Amelioration of disease severity by intraarticular hylan therapy in bilateral canine osteoarthritis

Because of its high molecular weight, the glycosaminoglycan molecule hyalur onan is responsible for the viscoelastic properties of normal synovial flui d. In osteoarthritis, the concentration and molecular weight of hyaluronan in synovial fluid is diminished; this impairs the ability of synovial fluid to effectively lubricate joints, absorb loads, and exert anti-inflammatory effects. Using a bilateral anterior cruciate ligament transection and part ial neurectomy canine model of osteoarthritis, this study examined the effe ct of viscosupplementation with hylan G-F 20 as a treatment for osteoarthri tis. Twelve dogs underwent bilateral arthroscopic anterior cruciate-ligamen t transections and partial neurectomy of the knee joints. Beginning 1 week after the operation, six dogs received three weekly 500-mu l injections of hylan G-F 30 in one knee and a sham injection of saline solution in the con tralateral knee (early-treatment group). The remaining six animals underwen t the same treatment 2 months following the procedure (late-treatment group ). All dogs were killed at 8 months, and both knees were evaluated for gros s pathology, histology, and proteoglycan content. In addition, with use of 500-MHz [H-1] magnetic resonance spectroscopy, the synovial fluid from both knees was assessed for changes in metabolic profile. Differences in outcom e were analyzed with paired t tests. Gross pathological and histological ex amination revealed significantly less severe changes of osteoarthritis in k nees treated with hylan G-F 20 2 months after surgery than in the contralat eral untreated knees. Magnetic resonance spectroscopy of the specimens in t his late-treatment group showed significantly decreased glucose concentrati ons and significantly elevated isoleucine levels in the synovial fluid from knees treated with hylan G-F 20 compared with the controls. Previous magne tic resonance spectroscopy had shown that glucose concentrations increase w ith the onset of osteoarthritis and eventually diminish in end-stage osteoa rthritis. The three injections of hylan were given after osteoarthritis was established, and the severity of the disease was ameliorated in the treate d knees 6 months after treatment, This occurred although hylan G-F 20 is al most certainly cleared from joints by lymphatics within 4 weeks of injectio n, suggesting that hylan therapy can retard the progression of osteoarthrit is for periods of time extending beyond the intraarticular residence time o f the injected molecules and that hylan injections given at relatively earl y stages of osteoarthritis may have a chondroprotective effect. No changes in outcome were noted in the animals that received hylan G-F 20 immediately following surgery.