Characterization of heparin-induced osteopenia in rats
| Autor: | Takako Yoshino, Nobuaki Takeshita, Seitaro Mutoh, Isamu Yamaguchi |
|---|---|
| Rok vydání: | 1993 |
| Předmět: |
medicine.medical_specialty
Bone disease medicine.drug_class Ovariectomy medicine.medical_treatment Bone resorption Absorptiometry Photon Calcification Physiologic Organ Culture Techniques Endocrinology Calcitriol Internal medicine Animals Medicine Rats Wistar Calcium metabolism Diphosphonates Heparin Hydroxycholecalciferols business.industry Skull Anticoagulant Bisphosphonate Vitamin D Deficiency medicine.disease Effective dose (pharmacology) Rats Osteopenia Bone Diseases Metabolic Parathyroid Hormone Female business medicine.drug |
| Zdroj: | Endocrinology. 133:2743-2748 |
| ISSN: | 1945-7170 0013-7227 |
| DOI: | 10.1210/endo.133.6.8243298 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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