SKELETAL EFFECTS OF LOW-DOSE CYCLOSPORINE-A IN AGED MALE RATS - LACK OF RELATIONSHIP TO SERUM TESTOSTERONE LEVELS

The aim of this study was to investigate the skeletal effects of cyclo sporin A (CsA) in a dose range relevant to clinical medicine in lumbar vertebral cancellous bone of aged male rats and to correlate these ef fects with possible changes in serum testosterone levels. Thirty-one 1 8-month-old male Wistar rats were divided into four weight-matched gro ups and subcutaneously injected with either 0, 1, 3, or 5 mg of CsA/kg of body, weight three times per week After 4 weeks of treatment, all rats were killed after in vivo fluorochrome labelling and the first lu mbar vertebrae analysed by quantitative histomorphometry, Serum was an alysed for total calcium, creatinine, alkaline phosphatase, osteocalci n, parathyroid hormone, total testosterone, and CsA levels, CsA admini stration resulted in a dose-dependent increase in serum osteocalcin le vels and in histomorphometric indices of cancellous bone turnover in t he axial skeleton. Furthermore, CsA-treated rats showed a deterioratio n of vertebral cancellous bone structure with increased discontinuity of the trabecular bone network due to trabecular plate perforations. S erum testosterone levels were not significantly changed by CsA treatme nt and were uncorrelated to all biochemical or histomorphometric indic es of bone turnover. We conclude that the 4-week administration of CsA at doses that are close to those used in transplantation patients ind uced high turnover osteopenia in the axial skeleton of aged, 18-month- old male rats, and that these effects were likely not mediated by chan ges in serum testosterone levels.