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Development of the resorption of bone restrainer aiming at clinical application for the child steroid-related jawbone osteoporosis

针对儿童类固醇相关性颌骨骨质疏松症临床应用的骨吸收限制器的研制

基本信息

批准号：
20592410
负责人：
MAKI Kenshi
金额：
$ 2.58万
依托单位：
Kyushu Dental College
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2008
资助国家：
日本
起止时间：
2008 至 2010
项目状态：
已结题

项目摘要

Gluocorticoids are used to treat various disease, such as severe asthma ,rheumatioid arthritis, and chronic renal disease,but the incidence rates. But the incidence rate of glucocorticoid-induced osteoporosis is approximately 50% in patients treated for 6 months or longer. In children,not only osteoporosis but also growth retaradation occurred with choronic glucocorticoid therapy.However, little is known about the bone metabolism and bone architecture of the mandible with GC induced osteoporosis in children and adolescens. Bisphosphanate which are widely use to manage adluts with osteoporosis are divided into 2 classes according to their chemical structure and mechanism of action. The nitrogen-containing bisphosphonates ,such as risedoronate ,are markedly more potent inhibitors of osteoclastic bone resorption than nonnitrogen-containing bisphosphonates ,such as etidronate and clodronate. Hover,the effctts of nitrogen-containing bisphosphonates on bone structure and bone formation of the mandible in cases of established GC induced osteoporosis during the growth syage are unknown.The aim of the present study was to estimate the effects of the tibia and mandible in growing rats treaed with t glucocorticoid (GC) 5-wwk-old male Wistar rats were given oral risedoronate were given oral in dose of (saline), 0.5, or 1.0mg/kg/day for 4 weeks following administration of oral predonisolone in dose of 30mg/kg/2days for 6 weeks.In trabecular bone, risedronate improved the GC induced decreases in bone cross-sectional area and bone mineral content. Risedoronate increased bone density and also formed formed dense bone microarchitetecture by reducing in bone turn over rate. In cortical bone ,risedronate improved GC induced decreases in bone cross sectional area and bone mineral content.

糖皮质激素用于治疗各种疾病，如严重哮喘、类风湿性关节炎和慢性肾脏疾病，但发病率高。但在治疗6个月或更长时间的患者中，糖皮质激素所致骨质疏松症的发生率约为50%。在儿童中，慢性糖皮质激素治疗不仅发生骨质疏松症，而且发生生长迟缓。然而，对于儿童和青少年GC性骨质疏松患者下颌骨的骨代谢和骨结构知之甚少。双磷酸盐广泛用于治疗成人骨质疏松症，根据其化学结构和作用机制可分为两类。含氮双膦酸盐，如雷塞多酸盐，比不含氮的双膦酸盐，如地替膦酸盐和氯膦酸盐，对破骨细胞骨吸收的抑制作用明显更有效。然而，含氮双膦酸盐对生长阶段已确定的GC性骨质疏松患者下颌骨骨结构和骨形成的影响尚不清楚。本研究的目的是评估5周龄雄性Wistar大鼠经糖皮质激素（GC）治疗后对胫骨和下颌骨的影响，在给予口服强的松龙（30mg/kg/2天）后，分别以（生理盐水）、0.5或1.0mg/kg/天口服利塞多酸酯4周。在小梁骨中，利塞膦酸钠改善了GC诱导的骨截面积和骨矿物质含量的减少。立塞多酸增加了骨密度，并通过降低骨周转率形成了致密的骨微结构。在皮质骨中，利塞膦酸酯改善GC诱导骨横截面积和骨矿物质含量降低。