Hip Fracture Pathology in Chronic Kidney Disease
慢性肾脏病髋部骨折病理学
基本信息
- 批准号:10335225
- 负责人:
- 金额:$ 61.78万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 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:
- 关键词:AgeAge-Related OsteoporosisAlternative TherapiesAnatomyBiological MarkersBiologyBiopsyBone DensityBone DiseasesBone TissueBone structureChronic Kidney FailureClinicalComplexDataDiabetes MellitusDialysis patientsDiseaseElderlyEvaluationFDA approvedFractureFrequenciesFunctional disorderFutureGeneral PopulationGoldHip FracturesHip region structureHyperparathyroidismIndividualKidneyLesionLow PrevalenceMeasuresMedical centerMetabolic Bone DiseasesMethodsMorbidity - disease rateMulticenter StudiesOperative Surgical ProceduresPTH geneParticipantPathologyPatient-Focused OutcomesPatientsPharmaceutical PreparationsPrevalenceProspective StudiesRisk FactorsSerumSiteSpecialized CenterSpecificitySpecimenTestingTimeVisionWomanbasebiomarker panelbisphosphonatebonebone metabolismbone turnoverclinically relevantcohortcommunity livingconventional therapycostexperiencefibroblast growth factor 23fracture riskhigh riskhip boneimaging modalityimprovedkidney imagingmineralizationmortalityolder womenosteoporosis with pathological fracturepatient subsetspreventrepairedspecific biomarkers
项目摘要
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,并与发病率和死亡率密切相关。患者
慢性肾脏病(CKD)、骨折风险和骨折后死亡率是一般情况的两倍。
人群;透析患者发生髋部骨折的年龄比其年龄匹配的患者小10-15岁
同行
CKD中髋部骨折的治疗特别具有挑战性,因为这些患者具有多种不同的
骨疾病的病理,不同的病理有不同的治疗方法。CKD患者可以
患有与非CKD患者相似的年龄相关性骨质疏松症,但也可能患有CKD相关的代谢性骨
反映低转换疾病、高转换疾病(通常由甲状旁腺功能亢进引起)或
混合病变,即使在相同水平的骨矿物质密度。CKD患者的低骨转换似乎
频率增加,并且是有问题的,因为大多数标准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,
而不是抑制骨转换。因此,了解CKD患者的骨转换尤为及时,
并最终看看这些信息是否可以指导临床医生改善患者的治疗效果。
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
由于只有少数几个专门的中心执行它们,所以不能广泛获得并且很少获得。当
然而,骨组织形态计量学通常在髂嵴进行评价,
包括髋部在内的其他骨部位的骨转换。为了更好地了解髋关节的骨转换,
我们建议使用CKD患者髋部骨折手术修复过程中获取的髋骨组织进行组织形态计量学研究,
因为它可以传递关于骨代谢和结构的相关信息。具体来说,我们将确定
CKD髋部骨折患者低骨转换的患病率和危险因素(目的1)。
如果不进行活检,临床医生识别低骨转换患者的能力有限。
我们的初步数据表明,生物标志物有希望识别低骨转换,具有高特异性,
CKD患者。然而,目前还不存在定义髋关节低骨转换的最佳生物标志物组。
我们建议根据髋骨活检的结果,
组织形态计量学表明骨转换率低(目的2)。我们最近的发现表明,使用血清
基于髂嵴组织形态计量学的对低骨转换特异的生物标志物可应用于
社区生活的CKD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志物应用于一组CKD女性,
表征骨矿物质密度和骨折(在骨质疏松性骨折研究中),以确定髋关节
骨折风险在这个子集的个人(目标3)。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Jan Marie Hughes-Austin其他文献
Jan Marie Hughes-Austin的其他文献
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{{ truncateString('Jan Marie Hughes-Austin', 18)}}的其他基金
Hip Fracture Pathology in Chronic Kidney Disease
慢性肾脏病髋部骨折病理学
- 批准号:
10540770 - 财政年份:2020
- 资助金额:
$ 61.78万 - 项目类别:
Hip Fracture Pathology in Chronic Kidney Disease
慢性肾脏病髋部骨折病理学
- 批准号:
10116247 - 财政年份:2020
- 资助金额:
$ 61.78万 - 项目类别:
Antibodies to Citrullinated Protein Antigens, CVD and Bone Disease in MESA
MESA 中瓜氨酸蛋白抗原、CVD 和骨病的抗体
- 批准号:
8890626 - 财政年份:2015
- 资助金额:
$ 61.78万 - 项目类别:
Antibodies to Citrullinated Protein Antigens, CVD and Bone Disease in MESA
MESA 中瓜氨酸蛋白抗原、CVD 和骨病的抗体
- 批准号:
9283594 - 财政年份:2015
- 资助金额:
$ 61.78万 - 项目类别:
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