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Bone Loss and Turnover after Cardiac Transplantation¹

Departments of Medicine (E.S., M.R., S.J.S., D.M., K.A., V.A.), Surgery (R.E.M.), and Radiology (R.B.S.), College of Physicians and Surgeons, and Division of Biostatistics, School of Public Health (S.H.L.), Columbia University, New York, New York 10032; and the Department of Medicine, University of Heidelberg (M.J.S.), Heidelberg, Germany

Address all correspondence and requests for reprints to: Elizabeth Shane, M.D., Department of Medicine, Columbia University College of Physicians and Surgeons, 630 West 168th Street, New York, New York 10032.

Cardiac transplantation is associated with increased prevalence and incidence of fracture, and rapid bone loss has been reported during the first posttransplant year. To define further the pattern and etiology of bone loss after cardiac transplantation, we enrolled 70 patients (52 men and 18 women) in a prospective 3-yr study. Bone densitometry (BMD) and biochemical indexes of mineral metabolism were performed before and at defined times after transplantation. Despite supplementation with elemental calcium (1000 mg/day) and vitamin D (400 IU/day), the mean rate of bone loss during the first year was 7.3 ± 0.9% (±SEM) at the lumbar spine and 10.5 ± 1.1% at the femoral neck. The rate of bone loss slowed (P < 0.001 compared to year 1) at both sites (0.9 ± 0.9% and 0.1 ± 1.0%, respectively) during the second year. During the third year, lumbar spine BMD increased at a rate of 2.4 ± 0.8%/yr (P < 0.02 compared to year 2), but femoral neck BMD did not change. At the radius, the rate of decline in BMD was negligible during the first year (0.9 ± 0.5%), but was significant during the second (2.1 ± 0.6%; P < 0.01) and third (2.9 ± 0.8%; P < 0.03) years. Evaluation of the pattern of bone loss during the first year demonstrated that mean lumbar spine BMD decreased rapidly during the first 6 months, after which there was no further decline. In contrast, femoral neck BMD continued to fall at an annualized rate of 8.2 ± 1.3% during the second half of the year. The pattern and rates of bone loss were similar in men and women. Biochemistries revealed decreases in serum testosterone and osteocalcin and increases in all bone resorption markers 1 and 3 months after transplantation, with a return to baseline by 6 months. Higher rates of bone loss were associated with greater exposure to prednisone, lower serum concentrations of vitamin D metabolites, greater suppression of osteocalcin, higher levels of bone resorption markers, and, in men, lower serum testosterone concentrations.

We conclude that rapid bone loss is primarily confined to the initial year after transplantation. During the first 6 months, bone loss is accompanied by alterations in markers of bone turnover consistent with biochemical uncoupling of bone formation and resorption. Greater exposure to glucocorticoids, lower serum concentrations of vitamin D metabolites and testosterone, and higher bone turnover were associated with more rapid bone loss.

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