[Effects of bisphosphonates on vitamin A-induced bone resorption in thyroparathyroidectomized rat].
A bone resorption model in which osteoclasts were selectively activated was made by administering vitamin A--a bone resorption agent--to juvenile thyroparathyroidectomized rat. Inhibition of bone resorption by YM-175--a third generation bisphosphonate--was studied using this model based on bone histomorphometry of the proximal part of the tibia and on biochemical data. Six-week-old male SD rats were thyroparathyroidectomized (TPTX). On the 11th day following TPTX they were treated with vitamin A (etretinate). In the calcitonin group, salmon calcitonin or its vehicle was added, and in the bisphosphonate group, YM-175 or its vehicle was added. They were sacrificed on the 21st day following TPTX. Calcitonin was used to confirm its inhibitory activity of bone resorption in this model. Cancellous bone in the epiphysis was subjected to histomorphometry using tetracycline labeling or TRAP staining, and the number of primary trabeculae at the metaphysis was counted to evaluate bone resorption activity. Serum calcium, phosphorus, urinary calcium, phosphorus, pyridinoline and deoxypyridinoline were measured for biochemical analysis. YM-175 did not change any bone formation parameters in the histomorphometry of the epiphysis, while it significantly decreased resorption parameters both histomorphometrically and biochemically. Primary trabeculae at the metaphysis were found to be longer and denser after administration of YM-175. The effect of YM-175 as a bone resorption inhibitor was observed even in a short duration experiment. There was no damage to mineralization, and no inhibiting effect was observed on bone formation. Similar results were observed by calcitonin. YM-175 was concluded to be an inhibitor of bone resorption caused by vitamin A administration.
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M
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Department of Orthopedic Surgery, Akita University School of Medicine, Japan.
D000818:Animals; D001862:Bone Resorption / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D001842:Bone and Bones / Q000378:metabolism / Q000473:pathology; D004164:Diphosphonates / Q000627:therapeutic use*; D004195:Disease Models, Animal; D008297:Male; D016105:Parathyroidectomy; D051381:Rats; D017207:Rats, Sprague-Dawley; D013965:Thyroidectomy; D014801:Vitamin A
D004164:Diphosphonates; D014801:Vitamin A; C071542:cimadronate