Morphological analysis of knee synovial membrane biopsies from a randomized controlled clinical study comparing the effects of sodium hyaluronate (Hyalgan (R)) and methylprednisolone acetate (Depomedrol (R)) in osteoarthritis

Objective. The study was part of a randomized open-label clinical trial des igned to evaluate the effects of intra-articular injections of hyaluronan ( Hyalgan(R)) (HY) in osteoarthritis (OA) of the human knee. Data were compar ed with these obtained after treatment with methylprednisolone acetate (Dep omedrol(R)) (MP). Methods. Synovial membranes from patients with OA of the knee, primary or s econdary to a traumatic event and classified according to the American Coll ege of Rheumatology criteria, were examined by arthroscopy and by light and electron microscopy before and 6 months after local injection of HY (2 ml of 500-730 000 MW hyaluronan, 10 mg/nl in saline, one injection per week fo r 5 weeks) or MP (1 ml of methylprednisolone acetate, 40 mg/ml, one injecti on per week for 3 weeks). Results. Arthroscopy revealed a significant decrease in inflammatory score after both treatments. Histology showed that HY treatment was effective (P less than or equal to 0.05) in reducing the number and aggregation of linin g synoviocytes, as well as the number and calibre of the vessels. MP treatm ent significantly reduced the number of mast cells in primary OA. Both trea tments tended to decrease the number of hypertrophic and to increase the nu mber of fibroblast-hike lining cells, to decrease the numbers of macrophage s, lymphocytes, mast cells and adipocytes, and to decrease oedema, especial ly in primary OA, and to increase the number of fibroblasts and the amount of collagen. These phenomena were evident throughout the thickness of the s ynovial tissue. Conclusion. At least in the medium term, both HY and MP modified a number o f structural variables of the synovial membrane of the osteoarthritic human knee towards the appearance of that of normal synovium. The effect was mor e evident in primary OA than in OA secondary to a traumatic event. This is the first evidence that local hyaluronan injections modify the structural o rganization of the human knee synovium in OA.