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

描述(申请人提供)：原发性甲状旁腺功能亢进症(PHPT)，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对骨密度(BMD)的长期影响，现有的数据有限。在与南加州Kaiser Permanente的合作下，我们使用电子实验室筛查确定了3388名PHPT患者。这些患者大多是老年人，四分之三的患者没有接受过手术治疗。我们已经报道过，老年患者不太可能接受PHPT手术，此外，老年人的手术经常不成功。因此，了解这种疾病的自然病史和医疗疗法对骨骼健康的影响，以便优化旨在降低老年人骨折风险的干预措施，是至关重要的。我们建议在这一大群PHPT患者中检测骨密度的长期趋势，同时评估药物治疗的效果。我们假设，如果没有手术观察10年，PHPT会导致加速的骨丢失，药物治疗和维生素D充分性可以缓解对骨骼的不利影响。种族多元化的人口和Kaiser Permanente先进的信息学结构使这成为我们所知的唯一可以进行这种性质研究的环境。 本研究有以下具体目的：1.评估非手术治疗的老年PHPT患者5年、10年和10年时骨密度的变化。2.评估抗吸收治疗、激素替代治疗和维生素D类似物对这些患者骨密度的影响。3.探讨这些患者血清维生素D水平与骨密度的关系。 这项建议的结果将被用于：a.建立一个老年PHPT患者的初始队列，并记录BMD数据，这些数据将被前瞻性地评估BMD和骨折发生率的进一步变化(下一步)。B.结合关于PHPT患者肾脏和心血管结局的现有数据，能够对现有的内科和外科治疗方法进行比较有效性研究(下一步)。C.开发通过现有Kaiser Permanente电子病历实施的卫生系统干预措施，以降低PHPT老年患者的骨折风险(长期目标)。这些研究将首次大规模描述PHPT在老年人骨骼健康方面的自然历史，通过检查人口统计学和社会经济方面具有代表性的美国较大人口的队列。它们还将填补关于医疗疗法疗效的关键知识空白。这些强有力的分析提供了明确的结果，将指导未来关于PHPT管理的最佳临床实践的卫生保健政策。

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.