HYPONATREMIA-INDUCED OSTEOPOROSIS

描述（由申请人提供）： 骨质疏松症以及由此产生的骨质疏松性骨折是美国的主要健康问题。众所周知，年龄和性腺激素缺乏是骨质疏松症的主要危险因素，而骨质疏松症的其他原因也越来越多地被认为是加速骨质流失和增加骨折发生率的原因。最近的研究发现，在无症状的骨质疏松症女性中，骨质疏松症的次要原因发生率很高：药物使用导致53%的骨质流失，44%的激素和代谢异常，以及18%的胃肠道慢性疾病，慢性阻塞性肺病，器官移植，自身免疫性疾病，遗传性疾病，骨髓和肿瘤疾病。因此，从预防和治疗的角度来看，识别导致骨质疏松症的新因素是重要的。在考虑骨丢失的其他潜在原因时，由于抗利尿激素分泌不当综合征（SIADH）导致慢性低钠血症患者发生不明原因的骨质疏松症的临床病例促使我们将其作为加速骨丢失的另一个潜在原因进行研究。使用本实验室开发的慢性稳定性低钠血症动物模型，本资助申请中提出的初步研究证实慢性低钠血症与年轻和老年大鼠的严重骨质疏松症相关，并表明低钠水平对刺激破骨细胞介导的骨吸收的直接影响。此外，第三次全国健康和营养检查调查（NHANES III）的人类数据分析显示，与血清钠水平正常的人相比，美国50岁以下患有低钠血症的成年人髋部骨质疏松症的比值比显着增加。鉴于老年患者中低钠血症的报告患病率较高（7-35%），加上最近发现步态不稳与无症状低钠血症患者的福尔斯跌倒之间存在相关性，该脆弱老年人群中加速骨质疏松症的任何额外风险增加都将引起高度关注。因此，这些研究将直接解决这一假设，即低钠血症是以前未被认识到的骨质疏松症的原因，是一个促成因素，高发病率和死亡率的骨疾病和骨折在我们的老年人population.Hyponatremia，或低钠浓度的血液中，发生在7-35%的老年患者。最近，这种疾病已被证明会导致步态不稳和增加的发病率福尔斯的患者。我们的初步研究表明，低钠血症也会导致动物显著的骨质流失，并与人类骨质疏松症风险增加独立相关。本资助申请中的研究将确定低钠血症在多大程度上是骨质疏松症的一个以前未被认识到的原因，这可能导致我们脆弱的老年人群中骨骼疾病和骨折的高发病率和死亡率。

DESCRIPTION (provided by applicant): Osteoporosis, and resulting osteoporotic fractures, are major health problems in the United States. Whereas age and gonadal hormone deficiency are well known to be major risk factors for osteoporosis, other causes of osteoporosis are increasingly recognized as contributing to accelerated bone loss and increased fracture incidence. Recent studies have found a high frequency of secondary causes of osteoporosis in asymptomatic women with osteoporosis: medication use contributed to bone loss in 53%, hormonal and metabolic abnormalities in 44%, and chronic diseases of the gastrointestinal tract, chronic obstructive pulmonary disease, organ transplantation, autoimmune diseases, genetic diseases, and marrow-based and neoplastic disorders in 18% in aggregate. Consequently, recognition of novel factors leading to osteoporosis is important from both a preventative and a therapeutic perspective. In considering other potential causes of bone loss, clinical cases of unexplained osteoporosis in patients with chronic hyponatremia due to the syndrome of inappropriate antidiuretic hormone secretion (SIADH) prompted us to examine this as another potential cause of accelerated bone loss. Using an animal model of chronic stable hyponatremia developed in this laboratory, the preliminary studies presented in this grant application verify that chronic hyponatremia is associated with severe osteoporosis in both young and aged rats, and suggest a direct effect of low sodium levels to stimulate osteoclast-mediated bone resorption. Moreover, analysis of human data from the Third National Health and Nutrition Examination Survey (NHANES III) showed a significantly increased odds ratio for osteoporosis in the hip among U.S. adults e50 years with hyponatremia compared to those with normal serum sodium levels. In view of the high reported prevalence of hyponatremia in geriatric patients (7-35%) coupled with a recently discovered association between gait instability and falls in patients with even asymptomatic hyponatremia, any additional increased risk of accelerated osteoporosis in this vulnerable aged population would be of great concern. These studies will therefore directly address the hypothesis that hyponatremia represents a previously unrecognized cause of osteoporosis, and is a contributing factor to the high morbidity and mortality from bone disease and fracture in our elderly population.Hyponatremia, or low sodium concentrations in the blood, occurs in 7-35% of geriatric patients. Recently, this disorder has been shown to cause gait instability and an increased incidence of falls in patients. Our preliminary studies have shown that hyponatremia also causes significant bone loss in animals, and is independently associated with an increased risk of osteoporosis in humans. The studies in this grant application will ascertain to what degree hyponatremia is a previously unrecognized cause of osteoporosis, which may contribute to the high morbidity and mortality from bone disease and fracture in our vulnerable elderly population.