The impact of glomerular disorders on bone quality and strength
肾小球疾病对骨质量和强度的影响
基本信息
- 批准号:10226160
- 负责人:
- 金额:$ 66.92万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2018
- 资助国家:美国
- 起止时间:2018-09-21 至 2023-07-31
- 项目状态:已结题
- 来源:
- 关键词:18 year old3-DimensionalAcademic Medical CentersAdolescentAdultAgeAge-YearsBiochemicalBiological MarkersBiomechanicsBiopsyBiopsy SpecimenBody mass indexBone DensityBone MatrixBone Mineral ContentsChildChildhoodChronic Kidney FailureClinicalCohort StudiesCompetenceDataDatabasesDefectDevelopmentDevicesDiabetes MellitusDiseaseDoseDual-Energy X-Ray AbsorptiometryElectronic Health RecordExposure toFinite Element AnalysisFractureFundingFutureGenerationsGlucocorticoidsHealthHealth systemHip FracturesHip region structureImpairmentInflammationInflammatoryInfrastructureIntervention TrialKnowledgeLabelLongitudinal StudiesMeasuresMechanicsMetabolismMethodsMineralsMorbidity - disease rateMulti-Institutional Clinical TrialMulticenter StudiesNephrotic SyndromeNeptuneOsteitisOsteomalaciaOutcomeParticipantPathogenesisPathogenicityPatientsPediatric HospitalsPennsylvaniaPeripheralPharmaceutical PreparationsPhiladelphiaPrevention strategyPropertyProspective StudiesProspective cohort studyProteinuriaRaceRadialRaman Spectrum AnalysisRecording of previous eventsRenal OsteodystrophyRenal functionRenal glomerular diseaseReportingResolutionResourcesRiskRisk FactorsSeminalSeveritiesSeverity of illnessSkeletonSpectrum AnalysisSpinal FracturesTetracyclinesTissuesUnited States National Institutes of HealthUniversitiesUrineVertebral columnVitamin DWorkX-Ray Computed Tomographybasebonebone healthbone imagingbone lossbone massbone qualitybone strengthbone turnovercohortfracture riskimmunomodulatory therapiesinsightmechanical propertiesmicroCTmineralizationmodifiable risknanoindentationpopulation basedprospectivesexskeletaltibiayoung adult
项目摘要
PROJECT SUMMARY
Children and adolescents with glomerular disease have unique and potentially modifiable risk factors for
compromised bone health, but our current understanding of skeletal fragility in glomerular disease is lacking. In
the first large population-based cohort study, we recently found that primary glomerular disease was
independently associated with a >45% increased risk of incident spine and hip fracture, and that hip fracture risk
was >1.5-fold greater in patients younger vs. older than 40 years of age. Mechanisms that drive increased
fracture risk in glomerular disease are not clear but likely multifactorial. Our prior work in the Neptune cohort
demonstrated that glomerular disease is associated with disturbances in vitamin D and mineral metabolism, and
patients with glomerular disease are also exposed to medications which may negatively impact bone health.
Identifying modifiable factors that compromise bone strength will facilitate the development of strategies to
reduce fractures and other skeletal complications across the lifecourse. The primary objectives of this study are
to: (1) determine the impact of glomerular disease on bone strength and (2) investigate the pathophysiologic
underpinnings of impaired bone strength in glomerular disease. The proposed multi-center study will leverage
the infrastructure of the NIH-funded CureGN prospective cohort study and the resources of two health systems
[Children's Hospital of Philadelphia (CHOP)/University of Pennsylvania (Penn) and Columbia University Medical
Center] with expertise in state-of-the-art high-resolution bone imaging and biopsy methods, to conduct the first
prospective, longitudinal study to assess determinants of impaired bone quality and strength in glomerular
disease. 150 CureGN participants (100 adults/50 children) and 120 age-, sex-, race-, and body mass index-
matched healthy reference participants will be evaluated at baseline and 12 months. The new 2nd generation
high-resolution peripheral quantitative computed tomography (HR-pQCT) device will be used to assess bone
microarchitecture and generate micro-finite element analysis (µFEA) estimates of bone strength. We will also
determine the DXA measures of areal BMD and bone mineral content (whole body, spine, hip and radius) that
reflect bone deficits captured by HR-pQCT. Tetracycline double labeled transiliac crest bone biopsy specimens
will be collected from a subset of 40 adult CureGN participants and analyzed by 2D histomorphometry; by
microCT for 3D cortical and trabecular microarchitecture and estimated strength by finite element analysis; and
by Nanoindentation/Raman spectroscopy for bone mechanical and matrix-level characterization. Concurrent
clinical and biochemical profiling will allow for assessment of predictors of prospective changes in biomechanical
competence and cortical and trabecular microarchitecture by HR-pQCT as well as tissue-level bone matrix and
mechanical properties. The results of this study will serve specifically to inform future multicenter clinical trials of
interventions to mitigate the effects of glomerular disease on bone health and fracture risk in children and adults
with glomerular disease.
项目概要
患有肾小球疾病的儿童和青少年具有独特且潜在可改变的危险因素
骨骼健康受到损害,但我们目前对肾小球疾病中的骨骼脆弱性缺乏了解。在
在第一个基于人群的大型队列研究中,我们最近发现原发性肾小球疾病是
与发生脊柱和髋部骨折的风险增加 >45% 独立相关,并且髋部骨折风险增加
与 40 岁以上患者相比,年轻患者的患病率高出 1.5 倍以上。驱动机制增加
肾小球疾病中的骨折风险尚不清楚,但可能是多因素造成的。我们之前在海王星队列中的工作
证明肾小球疾病与维生素 D 和矿物质代谢紊乱有关,并且
肾小球疾病患者还会接触可能对骨骼健康产生负面影响的药物。
识别损害骨强度的可改变因素将有助于制定策略
减少整个生命过程中的骨折和其他骨骼并发症。本研究的主要目标是
目的:(1) 确定肾小球疾病对骨强度的影响;(2) 研究肾小球疾病的病理生理学
肾小球疾病中骨强度受损的基础。拟议的多中心研究将利用
NIH 资助的 CureGN 前瞻性队列研究的基础设施和两个卫生系统的资源
[费城儿童医院 (CHOP)/宾夕法尼亚大学 (Penn) 和哥伦比亚大学医学院
中心] 拥有最先进的高分辨率骨成像和活检方法的专业知识,首次进行
评估肾小球骨质量和强度受损的决定因素的前瞻性纵向研究
疾病。 150 名 CureGN 参与者(100 名成人/50 名儿童)和 120 名年龄、性别、种族和体重指数 -
将在基线和 12 个月时对匹配的健康参考参与者进行评估。新2代
高分辨率外周定量计算机断层扫描 (HR-pQCT) 设备将用于评估骨骼
微架构并生成骨强度的微有限元分析 (µFEA) 估计值。我们还将
确定 DXA 面积 BMD 和骨矿物质含量(全身、脊柱、髋部和桡骨)测量值,
反映 HR-pQCT 捕获的骨缺损。四环素双标记经髂嵴骨活检标本
将从 40 名成年 CureGN 参与者的子集中收集并通过 2D 组织形态计量学进行分析;经过
用于 3D 皮质和小梁微结构的 microCT,并通过有限元分析估计强度;和
通过纳米压痕/拉曼光谱进行骨机械和基质水平表征。并发
临床和生化分析将允许评估生物力学预期变化的预测因素
通过 HR-pQCT 以及组织水平骨基质和
机械性能。这项研究的结果将专门为未来的多中心临床试验提供信息
减轻肾小球疾病对儿童和成人骨骼健康和骨折风险影响的干预措施
患有肾小球疾病。
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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Michelle Denburg其他文献
Michelle Denburg的其他文献
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{{ truncateString('Michelle Denburg', 18)}}的其他基金
Mentoring of Early Career Researchers from Diverse Backgrounds
指导来自不同背景的早期职业研究人员
- 批准号:
10797793 - 财政年份:2023
- 资助金额:
$ 66.92万 - 项目类别:
Evaluation of the gut-kidney axis in kidney stone disease
肾结石疾病中肠-肾轴的评估
- 批准号:
9802990 - 财政年份:2019
- 资助金额:
$ 66.92万 - 项目类别:
Evaluation of the gut-kidney axis in kidney stone disease
肾结石疾病中肠-肾轴的评估
- 批准号:
10133067 - 财政年份:2019
- 资助金额:
$ 66.92万 - 项目类别:
Evaluation of the gut-kidney axis in kidney stone disease
肾结石疾病中肠-肾轴的评估
- 批准号:
10385846 - 财政年份:2019
- 资助金额:
$ 66.92万 - 项目类别:
The impact of glomerular disorders on bone quality and strength
肾小球疾病对骨质量和强度的影响
- 批准号:
10452536 - 财政年份:2018
- 资助金额:
$ 66.92万 - 项目类别:
The impact of glomerular disorders on bone quality and strength
肾小球疾病对骨质量和强度的影响
- 批准号:
9789870 - 财政年份:2018
- 资助金额:
$ 66.92万 - 项目类别:
CHOP Pediatric Center of Excellence in Nephrology
CHOP 儿科肾病卓越中心
- 批准号:
10705295 - 财政年份:2017
- 资助金额:
$ 66.92万 - 项目类别:
CHOP Pediatric Center of Excellence in Nephrology
CHOP 儿科肾病卓越中心
- 批准号:
10529731 - 财政年份:2017
- 资助金额:
$ 66.92万 - 项目类别:
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