Hip Fracture Pathology in Chronic Kidney Disease

项目总结 髋部骨折很常见，费用很高，而且与发病率和死亡率密切相关。对于患有以下疾病的患者 慢性肾脏疾病(CKD)、骨折风险和骨折后死亡率是一般情况的两倍 人群；透析患者的髋部骨折比年龄匹配的人年轻10-15岁 对口单位。 CKD患者髋部骨折的治疗尤其具有挑战性，因为这些患者有多个不同的 骨病的病理，而不同的病理有不同的治疗方法。慢性肾脏病患者可以 有类似于非CKD患者的年龄相关性骨质疏松症，但也可能有CKD相关代谢骨 反映低周转疾病、高周转疾病(通常由甲状旁腺功能亢进症引起)或 混合性病变，即使在相同的骨矿密度水平。慢性肾脏病患者的低骨转换似乎是 频率增加，这是有问题的，因为大多数标准的抗骨折药物可能会加剧低 周转性骨病。另一方面，现在有几种FDA批准的治疗方法可以刺激， 而不是抑制骨骼的转换。因此，了解CKD患者的骨转换尤为及时， 最终看看这些信息是否可以指导临床医生改善患者的预后。 骨活检和组织形态计量学是确定骨转换的金标准。这些方法 由于只有几个专门的中心提供，因此并不广泛可用，而且很少获得。什么时候 然而，可用的骨组织形态计量学通常在髂骨顶部进行评估，但相关性较差。 在包括髋部在内的其他骨骼部位有骨转换。为了更好地了解髋部的骨骼转换， 我们建议使用在CKD患者髋部骨折手术修复过程中采集的髋骨组织进行组织形态计量学。 因为它可以传递有关骨骼代谢和结构的相关信息。具体来说，我们将确定 CKD髋部骨折患者骨转换低下的患病率和危险因素(目标1)。 如果没有活组织检查，临床医生识别低骨转换患者的能力是有限的。 我们的初步数据表明，生物标记物有望以高特异性识别低骨转换。 CKD患者。然而，目前还不存在定义髋部低骨转换的最佳生物标志物小组。 我们建议开发一个使用血清生物标记物的小组，该小组基于髋骨活检和 组织形态计量学显示骨转换低(目标2)。我们最近的发现表明，使用血清 基于髂骨组织形态计量学的低骨转换特异性生物标志物可应用于 社区生活的慢性肾脏病患者，并提供有关未来骨折风险的重要信息。因此，我们将 将这些基于髋部骨转换的生物标记物应用于一组患有CKD的女性，她们的健康状况良好- 以骨密度和骨折为特征(在骨质疏松性骨折研究中)以确定髋关节 这部分人的骨折风险(目标3)。

PROJECT SUMMARY Hip fractures are common, costly, and strongly associated with morbidity and mortality. For patients with chronic kidney disease (CKD), fracture risk and post-fracture mortality are double what they are in the general population; and dialysis patients sustain hip fractures 10-15 years younger than their age-matched counterparts. Treatment for hip fracture in CKD is particularly challenging because these patients have multiple different pathologies of bone disease, and the distinct pathologies have different treatments. Patients with CKD can have age-related osteoporosis similar to non-CKD patients, but may also have CKD-related metabolic bone disease reflecting low turnover disease, high turnover disease (typically driven by hyperparathyroidism) or mixed lesions, even at the same level of bone mineral density. Low bone turnover in CKD patients appears to be increasing in frequency, and is problematic as most standard anti-fracture medications may exacerbate low turnover bone disease. On the other hand, there are now several FDA approved treatments that stimulate, rather than suppress, bone turnover. Thus, it is particularly timely to understand bone turnover in CKD patients, and ultimately see if this information can guide clinicians to improve patient outcomes. Bone biopsy and histomorphometry are the gold standard for determining bone turnover. These methods are not widely available and are rarely obtained due to only a few specialized centers performing them. When available, however, bone histomorphometry is typically evaluated at the iliac crest, which is poorly correlated with bone turnover at other bone sites including the hip. In order to better understand bone turnover at the hip, we propose histomorphometry using hip bone tissue taken during surgical repair of hip fracture in CKD patients as it may deliver relevant information about bone metabolism and structure. Specifically, we will determine the prevalence and risk factors for low bone turnover in hip fracture patients with CKD (Aim 1). Without biopsy, clinicians are limited in their ability to identify a subset of patients with low bone turnover. Our preliminary data suggest biomarkers hold promise to identify low bone turnover with high specificity in CKD patients. Yet, the optimal biomarker panel to define low bone turnover at the hip does not currently exist. We propose to develop a panel using serum biomarkers based on findings from hip bone biopsy and histomorphometry indicative of low bone turnover (Aim 2). Our recent findings suggest that using serum biomarkers that are specific for low bone turnover based on iliac crest histomorphometry can be applied to community-living individuals with CKD and provide important information on future fracture risk. Thus, we will apply these biomarkers based on bone turnover at the hip to a cohort of women with CKD who are well- characterized for bone mineral density and fractures (in the Study of Osteoporotic Fractures) to determine hip fracture risk in this subset of individuals (Aim 3).