Long-term impact of primary hyperparathyroidism on bone density in the elderly

描述（由申请人提供）：原发性甲状旁腺功能亢进（PHPT）是一种钙代谢疾病，影响1.5%的美国老年人，并可能增加骨折风险。 关于PHPT对骨矿物质密度（BMD）的长期影响的数据有限。 我们与南加州凯萨医疗机构合作，通过电子实验室筛查确定了3388例PHPT患者。 这些患者大多数是老年人，四分之三没有接受过手术治疗。 我们曾报道老年患者不太可能接受PHPT手术，而且老年患者的手术往往不成功。 因此，了解这种疾病的自然史和药物治疗对骨骼健康的影响至关重要，以便优化旨在降低老年人骨折风险的干预措施。我们建议在这个大的PHPT患者队列中检查BMD的长期趋势，同时评估药物治疗的疗效。 我们假设，如果观察≥ 10年而不手术，PHPT会导致骨丢失加速，药物治疗和维生素D充足可减轻不良骨骼影响。 种族多样的人口和先进的信息学结构的凯撒永久使这是唯一的设置，以我们的知识，在这种性质的研究是可行的。 本研究有以下具体目的：1.评估非手术治疗老年PHPT患者在5年、10年和> 10年时的BMD变化。 2.评估抗骨吸收治疗、激素替代治疗和维生素D类似物对这些患者BMD的影响。 3.评估这些患者血清维生素D水平与BMD之间的关系。 本提案的调查结果将用于：a.创建PHPT老年患者的初始队列，并记录BMD数据，前瞻性评价BMD和骨折发生率的进一步变化（立即下一步）。B.联合收割机与PHPT患者肾脏和心血管结局的现有数据相结合，以便对现有药物和手术治疗进行比较有效性研究（立即下一步）。 C.通过现有的Kaiser Permanente电子病历，制定卫生系统干预措施，以降低PHPT老年患者的骨折风险（长期目标）。 这些研究将通过检查在人口统计学和社会经济学上代表较大美国人口的队列，首次大规模表征PHPT在老年人骨骼健康方面的自然史。它们还将填补有关医学疗法功效的关键知识空白。高效能分析提供的连续性结果将指导未来关于PHPT管理的最佳临床实践的医疗保健政策。

DESCRIPTION (provided by applicant): Primary hyperparathyroidism (PHPT), a disease of calcium metabolism, affects 1.5% of older Americans and may increase fracture risk. Limited data are available regarding the long-term effect of PHPT on bone mineral density (BMD). In collaboration with Kaiser Permanente Southern California, we have identified 3388 patients with PHPT using electronic laboratory screening. Most of these patients are elderly, and three-fourths have not been treated surgically. We have reported that elderly patients are unlikely to undergo surgery for PHPT, and furthermore, that surgery is frequently unsuccessful in the elderly. Hence it is critical to understand the natural history of this disease and the effect of medical therapies on skeletal health in order to optimize interventions aimed at reducing fracture risk in the elderly. We propose to examine long-term trends in BMD in this large cohort of patients with PHPT, while concurrently assessing the efficacy of medical therapies. We hypothesize that PHPT leads to accelerated bone loss if observed for =10 years without surgery, and that medical therapies and vitamin D adequacy mitigate adverse skeletal effects. The ethnically diverse population and the advanced informatics structure of Kaiser Permanente make this the only setting to our knowledge in which a study of this nature is feasible. This study has the following specific aims: 1. Assess changes in BMD at 5, 10, and >10 years in elderly patients with PHPT managed non-surgically. 2. Assess the effect of antiresorptive therapy, hormone replacement therapy, and vitamin D analogues on BMD in these patients. 3. Assess the relationship between serum vitamin D levels and BMD in these patients. The findings from this proposal will be used to: a. Create an inception cohort of elderly patients with PHPT and recorded BMD data that will be evaluated prospectively for further changes in BMD and fracture incidence (Immediate next step). b. Combine with existing data on renal and cardiovascular outcomes in patients with PHPT to enable comparative effectiveness research on existing medical and surgical therapies (Immediate next step). c. Develop health systems interventions, effected through the existing Kaiser Permanente electronic medical record, to decrease fracture risk in elderly patients with PHPT (Long-term goal). These studies will provide the first large-scale characterization of the natural history of PHPT as regards skeletal health in the elderly, by examining a cohort demographically and socioeconomically representative of the larger U.S. population. They will also fill a critical knowledge gap regarding the efficacy of medical therapies. Definitive findings provided the highly-powered analyses will guide future health care policy regarding best clinical practice in the management of PHPT.