PATHOPHYSIOLOGY OF SENILE TYPE 11 OSTEOPOROSIS

有证据表明，衰老和更年期都会导致骨质流失。 取自股骨近端。更年期成分被更清楚地定义， 它造成了大约20%的股骨颈寿命损失， 组件大约在7年内发生。 绝经前股骨颈丢失的原因根本不清楚， 但这相当于一生损失的30%。另外50%的股骨颈丢失 发生在60岁到90岁之间。我们的假设是吸收不良 钙，开始于60年代中期，与次要的 甲状旁腺功能亢进症起致病作用。 这些研究的目的是确定吸收不良的原因。 在开始临床试验前随机抽取100名妇女中的一组 审判。我们将测量钙吸收、维生素D代谢物和 十二指肠标本测定1，25二羟基维生素D受体浓度。一个 “老化的肠道”与“肾脏”的初步分类可以用以下方法进行 发现低受体浓度但正常血清1，25(OH)2D。 前者与后者相反。然而，在“肾”组中， 1，25(OH)2D存在原发或继发下降的可能性 制作。为了将小学和中学分开，受试者将经历 甲状旁腺素的动态刺激，可能是老化的肾脏(原发) 生成的1，25(OH)2D比仲基少。 经过一年的治疗后，亚组(每组25人)将拥有所有 重复试验和雌激素或1α-羟基维生素D2对小鼠的影响 随后是受体、维生素D水平和吸收情况。 由于继发性甲状旁腺功能亢进症增加骨转换，血清 将使用骨钙素、尿羟脯氨酸和吡啶交联物 来跟踪营业额。骨吸收与骨转换的相关性研究 由125名受试者组成的安慰剂组将接受检查，并观察其效果 改善骨骼对钙的吸收(在1α-OH-D2治疗后) 营业额。雌激素对骨吸收可能有独立作用 而不考虑吸收的变化。 这些研究可以确定哪些老年受试者将受益 从雌激素或维生素D类似物中选择性地提供一种合理的 为治疗骨质流失奠定了基础。

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.