CYCLOSPORINE-A INCREASES THE BIOCHEMICAL MARKERS OF BONE REMODELING IN PRIMARY BILIARY-CIRRHOSIS

To assess whether cyclosporin A has any influence on the bones of pati ents with primary biliary cirrhosis, bone mineral density, vertebral f ractures and biochemical and hormonal parameters of bone mineral metab olism were evaluated in 38 female patients with primary biliary cirrho sis who, 7 to 47 months previously, had been randomized to receive cyc losporin A (n=18) or placebo (n=20). Bone mineral density and vertebra l fractures were reevaluated after 12 to 47 months in 19 of these pati ents (ten with cyclosporin and nine with placebo). Serum osteocalcin l evels in patients taking cyclosporin (median, range: 7.8, 4.2-16 ng/ml ) were similar to healthy female controls (6.0, 4.7-9.5 ng/ml), and si gnificantly higher than in patients receiving placebo (5.4, 1.0-8.6 ng /ml, p<0.02). Patients treated with cyclosporin showed a higher urinar y hydroxyproline/creatinine ratio (0.097, 0.025-0.138) than patients w ith placebo (0.031, 0.022-0.044) (0.05> p<0.1), and healthy controls ( 0.032, 0.021-0.048) 01<0.001). Urinary hydroxyproline was above normal levels in six of nine patients treated with cyclosporin. Circulating parathyroid hormone levels were also higher in patients treated with c yclosporin (4.3, 2.0-9.0 pmol/l) than in those with placebo (3.1, 1.1- 5.1 pmol/l) (p<0.001), and healthy controls (2.9, 1.1-6.9 pmol/ 1) (p< 0.001). In four patients treated with cyclosporin the parathyroid horm one levels were above normal values. No patient had renal failure. Amo ng the 19 patients who were studied on two occasions, no significant b one mineral density changes were observed in ten patients treated with cyclosporin (1.012, 0.693-1.269 vs 0.990, 0.710-1.237 g/cm(2), p:n.s) , whereas bone mineral density decreased significantly in nine patient s who received placebo (0.984, 0.912-1.374 vs 0.914, 0.781-1.006 g/cm( 2), p<0.05). One patient who had received placebo developed a new vert ebral fracture within 6 months after the end of the trial. This study indicates that cyclosporin A increases the biochemical parameters of b one remodeling, and prevents bone loss in patients with primary biliar y cirrhosis. (C) Journal of Hepatology.