High prevalence of osteoporosis in cardiac transplant recipients and discordance between biochemical turnover markers and bone histomorphometry

OBJECTIVE All patients attending the cardiac transplantation clinic at the Royal Perth Hospital were investigated to determine the prevalence of osteoporosis and to assess changes in bone metabolism and histomorphometry in a cohort of cardiac transplant recipients. DESIGN Retrospective cross-sectional study. PATIENTS Thirty-two patients (27 male; 5 female) who had received a cardiac transplant during the past 10 years and who were receiving immunosuppressive therapy with cyclosporin, azathioprine and prednisolone were studied. MEASUREMENTS All patients had bone densitometry by DEXA of the lumbar spine and femoral neck and X-rays of the thoracolumbar spine. Pasting serum ionized calcium, intact PTH, creatinine, 25 hydroxyvitamin D, alkaline phosphatase, osteocalcin, testosterone and free thyroxine and urine calcium, creatinine, hydroxyproline and deoxypyridinoline were measured. Six osteoporotic patients consented to transiliac bone biopsy following double tetracycline labelling. RESULTS Osteoporosis was present at the lumbar spine in eight patients, femoral neck in seven patients and was present at one or more sites in 13 patients (41%). Seven patients (22%) had vertebral fractures which were asymptomatic in five patients. Secondary hyperparathyroidism was present in 16 patients (53%) but significant renal failure (creatinine clearance < 70 ml/min) was only found in 8 (50%). Levels of biochemical markers of bone turnover were increased in 23 patients (72%). Serum osteocalcin (P = 0.02) and alkaline phosphatase (P = 0.04) were significantly higher in osteoporotic patients than in nonosteoporotic patients. Histomorphometric findings varied markedly between patients. Microscopic features of hyperparathyroidism were not observed. CONCLUSIONS Osteoporosis and asymptomatic vertebral fractures are common following cardiac transplantation. Biochemical markers of bone turnover were increased in the majority of patients. Many had biochemical evidence of secondary hyperparathyroidism but this could be attributable to significant renal failure in only 50% of cases. Osteocalcin and alkaline phosphatase correlated inversely with bone density. Histomorphometric findings did not correlate with these biochemical changes in most cases. These results suggest that multiple factors are responsible for osteoporosis in cardiac transplant recipients. Osteocalcin and alkaline phosphatase may be useful biochemical markers, predicting patients at highest risk of fracture.