CHARACTERIZATION OF HEPARIN-INDUCED OSTEOPENIA IN RATS

Heparin has been known to induce osteopenia, but its precise mechanism of action is unknown. In the present study, we examined the effect of heparin on the rat femur using single photon absorptiometry and chara cterized the osteopenia biochemically and pharmacologically. Daily hep arin injection dose dependently induced osteopenia in rats. Significan t bone loss was observed from 2 weeks after starting heparin treatment (2000 U/kg . day) and peaked at 4 weeks. Serum PTH levels were signif icantly elevated from 1 week onward after starting heparin treatment, whereas no significant changes were seen in serum total calcium or ion ized calcium levels. A bone resorption inhibitor, FR78844 (a bisphosph onate compound), significantly attenuated the heparin-induced osteopen ia, as did 1alpha-hydroxyvitamin D3; with the latter, the effective do se was 10 times lower than that needed for a similar effect against im mobilization and ovariectomy-induced osteopenia, suggesting an up-regu lation of 1alpha,25-dihydroxyvitamin D3 receptors in the heparin-treat ed rats. This speculation was supported by the finding that serum la,2 5-dihydroxyvitamin D levels were significantly decreased by 54% in the heparin-treated rats compared to those in normal rats. These results suggest that the enhanced bone resorption by high PTH blood levels and the reduction of 1alpha,25-dihydroxyvitamin D are involved in the pat hogenesis of heparin-induced osteopenia.