MANIPULATION OF BONE REMODELING IN AGING

据估计，每年花费的资金超过10亿美元 老年骨质疏松症患者骨折的治疗 与年龄相关的骨质流失。随着老年人的老龄化，这一成本将稳步上升 美国的人口不断增长，除非找到防止 治疗骨质疏松症。该项目旨在制定战略，将 通过操纵骨骼来增加成年狗骨骼的质量 重塑，从而发展预防和/或治疗所需的治疗 人类的骨质疏松症。需要检验的假设是，骨量 成人骨骼可以通过抑制破骨细胞功能来增加 不会抑制成骨细胞功能，也不会改变正常 在成人骨骼的重塑系统中发现的偶联。这个 拟议的研究将确定适当的制剂将增加 激活新的重塑单位和抑制破骨细胞的骨量 骨吸收而不影响偶联和骨形成。也将是 研究了两种序贯治疗方法的疗效。 增加骨量，以及这种骨量增加能否保持下去 六个月或更长时间。活体和死后的骨骼分析 将采用重塑活动和骨量：血清(钙、磷、镁、 碱性磷酸酶、iPTH、ICT、T(3)、T(4))和尿(Ca、P、 羟脯氨酸、肌酸)生物化学，全身~(99)m-二磷酸盐 保留，定量射线照相；光子吸收测定法， 荧光标记肋骨和髂骨活检的组织形态计量学研究 身体X线片和组织形态计量学分析 荧光标记的长骨和椎骨。我们的主要端点是 增加的骨量的测定。此外，我们计划评估 骨组织形态计量学研究期间的骨重建率。 这些研究将进一步提高我们对骨重建的理解。 并建立间歇性而不是连续性 在治疗骨质疏松症方面，治疗将更加有效。

It has been estimated that more than one billion dollars per year is spent on the treatment of fractures in elderly patients who have osteoporosis from age-related bone loss. This cost will elevate steadily as the elderly population of the United States grows and unless means are found to prevent and treat osteoporosis. This project poses to develop strategies that will increase the mass of the adult dog skeleton by manipulating the bone remodeling and thus develop the treatment needed to prevent and/or treat osteoporosis in man. The hypothesis to be tested is that the bone mass of the adult skeleton can be increased by depressing the osteoclast function without depressing osteoblast function, and without altering the normal coupling found in the remodeling system of the adult skeleton. The proposed studies will determine the appropriate agent that will increase bone mass by activating new remodeling units and depressing osteoclastic bone resorption without affecting coupling and bone formation. Also to be studied is the effectiveness of two types of sequential treatment to increase bone mass, and whether this bone mass increase can be maintained for six months or longer. Both in vivo and post-mortem assays for bone remodeling activities and bone mass will be employed: serum (Ca, P, Mg, alkaline phosphatase, iPTH, iCT, T(3), T(4)) and urinary (Ca, P, hydroxyproline, creatinine) biochemistry, whole body Tc-99m-diphosphonate retention, quantitative radiography; photon absorptiometry, histomorphometry of fluorochrome-labeled rib and iliac crest biopsies and post-mortem analyses of radiographs and histomorphometry of fluorochrome-labeled long bones and vertebrae. Our primary endpoint is the determination of increased bone mass. In addition, we plan to evaluate the bone remodeling rate throughout the studies by bone histomorphometry. These studies will further improve our understanding of bone remodeling in the aging skeleton and establish that intermittent rather than continuous therapy will be more effective in the treatment of osteoporosis.