SKELETAL GROWTH AND BONE-DENSITY AS SENSITIVE PARAMETERS IN EXPERIMENTAL ARTHRITIS - EFFECT OF CYCLOSPORINE-A

Osteopenia and retarded skeletal growth are consistent features of juv enile polyarthritis. Although the former has also been described in th e experimental animal, the consequences of induced joint inflammation on skeletal growth have not yet been documented. In order to investiga te the effect of experimental arthritis on these parameters, we studie d female rats with adjuvant arthritis (AA) subjected to chronic treatm ent with cyclosporin A (CsA, Sandimmun(R)). This compound has been fou nd to prevent the development of articular swelling and also repair jo int and skeletal lesions in AA rats. Five groups of 8 animals each rec eived oral CsA, 2.5, 5, 10, 20, or 30 mg/kg daily for 30 days. Eight n ormal and eight diseased, untreated rats served as placebo controls. T he parameters studied were (a) measurement of hindpaw swelling, (b) ra diometric assessment of vertebral growth, (c) vertebral trabecular den sity, (d) weight control and nutritional status. At the end of the inv estigational period, AA-rats on no therapy had severe osteopenia and g rowth retardation. Treatment with CsA, 2.5 mg/kg, was ineffective, but doses between 5 and 20 mg/kg prevented the development of articular a nd osseous lesions and normalized growth. A catch-up phenomenon was al so observed. The 20 mg/kg dose showed no better effect than 10 mg/kg, and 30 mg/kg produced a significant reduction in bone density and skel etal growth, an effect thought to be toxic in nature. Body weight para lleled growth profiles, and average food consumption was stable in all groups with the exception of somewhat low records in the animals rece iving 30 mg/kg. A comparison with classical features of human juvenile arthritis indicated that the clinical and radiological profiles conce rning joint swelling, osteopenia, skeletal growth, and response to tre atment, occur in a similar fashion, although it cannot be inferred tha t the operating mechanisms are common to both situations. It is conclu ded that skeletal growth measurements may represent a sensitive additi onal parameter in the evaluation of experimental arthritis and its res ponse to potential therapeutic agents.