Skeletal Effects of Low‐Dose Cyclosporin A in Aged Male Rats: Lack of Relationship to Serum Testosterone Levels

• Published in: Journal of bone and mineral research Vol. 13; no. 1; pp. 79 - 87
• Main Authors: Erben, Reinhold G., Stangassinger, Manfred, Gärtner, Roland
• Format: Journal Article
• Language: English
• Published: Washington, DC John Wiley and Sons and The American Society for Bone and Mineral Research (ASBMR) 01.01.1998; American Society for Bone and Mineral Research
• Subjects: Aging - drug effects; Aging - physiology; Animals; Biological and medical sciences; Body Weight - drug effects; Bone and Bones - drug effects; Bone and Bones - metabolism; Calcification, Physiologic - drug effects; Cell Count - drug effects; Cyclosporine - administration & dosage; Cyclosporine - pharmacology; Eating - drug effects; Immunomodulators; Injections, Subcutaneous; Linear Models; Male; Medical sciences; Osteoclasts - cytology; Osteoclasts - metabolism; Osteoclasts - physiology; Osteogenesis - drug effects; Pharmacology. Drug treatments; Rats; Rats, Wistar; Space life sciences; Testosterone - blood; Animal model; Androgen; Rat; Low dose; Rodentia; Male; Vertebra; Osteoarticular system; Testosterone; Vertebrata; Chemotherapy; Mammalia; Treatment; Animal; Ciclosporin; Testicular hormone; Immunosuppressive agent; Bone; Spongious bone; Sex steroid hormone
• ISSN: 0884-0431; 1523-4681
• DOI: 10.1359/jbmr.1998.13.1.79

The aim of this study was to investigate the skeletal effects of cyclosporin A (CsA) in a dose range relevant to clinical medicine in lumbar vertebral cancellous bone of aged male rats and to correlate these effects with possible changes in serum testosterone levels. Thirty‐one 18‐month‐old male Wistar rats were divided into four weight‐matched groups 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 labeling and the first lumbar vertebrae analyzed by quantitative histomorphometry. Serum was analyzed for total calcium, creatinine, alkaline phosphatase, osteocalcin, parathyroid hormone, total testosterone, and CsA levels. CsA administration resulted in a dose‐dependent increase in serum osteocalcin levels and in histomorphometric indices of cancellous bone turnover in the axial skeleton. Furthermore, CsA‐treated rats showed a deterioration of vertebral cancellous bone structure with increased discontinuity of the trabecular bone network due to trabecular plate perforations. Serum testosterone levels were not significantly changed by CsA treatment and were uncorrelated to all biochemical or histomorphometric indices of bone turnover. We conclude that the 4‐week administration of CsA at doses that are close to those used in transplantation patients induced high turnover osteopenia in the axial skeleton of aged, 18‐month‐old male rats, and that these effects were likely not mediated by changes in serum testosterone levels.