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.