Mechanisms of bone loss after cardiac transplantation.

To determine the mechanism of bone loss after cardiac transplantation (CTX), we studied 50 men 0.5-47 months after CTX (ages 18-64 years) who received prednisolone and cyclosporin to prevent rejection, and 40 healthy men as controls (ages 20-70 years). We measured bone mineral density (BMD) using dual-energy X-ray absorptiometry (DXA), bone resorption using urinary cross-linked N-terminal telopepides of type I collagen (NTx), and bone formation using osteocalcin (BGP) and bone alkaline phosphatase (BAP). The results from the controls were used to calculate z scores. BMD was significantly decreased at the lumbar spine, femoral neck, and total body, and bone turnover was significantly increased as assessed by NTx/creatinine, BGP, and BAP as compared with controls (p < 0.01 for all measurements). To evaluate the cause of the increased bone turnover we measured serum parathyroid hormone (PTH) by IRMA, and this was also elevated (p < 0.001). There was a significant correlation between serum PTH and BGP (r = 0.58, p < 0.01). To evaluate the cause of the increase in PTH, we measured serum calcium and it was decreased (p < 0.001), serum phosphorus was increased (p < 0.001), serum creatinine was increased (p < 0.001), and serum 1,25-dihydroxyvitamin D3 [1,25(OH)2D, RIA] was decreased (p = 0.03). Serum PTH correlated weakly with serum calcium (r = -0.41, p < 0.003) and with serum creatinine (r = 0.35, p = 0.01). There was a weak, but significant, correlation between serum creatinine and 1,25(OH)2D3 (r = 0.33, p = 0.03). Serum levels of testosterone and dehydroapiandrosterone sulfate were decreased after CTX but did not correlate with any other parameters. There was a weak negative correlation between prednisolone daily dose and serum BGP level (r = 0.29, p = 0.06) in those patients whose prednisolone current dose was >7.5 mg/day. We conclude that: (1) the low BMD found after CTX is associated with increased bone turnover which results, in turn, from renal impairment; (2) prednisolone is involved in rapid bone loss, whereas mild secondary hyperparathyroidism may be a major contributor to disorder of bone remodeling after this rapid loss; and (3) decreased androgen levels may not be a major factor resulting in bone loss in men after CTX.