Hip Fracture Pathology in Chronic Kidney Disease

慢性肾脏病髋部骨折病理学

• 批准号: 10116247
• 负责人: Jan Marie Hughes-Austin
• 金额: $ 64.21万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-03-01 至 2024-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10116247
• 关键词: Age; Age-Related Osteoporosis; Alternative Therapies; Anatomy; Biological Markers; Biology; Biopsy; Bone Density; Bone Diseases; Bone Tissue; Bone structure; Chronic Kidney Failure; Clinical; Complex; Data; Diabetes Mellitus; Dialysis patients; Disease; Elderly; Evaluation; FDA approved; Fracture; Frequencies; Functional disorder; Future; General Population; Gold; Hip Fractures; Hip region structure; Hyperparathyroidism; Individual; Kidney; Lesion; Low Prevalence; Measures; Medical center; Metabolic Bone Diseases; Methods; Morbidity - disease rate; Multicenter Studies; Operative Surgical Procedures; PTH gene; Participant; Pathology; Patient-Focused Outcomes; Patients; Pharmaceutical Preparations; Prevalence; Prospective Studies; Risk Factors; Serum; Site; Specialized Center; Specificity; Specimen; Testing; Time; Vision; Woman; base; biomarker panel; bisphosphonate; bone; bone metabolism; bone turnover; clinically relevant; cohort; community living; conventional therapy; cost; experience; fibroblast growth factor 23; fracture risk; high risk; hip bone; imaging modality; improved; kidney imaging; mineralization; mortality; older women; osteoporosis with pathological fracture; patient subsets; prevent; repaired; specific biomarkers

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).

项目摘要 髋部骨折是常见的，昂贵的，并且与发病率和死亡率密切相关。适用于患者 慢性肾脏疾病（CKD），断裂风险和骨折后死亡率是一般情况的两倍 人口;透析患者维持髋部骨折比年龄匹配的年龄小10-15岁 同行。 CKD中髋部骨折的治疗特别具有挑战性，因为这些患者有多个不同 骨病的病理和不同的病理具有不同的治疗方法。患有CKD的患者可以 与年龄相关的骨质疏松症与非CKD患者类似，但也可能具有CKD相关的代谢骨 疾病反映了流动率低的疾病，高离职率疾病（通常由甲状旁腺功能亢进症驱动）或 混合病变，即使在相同水平的骨矿物质密度下也是如此。 CKD患者的骨转换率低似乎 频率增加，并且有问题，因为大多数标准的抗骨折药物可能会加剧较低 离职骨病。另一方面，现在有几种FDA批准的治疗方法可以刺激， 而不是抑制骨骼更新。因此，了解CKD患者的骨转换尤其是及时的， 并最终查看此信息是否可以指导临床医生改善患者的预后。 骨活检和组织形态法是确定骨转换的金标准。这些方法 由于只有少数专业中心执行它们，因此很少获得广泛的可用性，而且很少获得。什么时候 但是，通常在iLiac Crest上评估骨骼组织形态法，该计量学的相关性较差 在包括臀部在内的其他骨骼部位的骨转换。为了更好地理解臀部的骨转换， 我们提出了使用CKD患者的髋部骨折手术修复期间进行的髋骨组织的组织形态计量学 因为它可能会提供有关骨骼代谢和结构的相关信息。具体来说，我们将确定 髋部骨折患者CKD患者骨转换率低的患病率和危险因素（AIM 1）。 在没有活检的情况下，临床医生的识别骨转换率低的患者的子集的能力受到限制。 我们的初步数据表明，生物标志物有望确定低骨转换，并具有很高的特异性 CKD患者。然而，目前尚不存在最佳的生物标志物面板来定义髋关节的低骨转换。 我们建议根据髋骨活检和 组织形态计量法指示低骨转换率（AIM 2）。我们最近的发现表明使用血清 基于iLiac Crest组织形态计量法特定于低骨转换的生物标志物可以应用于 具有CKD的社区生活的人，并提供有关未来骨折风险的重要信息。因此，我们会的 根据臀部的骨转换应用这些生物标志物 骨矿物质密度和裂缝（在骨质疏松性裂缝的研究中）的特征是确定髋关节 该子集中的裂缝风险（AIM 3）。