Leveraging modeling-based bone formation for osteoporosis treatment
利用基于模型的骨形成治疗骨质疏松症
基本信息
- 批准号:10366040
- 负责人:
- 金额:$ 42.04万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-03-05 至 2026-01-31
- 项目状态:未结题
- 来源:
- 关键词:AdultAnabolic AgentsAntibodiesBone ResorptionBone SurfaceBone TissueBone remodelingBone structureChronicClinicalCollagenCoupledDataDepositionDevelopmentHardnessHeterogeneityImageImage AnalysisKnowledgeLengthLifeLongevityMechanicsMineralsModelingModulusOsteoblastsOsteoclastsOsteogenesisOsteoporosisPTH genePeriodicityPredispositionRattusRegimenResearch Project GrantsResistanceSequential TreatmentSiteSkeletonStructureStructure-Activity RelationshipTestingTherapeuticTimeTissuesTreatment EfficacyTreatment ProtocolsWithdrawalbasebonebone lossbone massbone strengthdesignimaging platformimprovedinnovationinsightmechanical propertiesmineralizationnovelnovel therapeuticsparathyroid hormone-related proteinrecruitregenerativeresponsestandard caretreatment durationtreatment effecttreatment optimizationtreatment strategy
项目摘要
Project Summary
The healthy skeleton continuously renews itself throughout the lifespan via closely coupled bone resorption
and remodeling-based bone formation. In contrast, modeling-based bone formation, i.e., de novo bone
formation without prior activation of bone resorption, is less commonly found in the adult skeleton, but has
been identified as an important mechanism by which anabolic agents for osteoporosis, e.g., intermittent
parathyroid hormone (PTH) and PTH related peptide (PTHrP), and sclerostin antibody (Scl-Ab), rapidly elicit
new bone formation. By developing a novel imaging platform that enables reliable identification of MBF and
RBF and subsequent tissue-level mechanical testing in adult rat bone, we discovered that MBF responds
faster than RBF to anabolic treatments. Moreover, bone tissue resulting from MBF has a greater resistance to
anabolic treatment withdrawal-induced bone loss and increased heterogeneity of elastic modulus compared to
pre-existing bone and bone tissue resulting from RBF. These exciting preliminary data provide a strong
scientific premise to support our central hypothesis that MBF is a highly efficient regenerative mechanism that
leads to sustainable therapeutic benefits on bone tissue quantity and quality, and whole bone strength.
Furthermore, our data suggest that, upon early withdrawal from anabolic treatment, ongoing bone formation
continues at MBF sites, forming an “anabolic window” that retains the treatment effect; In contrast, the majority
of bone tissue formed at RBF sites were resorbed following treatment withdrawal. Therefore, we propose that a
cyclic and sequential treatment regimen with alternating anabolic and anti-resorptive treatments will lead to
increased mineral deposition and number of MBF, improved retention of bone tissue at RBF and quiescent
bone surface, and improved tissue heterogeneity and whole bone strength. The overall objective of this study
is to elucidate the cellular mechanisms (Aim 1a) and mechanical consequences (Aim 2a) of MBF and RBF,
and to evaluate the new treatment regimen which leverages MBF to improve and extend treatment efficacy
(Aim 2a and 2b) using a rat model. By combining our innovative imaging and image analyses with tissue-level
mechanical testing approaches, this proposed research project will fill the critical knowledge gap of long-term
mechanical consequences of bone tissue formed through MBF and RBF, and provide important insight for the
clinical design and optimization of treatment strategies that modulate MBF, a highly efficient but often
overlooked regenerative mechanism.
项目总结
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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Xiaowei Sherry Liu其他文献
Xiaowei Sherry Liu的其他文献
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{{ truncateString('Xiaowei Sherry Liu', 18)}}的其他基金
Influence of sex and sex hormones on modeling- and remodeling-based bone formation
性和性激素对基于建模和重塑的骨形成的影响
- 批准号:
10556506 - 财政年份:2022
- 资助金额:
$ 42.04万 - 项目类别:
Leveraging modeling-based bone formation for osteoporosis treatment
利用基于模型的骨形成治疗骨质疏松症
- 批准号:
10553619 - 财政年份:2021
- 资助金额:
$ 42.04万 - 项目类别:
Leveraging modeling-based bone formation for osteoporosis treatment
利用基于模型的骨形成治疗骨质疏松症
- 批准号:
10208066 - 财政年份:2021
- 资助金额:
$ 42.04万 - 项目类别:
CAREER: Temporal Changes In Rat Maternal Bone During Lactation And After Weaning
职业:哺乳期和断奶后大鼠母骨的时间变化
- 批准号:
1653216 - 财政年份:2017
- 资助金额:
$ 42.04万 - 项目类别:
Standard Grant
Effects of reproduction and lactation on postmenopausal bone health.
生殖和哺乳对绝经后骨骼健康的影响。
- 批准号:
9923534 - 财政年份:2017
- 资助金额:
$ 42.04万 - 项目类别:
Effects of reproduction and lactation on postmenopausal bone health.
生殖和哺乳对绝经后骨骼健康的影响。
- 批准号:
9309401 - 财政年份:2017
- 资助金额:
$ 42.04万 - 项目类别:
Roles of Modeling- and Remodeling-based Bone Formation in Determining Trabecular Bone Mechanics at Multiple Length Scales
基于建模和重塑的骨形成在确定多个长度尺度的小梁骨力学中的作用
- 批准号:
1661858 - 财政年份:2017
- 资助金额:
$ 42.04万 - 项目类别:
Standard Grant
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