20 in 4253 patients with osteoarthritis of the knee in clinical practice.
Curr Med Res Opin. 2005 Aug;21(8):1261-9. 
Kemper F, Gebhardt U, Meng T, Murray C.

OBJECTIVE: To determine the tolerability and short-term effectiveness of hylan G-F 20 (Synvisc) in patients with symptomatic osteoarthritis (OA) of the knee in standard clinical practice.
RESEARCH DESIGN AND METHODS: Over 800 orthopedic surgeons in Germany recorded adverse events (AEs) for approximately five consecutive patients each following 3 weekly intra-articular hylan G-F 20 injections. Patients assessed their pain on a 4-point scale before and 3 weeks after the first injection. Potential risk factors for local AEs and possible predictors of short-term effectiveness of hylan G-F 20 were explored with logistic regression.
RESULTS: 4253 patients were treated with 12699 injections by 840 physicians at 720 sites. Local, treatment related AEs (n = 302) were reported in 180 patients (4.2% of patients; 2.4% of injections). The most frequently reported AEs were joint effusion (2.4% of patients), joint swelling (1.3%), arthralgia (1.2%), joint warmth (0.6%), and injection site erythema (0.3%). Most AEs were mild (21.4%) to moderate (40.3%) in nature. One patient experienced a serious AE of severe swelling and synovial fluid accumulation judged as possibly treatment related. Patients < 70 years old, patients with a longer time since diagnosis, and those previously treated with visco-supplementation were more likely to experience a local AE. Pain significantly (p < 0.0001) decreased 3 weeks after the first injection compared with before treatment. Potential predictors of hylan G-F 20 short-term effectiveness were being underweight, male gender, shorter time since diagnosis, and severe baseline pain.
CONCLUSIONS: In this population of 4253 patients treated with hylan G-F 20 for OA knee pain, the overall incidence of local, treatment-related AEs was low and consistent with those reported in the current US product labeling and previously published studies. Additionally, short-term effectiveness was confirmed.


The effects of hyaluronic acid on articular chondrocytes.
J Bone Joint Surg Br. 2005 Aug;87(8):1143-9.
Akmal M, Singh A, Anand A, Kesani A, Aslam N, Goodship A, Bentley G.

The purpose of this study was to examine the effects of hyaluronic acid supplementation on chondrocyte metabolism in vitro. The clinical benefits of intra-articular hyaluronic acid injections are thought to occur through improved joint lubrication. Recent findings have shown that exogenous hyaluronic acid is incorporated into articular cartilage where it may have a direct biological effect on chondrocytes through CD44 receptors.Bovine articular chondrocytes were isolated and seeded into alginate constructs. These were cultured in medium containing hyaluronic acid at varying concentrations. Samples were assayed for biochemical and histological changes.There was a dose-dependent response to the exposure of hyaluronic acid to bovine articular chondrocytes in vitro. Low concentrations of hyaluronic acid (0.1 mg/mL and 1 mg/mL) significantly increase DNA, sulphated glycosaminoglycan and hydroxyproline synthesis. Immunohistology confirmed the maintenance of cell phenotype with increased matrix deposition of chondroitin-6-sulphate and collagen type II. These findings confirm a stimulatory effect of hyaluronic acid on chondrocyte metabolism.