PATHOPHYSIOLOGY OF SENILE TYPE 11 OSTEOPOROSIS

有证据表明，老化和更年期都有助于骨质流失 从股骨近端 更年期的定义更加明确， 它导致股骨颈约20%的寿命损失， 大约7年内发生的事件。 绝经前股骨颈丢失的原因根本不清楚， 但它代表了生命损失的30%。 其余50%的股骨颈丢失 发生在60到90岁之间。 我们的假设是吸收不良 钙，这开始在六十年代中期，连同中学 甲状旁腺功能亢进起致病作用。 这些研究的目的是确定吸收不良的原因 在开始临床试验之前，随机抽取100名妇女， 审判 我们将测量钙吸收，维生素D代谢产物和 十二指肠样本的1，25二羟基维生素D受体浓度。 一个 “老化肠道”与“肾脏”的初步分类可通过 发现低受体浓度，但正常血清1，25（OH）2D在 前者与后者相反。 然而，在“肾脏”组中， 可能存在原发性或继发性1，25（OH）2D减少 生产 为了区分主要和次要，受试者将接受 动态刺激与PTH，大概老化的肾脏（主要）将 产生的1，25（OH）2D少于第二组。 经过一年的治疗，子集（每组25人）将有所有 重复测试，雌激素或1 α-羟基维生素D2对 受体，维生素D水平和吸收。 由于继发性甲状旁腺功能亢进增加骨转换，血清 将使用骨钙素、尿羟脯氨酸和吡啶交联 跟踪营业额。 骨吸收与骨转换的相关性 将检查安慰剂组的125名受试者，以及 改善骨钙吸收（1 α-OH-D2治疗后） 周转 雌激素可能对骨吸收有独立作用 而不管吸收的变化。 这些研究可以确定老年受试者的子集， 选择性地从雌激素或维生素D类似物，并提供合理的 治疗骨质流失的基础。

There is evidence that both aging and menopause contribute to bone loss from the proximal femur. The menopause component is more clearly defined, it causes about 20% of the lifetime loss in the femoral neck, and that component occurs in about 7 years. The cause of femoral neck loss prior to menopause is not understood at all, but it represents 30% of lifetime loss. The other 50% of femoral neck loss occurs between age 60 and 90 years. Our hypothesis is that malabsorption of calcium, which starts in the mid sixties, together with secondary hyperparathyroidism plays a pathogenic role. The objectives of these studies are to identify the causes of malabsorption of calcium in a random subset of 100 women before starting the clinical trial. We will measure calcium absorption, vitamin D metabolites and duodenal samples for 1,25 dihydroxy vitamin D receptor concentration. An initial classification of 'aging gut' versus 'kidney' could be made by finding low receptor concentration but normal serum 1,25(OH)2D in the former and the opposite in the latter. However, in the 'kidney' group, there is a possibility of a primary or secondary decrease in 1,25(OH)2D production. To separate primary from secondary, subjects will undergo dynamic stimulation with PTH, presumably the aging kidney (primary) will produce less 1,25(OH)2D than the secondary group. After a year on therapy, the subset (25 from each group) will have all tests repeated and the effect of estrogen or 1alphahydroxyvitamin D2 on receptors, vitamin D levels and absorption followed. Because secondary hyperparathyroidism increases bone turnover, serum osteocalcin, urine hydroxyproline and Pyridinium cross links will be used to follow turnover. Correlations between absorption and bone turnover in the placebo group of 125 subjects will be examined, as well as the effect of improved calcium absorption (after 1alpha-OH-D2 therapy) on bone turnover. Estrogen may have an independent action on bone resorption irrespective of changes in absorption. These studies could identify subsets of elderly subjects who would benefit selectively from estrogen or vitamin D analogues and provide a rational basis for the treatment of bone loss.