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

Abstract

Because of its high molecular weight, the glycosaminoglycan molecule hyaluronan is responsible for the viscoelastic properties of normal synovial fluid. 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 partial neurectomy canine model of osteoarthritis, this study examined the effect of viscosupplementation with hylan G-F 20 as a treatment for osteoarthritis. Twelve dogs underwent bilateral arthroscopic anterior cruciate-ligament transections and partial neurectomy of the knee joints. Beginning 1 week after the operation, six dogs received three weekly 500-microl injections of hylan G-F 20 in one knee and a sham injection of saline solution in the contralateral knee (early-treatment group). The remaining six animals underwent the same treatment 2 months following the procedure (late-treatment group). All dogs were killed at 8 months, and both knees were evaluated for gross pathology, histology, and proteoglycan content. In addition, with use of 500-MHz [1H] magnetic resonance spectroscopy, the synovial fluid from both knees was assessed for changes in metabolic profile. Differences in outcome were analyzed with paired t tests. Gross pathological and histological examination revealed significantly less severe changes of osteoarthritis in knees treated with hylan G-F 20 2 months after surgery than in the contralateral untreated knees. Magnetic resonance spectroscopy of the specimens in this late-treatment group showed significantly decreased glucose concentrations and significantly elevated isoleucine levels in the synovial fluid from knees treated with hylan G-F 20 compared with the controls. Previous magnetic resonance spectroscopy had shown that glucose concentrations increase with the onset of osteoarthritis and eventually diminish in end-stage osteoarthritis. The three injections of hylan were given after osteoarthritis was established, and the severity of the disease was ameliorated in the treated knees 6 months after treatment. This occurred although hylan G-F 20 is almost certainly cleared from joints by lymphatics within 4 weeks of injection, suggesting that hylan therapy can retard the progression of osteoarthritis for periods of time extending beyond the intraarticular residence time of the injected molecules and that hylan injections given at relatively early 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.