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The aim of this observational study was to compare the effect of calcium and alfacalcidol supplementation on the regression of hyperparathyroidism and on prevention of osteopenia in patients up to 3 years after renal transplantation. Two historical cohorts were compared for that purpose. One hundred and fifty-nine patients received calcium carbonate supplement (group 1), while 81 patients were treated with alfacalcidol (group 2). Serum Ca, phosphate (P), Mg, creatinine, alkaline phosphatase (AP) and parathyroid hormone (PTH) levels were determined before and after transplantation in the two groups, for 3 years. Femoral neck and lumbar spine bone mineral density (BMD) was measured only at 3 and 6 months and 1, 2 and 3 years after transplantation. At baseline there was no difference in age or sex ratio, but prevalence in post-menopausal women was higher in group 1 (6.9% versus 1.2%). Duration on dialysis was comparable but prevalence of interstitial and undetermined nephropathies was higher in group 1. Baseline serum concentrations of PTH, Ca and P were comparable in both groups. After transplantation, plasma creatinine decreased to comparable levels in both groups. Immunosuppression by triple therapy was more prevalent in group 2, so that cumulative dose of steroid was higher in group 1, especially at 1 month because of higher incidence of acute rejections (51% versus 13%). Mean intact PTH levels decreased in both groups, from 18 pmol/l to 8.4 and 7.9 at 3 years, but the decrease was significantly greater with alfacalcidol at 6 and 12 months. At 3 months, BMD were comparable at both sites. From 3 months to 3 years after kidney transplantation, mean lumbar spine BMD significantly increased from 0.963 to 1.054 g/cm2 in group 1, whereas there was no significant decrease (1.048 to 1.006 g/cm2) in group 2, the difference in changes being significant (P<0.05). Femoral neck BMD was not significantly increased in either group (0.932 to 0.993 g/cm2 in group 1, and 0.850 to 0.907 g/cm2 in group 2). Expressed as percentages, these changes were +9.4% and –4% for lumbar BMD and +6.5% and +6.7% for femoral neck, for groups 1 and 2, respectively. Prevalence of osteopenia was not significantly lower at 3 years in group 1 (45% and 51%) than in group 2. During the follow-up period, osteonecrosis was diagnosed in six patients (3.8%) in group 1 and in nine (11%) in group 2. In conclusion, alfacalcidol compared to CaCO3 supplement suppressed hyperparathyroidism more rapidly and strongly. In spite of higher osteopenia risk in the CaCO3 group, lumbar BMD increase was greater and incidence of osteonecrosis higher in this group, suggesting better bone protection with CaCO3 than with alfacalcidol. [ABSTRACT FROM AUTHOR]