title: Hepatic osteodystrophy in primary biliary cirrhosis: a possible defect in Kupffer cell mediated cleavage of parathyroid hormone.
abstract: Twelve of fourteen female patients with primary biliary cirrhosis, receiving vitamin D supplementation, exhibited unequivocal signs of osteoporosis but not of osteomalacia. Vitamin D treatment reproduced normal 25-hydroxyvitamin D levels in all but two patients and the 1,25 and 24,25-dihydroxyvitamin D metabolic pathways appeared to be unimpaired. A possible mechanism for the vitamin D resistant osteoporosis has been identified following the observation that, in those patients with severe cirrhosis, the circulating concentration of intact PTH was elevated. The increase in intact hormone appears to be at the expense of the carboxyl-regional PTH produced by hepatic Kupffer cell mediated cleavage of intact PTH. As a defect in Kupffer cell function is documented in primary biliary cirrhosis we postulate that the increased intact PTH/decreased carboxyl-regional PTH concentrations arise as a result of diminished Kupffer cell mediated cleavage. The reduced generation of cleaved PTH, due to this loss of Kupffer cell activity, would thus contribute to the development of osteoporosis in primary biliary cirrhosis.
mesh_terms: D015650:24,25-Dihydroxyvitamin D 3; D015652:25-Hydroxyvitamin D 2; D000328:Adult; D000368:Aged; D002117:Calcitriol / Q000097:blood; D002118:Calcium / Q000097:blood; D002762:Cholecalciferol / Q000627:therapeutic use; D004100:Dihydroxycholecalciferols / Q000097:blood; D004872:Ergocalciferols / Q000031:analogs & derivatives / Q000097:blood; D005260:Female; D006801:Humans; D007728:Kupffer Cells / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008105:Liver Cirrhosis, Biliary / Q000150:complications / Q000188:drug therapy / Q000378:metabolism*; D008875:Middle Aged; D010024:Osteoporosis / Q000209:etiology*; D010281:Parathyroid Hormone / Q000097:blood / Q000378:metabolism*
chemical_list: D004100:Dihydroxycholecalciferols; D004872:Ergocalciferols; D010281:Parathyroid Hormone; D002762:Cholecalciferol; D015652:25-Hydroxyvitamin D 2; D015650:24,25-Dihydroxyvitamin D 3; D002117:Calcitriol; D002118:Calcium