The aims of this study were to evaluate bone metabolism in primary biliary cirrhosis (PBC) and the effect of ADFR (activate, depress, free, repeat) therapy with vitamin D, calcium and calcitonin in preventing bone resorption. Sixty-nine female subjects entered the study: 38 PBC (AMA + ve) patients, 11 AMA-negative chronic liver disease patients and 20 age-matched healthy controls. Bone metabolism was evaluated by biochemical parameters and dual-photon absorptiometry of the lumbar spine at time 0, 6 and 18 months. Both PBC and chronic liver disease (CLD) patients showed low levels of serum 25-hydroxyvitamin D, osteocalcin and bone mineral content expressed as AAD (average area density) compared to healthy controls. Serum parathyroid hormone in PBC patients was at the lower limit of the normal range and was significantly lower than patients with chronic liver disease. At a 6-month interval, AAD significantly decreased in PBC patients (p less than 0.005). At the 6-month period PBC patients were allocated into two groups according to a cut-off AAD of 0.800 g/cm2: group A (no treatment, AAD greater than 0.800, n = 11), group B (treatment, AAD less than 0.800, n = 13). The latter group received a 4-week course with oral calcium carbonate (1500 mg daily) + oral 1,25-dihydroxyvitamin D (0.5 micrograms twice a day for 5 days) + carbocalcitonin (40 U MRC) i.m. thrice a week. The treatment was repeated with the same protocol at 2-month intervals for 12 months.(ABSTRACT TRUNCATED AT 250 WORDS)