HORMONAL REGULATION OF BONE GROWTH IN VIVO

超生理剂量的甲状旁腺素和1，25(OH)2D3已被用于尝试 代谢性骨质疏松症患者骨丢失的逆转 主要影响老年人的疾病。人们对这些生物是如何 荷尔蒙调节骨骼细胞的活动以增加骨量。主要目的是 本研究的目的是研究钙对骨形成的调节作用。 调节完整动物体内的荷尔蒙。 我们已经在4-6周龄的大鼠身上建立了促进骨骼生长的方案 通过给予正常剂量的hPTH 1-34连续12天，并损害 高钙剂量下的矿化和刺激基质形成 1，25(OH)2D3给药18天。我们已经开发出方法来测量 骨量(Ca、Hyp、干重)的变化和股骨远端的变化 骨沉积速率、形成表面和矿化速率 大鼠胫骨干骺端和骨干端。要研究的局部化效应 荷尔蒙对体内骨形成的影响，我们正在开发一种新的方法 使用阿尔茨海默病对成年兔股骨进行动脉内激素注射 渗透性的小泵。血清钙、磷、碱性磷酸酶、尿素的变化 氮和肌酐以及在系统生长中的相关性被测试 伴随着骨骼的变化。数据将按单变量和 多元统计分析。 这些方法将用于确定合成代谢剂量的早期影响。 HPTH1-34对骨形成和骨吸收的影响；以确定是否增加 骨量的增加可能与骨沉积率和/或 形成表面；以确定骨骼上的合成代谢效应是否也可以 将hPTH局部注入股动脉循环所致 可以对局部骨生长因子进行调查，以确定 甲状旁腺激素与1，25(OH)2D3联合应用对骨生长的协同作用 在使用年长雌性大鼠的动物模型中繁殖。我们将继续 1，25(OH)2D3对矿化损伤的研究 如果矿化不足的基质在不再暴露于 1，25(OH)2D3和IF 25(OH)D3或24，25(OH)2D3与 1，25(OH)2D3将刺激受影响基质的矿化或 抑制1，25(OH)2D3诱导的反应。

Supraphysiologic doses of PTH and 1,25(OH)2D3 have been used to attempt reversal of bone loss in patients with osteoporosis, a metabolic bone disease primarily affecting older people. Little is known of how these hormones regulate bone cell activity to increase bone mass. The main aim of this research is to study regulation of bone formation by calcium regulating hormones in intact animals. We have established protocols on rats, 4-6 wks old, to increase bone growth by normocalcemic doses of hPTH 1-34 given for 12 days, and to impair mineralization and stimulate matrix formation by hypercalcemic doses of 1,25(OH)2D3 given for 18 days. We have developed methods to measure the changes in bone mass (Ca, Hyp, dry wt.) of distal femurs and the changes in bone appositional rate and forming surfaces and in mineralization rate in rat tibia metaphysis and diaphysis. To study the localized effect of hormones on bone formation in vivo, we are developing a new method of intra-arterial hormone infusion of a femur in mature rabbits, using Alzet osmotic minipumps. Changes in serum Ca, Pi, alkaline phosphatase, urea nitrogen and creatinine and in systemic growth are tested for correlation with the changes in bone. Data will be evaluated by univariate and multivariate statistical analysis. These methods will be used to determine the early effects of anabolic doses of hPTH 1-34 on bone formation and resorption; to determine if the increase in bone mass can be correlated with increased bone apposition rate and/or forming surfaces; to determine if an anabolic effect on bone can also be induced by local infusion of hPTH into the femoral arterial circulation so that local bone growth factors can be investigated and to determine if the synergistic effect of combined PTH and 1,25(OH)2D3 on bone growth can be reproduced in an animal model using older female rats. We will continue our studies of the impairment of mineralization by 1,25(OH)2D3 to determine if the undermineralized matrix will mineralize when no longer exposed to 1,25(OH)2D3 and if 25(OH)D3 or 24,25(OH)2D3, in combination with 1,25(OH)2D3, will either stimulate mineralization of the affected matrix or inhibit the 1,25(OH)2D3-induced response.