24-25-dihydroxyvitamin-d-3 and Liver-Cirrhosis--Biliary

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.

Topics: 24,25-Dihydroxyvitamin D 3; 25-Hydroxyvitamin D 2; Adult; Aged; Calcitriol; Calcium; Cholecalciferol; Dihydroxycholecalciferols; Ergocalciferols; Female; Humans; Kupffer Cells; Liver; Liver Cirrhosis, Biliary; Middle Aged; Osteoporosis; Parathyroid Hormone

The osteopenic bone disease associated with primary biliary cirrhosis is thought to be de to a deficiency in vitamin D or its metabolites. However, this has never been proven. Therefore, we measured serum levels of 25-hydroxyvitamin D3 (25-OHD3), 1,25-dihydroxyvitamin D (1,25(OD)2D), and 24,25-dihydroxyvitamin D3 (24,25(OH)2D3), before and after a 1 yr treatment with oral 25,OHD3, in 10 patients with primary biliary cirrhosis selected because of documented osteopenic bone disease. Only in 1 patient was the pretreatment serum 25-OHD3 level below normal, less than 4.4 ng/ml. In 8 patients the serum 25,OHD3 level was in the low normal range and in one, was above normal. Serum levels of 1,25(OH)2D, the vitamin D metabolite with the greatest stimulatory effect on intestinal calcium absorption, were normal in 9 patients and elevated in 1. In contrast, serum levels of 24,25-(OH)2D3, a metabolite whose function is not known with certainty, were undetectable in 8 patients, low normal in a ninth, and normal in 1 patient who had been on large amounts of vitamin D2 (50,000 U b.i.w.,) before the start of the study. After 1 yr of treatment with oral 25-OHD3, serum 25-OHD3 rose to above normal in 9 patients. Serum 1,25-(OH)2D levels did not change significantly, while 24,25-(OH)2D3 rose to normal levels or higher in 9 of 10 patients. The bone disease of primary biliary cirrhosis is not due to 25-hydroxyvitamin D deficiency alone and is certainly not due to a deficiency of 1,25-(OH)2D as has been postulated. It may be related to low blood levels of 24,25-(OH)2D3 or to other as yet undefined factors.

Topics: 24,25-Dihydroxyvitamin D 3; Adult; Bone and Bones; Calcifediol; Dihydroxycholecalciferols; Female; Humans; Hydroxycholecalciferols; Intestinal Absorption; Liver Cirrhosis, Biliary; Male; Middle Aged; Vitamin D