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 characterized the osteopenia biochemically and pharmacologically. Daily heparin injection dose dependently induced osteopenia in rats. Significant bone loss was observed from 2 weeks after starting heparin treatment (2000 U/kg.day) and peaked at 4 weeks. Serum PTH levels were significantly elevated from 1 week onward after starting heparin treatment, whereas no significant changes were seen in serum total calcium or ionized calcium levels. A bone resorption inhibitor, FR78844 (a bisphosphonate compound), significantly attenuated the heparin-induced osteopenia, as did 1 alpha-hydroxyvitamin D3; with the latter, the effective dose was 10 times lower than that needed for a similar effect against immobilization and ovariectomy-induced osteopenia, suggesting an up-regulation of 1 alpha, 25-dihydroxyvitamin D3 receptors in the heparin-treated rats. This speculation was supported by the finding that serum 1 alpha, 25-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 1 alpha, 25-dihydroxyvitamin D are involved in the pathogenesis of heparin-induced osteopenia.
Mutoh
S
S
Tsukuba Research Laboratories, Fujisawa Pharmaceutical Co. Ltd., Ibaraki, Japan.
Takeshita
N
N
Yoshino
T
T
Yamaguchi
I
I
D015502:Absorptiometry, Photon; D000818:Animals; D001851:Bone Diseases, Metabolic / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D002113:Calcification, Physiologic / Q000187:drug effects; D002117:Calcitriol / Q000097:blood; D004164:Diphosphonates / Q000494:pharmacology; D005260:Female; D006493:Heparin; D006887:Hydroxycholecalciferols / Q000494:pharmacology; D009924:Organ Culture Techniques; D010052:Ovariectomy; D010281:Parathyroid Hormone / Q000097:blood; D051381:Rats; D017208:Rats, Wistar; D012886:Skull / Q000187:drug effects; D014808:Vitamin D Deficiency / Q000097:blood / Q000378:metabolism
D004164:Diphosphonates; D006887:Hydroxycholecalciferols; D010281:Parathyroid Hormone; C084620:FR 78844; D006493:Heparin; D002117:Calcitriol; C008088:alfacalcidol