Of 203 patients who underwent cardiac transplantation and were given long-term treatment with cyclosporine and 0.3 mg/kg per day prednisone, 123 were studied prospectively for at least 6 months and 46 for up to 2 years to evaluate the effects on lumbar bone mineral density (BMD) and calcium metabolism of a combined therapy with calcium, calcidiol and disodium monofluorophosphate (MFP). The population was arbitrarily assigned to one of two groups. Group I consisted of patients who had a lumbar spine BMD Z score above -1.5 SD as compared with an age- and sex-matched population and no vertebral fractures. They received daily 1 g elemental calcium and 25 micrograms (1000 IU) calcidiol. Group II consisted of patients who received daily the same doses of calcium and calcidiol combined with 200 mg MFP, and was divided into two subgroups: (a) osteopenic subjects who had a lumbar spine BMD Z score below -1.5 SD without vertebral fractures and (b) osteoporotic subjects with vertebral fractures. If serum creatinine was higher than 140 mumol/l the daily dose of MFP was tapered to 100 mg. Fifty-four and 27 patients from group I and 38 and 19 patients from group II were followed respectively for 12 and 24 months. In both groups serum parathyroid hormone levels were significantly reduced from the twelfth month in parallel with a significant increase in serum 25-OHD levels. No decline in lumbar BMD occurred in non-osteopenic and non-osteoporotic patients (group 1) who received the calcium and calcidiol supplement. In group II, where MFP was added, a significant and linear increase in lumbar BMD was observed.(ABSTRACT TRUNCATED AT 250 WORDS)