RATES OF CANCELLOUS BONE REMODELING AND TURNOVER IN OSTEOPENIA ASSOCIATED WITH PRIMARY BILIARY-CIRRHOSIS

Osteoporosis and fracturing are well-recognized manifestations of primary biliary cirrhosis (PBC), but the abnormalities of bone remodeling and turnover that result in bone loss are poorly understood. We used dynamic histomorphometric techniques to measure tissue level rates of cancellous bone resorption, formation, and turnover in 12 premenopausal women with PBC and in 12 normal premenopausal women. We compared these values with estimates of bone resorption and formation obtained concurrently in the same subjects by radiocalcium kinetics and biochemical markers. Rates of bone turnover were analyzed as a function of a risk score that reflects the severity of hepatic disease and cholestasis (Mayo proportional-hazards model). Positive correlations were observed between tissue level and whole skeletal estimates of bone remodeling. At the remodeling site (bone multicellular unit [BMU]), the depth of eroded lacunae was unaltered by PBC, but wall thickness was decreased. At the level of bone tissues, mean bone turnover was increased in PBC patients but varied widely and increased as hepatic disease and cholestasis worsened. We conclude that PBC causes a reduction in the volume of bone formed at the remodeling site and that the overall level of bone remodeling and turnover in PBC is strongly influenced by the severity of hepatic disease and cholestasis. We hypothesize that the rate of bone loss in PBC may be decreased by therapeutic agents that slow bone turnover, and that further bone loss may be halted by liver transplantation.