INFLUENCE OF AGE ON CYCLOSPORINE-A-INDUCED ALTERATIONS IN BONE-MINERAL METABOLISM IN THE RAT IN-VIVO

Cyclosporin A (CsA) administered to actively growing young rats produc es a high-turnover osteopenia. We investigated and compared the effect of CsA on the bone mineral metabolism in young rats with that of olde r rats, which have a lower rate of bone turnover. A group of 24 young (9 weeks) and 24 older (9 months) male Sprague-Dawley rats were orally administered 15 mg/kg of CsA or placebo daily for 24 days. Rats were weighed and serum assayed serially for bone gla protein (BGP), parathy roid hormone, ionized calcium, blood urea nitrogen, creatinine, and 1, 25-dihydroxyvitamin D [1,25-(OH)(2)D]. After sacrifice, histomorphomet ric analysis was performed on undecalcified proximal tibial metaphysis with double-fluorescent labeling. Serum BGP levels were significantly elevated in both young and older rats administered CsA, and 1,25-(OH) (2)D levels were significantly elevated in CsA-treated young rats more than in older rats. Body weight was significantly reduced in CsA-trea ted older rats. There were mild but significant alterations in renal f unction in both groups receiving CsA. In the most comprehensive examin ation to date of the effects of CsA on bone histomorphometry, both you ng (-44%) and older rats (-20%) lost significant amounts of trabecular bone compared to their respective controls. Bone loss in young rats w as mainly due to a reduced number of trabeculae; older rats lost mainl y trabecular thickness. Microanatomic nodal studies were consistent wi th these results. These data demonstrate that although cancellous bone loss induced by CsA is more marked in young Fats, older rats with slo wer bone turnover are also at risk.