Systemic Bone Loss Following Fracture in Humans

人类骨折后的全身性骨质流失

基本信息

项目摘要

Project Summary/Abstract: The most reliable predictor of fracture risk is a previous fracture at any skeletal site. The etiology of this relationship is not fully known, but one contributing mechanism is that fracture initiates a systemic bone loss response, which increases future fracture risk at all skeletal sites. Our lab has generated multiple preclinical studies characterizing this systemic bone loss response following femur fracture in mice. However, the time course and magnitude of systemic bone loss and recovery in humans has not been investigated, and it is currently unknown if systemic bone loss differentially affects older people compared to young people. To address these knowledge gaps, we will use both standard clinical and cutting-edge high-resolution imaging to characterize the systemic bone loss response following a humerus fracture in human subjects. We hypothesize that post-fracture systemic bone loss: 1) will persist for 6 months or more after a humerus fracture followed by partial recovery, 2) will have a greater effect on trabecular bone than on cortical bone, and 3) will have delayed and diminished recovery in older subjects relative to younger subjects. To investigate these hypotheses, we will first determine the time course and magnitude of systemic bone mineral density (BMD) loss and recovery following humerus fracture in young (20-40 years old) and old (60-80 years old) human patients at axial and appendicular skeletal sites (lumbar spine, bilateral hips, tibiae, and forearms) at baseline, 3, 6, 18, and 36 months post-fracture and compare these patients to non-fractured control subjects. At each time point we will also investigate mechanisms of systemic bone loss by measuring serum biomarkers of bone remodeling and inflammation and tracking patient physical activity using accelerometers. Next, we will determine microstructural and biomechanical changes in the trabecular and cortical compartments during systemic bone loss and recovery following fracture in the same patients and how these differ by age. Using clinical quantitative computed tomography (QCT) and high-resolution peripheral QCT (HR-pQCT) at the ipsilateral and contralateral proximal femur, tibia, and radius, we will measure trabecular and cortical density and microstructure and use finite element analysis to estimate mechanical properties of bone. Altogether, these novel studies will reveal that systemic bone loss and recovery following fracture: 1) occurs in human patients similar to what we have shown in mice, but on a much longer timeline, 2) has differential effects at axial vs. appendicular skeletal sites and in trabecular vs. cortical bone, and 3) affects older people differently than younger people, potentially leaving older subjects with permanent deficits in bone mass and strength. The findings from these studies may ultimately help us identify mechanisms of systemic bone loss following fracture, and will inform therapeutic strategies and establish windows of opportunity for preserving skeletal health of patients after a fracture.
项目摘要/摘要: 骨折风险最可靠的预测指标是任何骨骼部位的既往骨折。造成这种情况的原因 两者之间的关系尚不完全清楚,但其中一个作用机制是骨折引发全身骨丢失。 反应,这增加了所有骨骼部位未来骨折的风险。我们的实验室已经产生了多个临床前 关于小鼠股骨骨折后全身骨丢失反应的研究。然而,时间 人类全身性骨丢失和恢复的过程和程度还没有被研究过,而且 目前尚不清楚与年轻人相比,全身性骨丢失对老年人的影响是否存在差异。致信地址 这些知识空白,我们将使用标准的临床和尖端的高分辨率成像来 描述受试者肱骨骨折后全身骨丢失的反应。我们假设 骨折后的全身性骨丢失:1)在骨折后将持续6个月或更长时间,然后是 部分恢复,2)对骨小梁的影响大于对皮质骨的影响,3)延迟 与年轻受试者相比,年龄较大的受试者恢复较差。为了研究这些假设,我们将 首先确定全身骨密度(BMD)丢失和恢复的时间进程和程度 青年(20-40岁)和老年(60-80岁)患者的肱骨骨折后的轴位和 基线、3、6、18和36个月时的附件骨骼部位(腰椎、双侧髋关节、胫骨和前臂) 并将这些患者与未骨折的对照组进行比较。在每个时间点,我们还将 通过测定血清骨重建生物标志物和骨密度来探讨全身性骨丢失的机制 炎症和使用加速计跟踪患者的体力活动。接下来,我们将确定微观结构 全身性骨丢失和恢复期间骨小梁和皮质室的生物力学变化 相同患者的骨折后情况,以及这些情况如何随年龄变化而变化。临床量化计算的应用 同侧和对侧近端的断层扫描(QCT)和高分辨率外周QCT(HR-pQCT) 股骨、胫骨和桡骨,我们将测量骨小梁和皮质的密度和微结构,并使用有限元 骨的力学性能评估的分析。总而言之,这些新颖的研究将揭示系统性 骨折后的骨丢失和恢复:1)在人类患者中发生的情况与我们在小鼠身上显示的情况类似, 但在更长的时间线上,2)在轴向骨骼部位和附件骨骼部位以及在骨小梁中有不同的影响 与皮质骨相比,3)对老年人的影响与年轻人不同,可能会留下老年人 有永久性的骨量和力量缺陷。这些研究的发现可能最终会帮助我们 确定骨折后全身骨丢失的机制,并将为治疗策略提供信息,并建立 骨折后保持患者骨骼健康的机会之窗。

项目成果

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Blaine A. Christiansen其他文献

Investigating the role of complement 5a in systemic bone loss after myocardial infarction
研究补体5a在心肌梗死后全身性骨丢失中的作用
  • DOI:
    10.1016/j.bone.2025.117543
  • 发表时间:
    2025-09-01
  • 期刊:
  • 影响因子:
    3.600
  • 作者:
    Priscilla M. Tjandra;Sophie V. Orr;Selena K. Lam;Anika D. Kulkarni;Yi-Je Chen;Anna Adhikari;Jill L. Silverman;Crystal M. Ripplinger;Blaine A. Christiansen
  • 通讯作者:
    Blaine A. Christiansen
Justification of Body Mass Index cutoffs for hip and knee joint arthroplasty among California orthopedic surgeons
  • DOI:
    10.1186/s13018-025-05551-3
  • 发表时间:
    2025-01-31
  • 期刊:
  • 影响因子:
    2.800
  • 作者:
    Sophie V. Orr;Gavin C. Pereira;Blaine A. Christiansen
  • 通讯作者:
    Blaine A. Christiansen
648 - Comparison of Compression and Non-Compression Anterior Cruciate Ligament Rupture Models in Mice
  • DOI:
    10.1016/j.joca.2024.02.663
  • 发表时间:
    2024-04-01
  • 期刊:
  • 影响因子:
  • 作者:
    Kei Takahata;Yu-Yang Lin;Benjamin Osipov;Kohei Arakawa;Saaya Enomoto;Blaine A. Christiansen;Takanori Kokubun
  • 通讯作者:
    Takanori Kokubun
Osteocytic oxygen sensing: Distinct impacts of VHL and HIF-2alpha on bone integrity
  • DOI:
    10.1016/j.bone.2024.117339
  • 发表时间:
    2025-03-01
  • 期刊:
  • 影响因子:
  • 作者:
    Sarah V. Mendoza;Kristina V. Wells;Deepa K. Murugesh;Nicholas R. Hum;Aimy Sebastian;Bria M. Gorman;Alice Wong;Benjamin Osipov;Blaine A. Christiansen;Gabriela G. Loots;Alexander G. Robling;Clare E. Yellowley;Damian C. Genetos
  • 通讯作者:
    Damian C. Genetos

Blaine A. Christiansen的其他文献

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{{ truncateString('Blaine A. Christiansen', 18)}}的其他基金

Modification of Post-Traumatic Osteoarthritis Progression with Joint Unloading
通过关节卸载来改变创伤后骨关节炎的进展
  • 批准号:
    10549290
  • 财政年份:
    2020
  • 资助金额:
    $ 79.19万
  • 项目类别:
Modification of Post-Traumatic Osteoarthritis Progression with Joint Unloading
通过关节卸载来改变创伤后骨关节炎的进展
  • 批准号:
    9896699
  • 财政年份:
    2020
  • 资助金额:
    $ 79.19万
  • 项目类别:
Acceleration of Alzheimer’s Disease Pathology Due to Osteoarthritis-Associated Inflammation
骨关节炎相关炎症加速阿尔茨海默病的病理变化
  • 批准号:
    10292125
  • 财政年份:
    2020
  • 资助金额:
    $ 79.19万
  • 项目类别:
Modification of Post-Traumatic Osteoarthritis Progression with Joint Unloading
通过关节卸载来改变创伤后骨关节炎的进展
  • 批准号:
    10320037
  • 财政年份:
    2020
  • 资助金额:
    $ 79.19万
  • 项目类别:
Mechanisms of Systemic Bone Loss Following Femur Fracture in Mice
小鼠股骨骨折后全身性骨丢失的机制
  • 批准号:
    9980294
  • 财政年份:
    2017
  • 资助金额:
    $ 79.19万
  • 项目类别:
Mechanisms of Systemic Bone Loss Following Femur Fracture in Mice
小鼠股骨骨折后全身性骨丢失的机制
  • 批准号:
    10216174
  • 财政年份:
    2017
  • 资助金额:
    $ 79.19万
  • 项目类别:
Mechanisms of Systemic Bone Loss Following Femur Fracture in Mice
小鼠股骨骨折后全身性骨丢失的机制
  • 批准号:
    9291294
  • 财政年份:
    2017
  • 资助金额:
    $ 79.19万
  • 项目类别:
The role of the inflammatory response in bone and cartilage changes following non
非手术后炎症反应在骨和软骨变化中的作用
  • 批准号:
    8280849
  • 财政年份:
    2012
  • 资助金额:
    $ 79.19万
  • 项目类别:
The role of the inflammatory response in bone and cartilage changes following non
非手术后炎症反应在骨和软骨变化中的作用
  • 批准号:
    8918263
  • 财政年份:
    2012
  • 资助金额:
    $ 79.19万
  • 项目类别:
The role of the inflammatory response in bone and cartilage changes following non
非手术后炎症反应在骨和软骨变化中的作用
  • 批准号:
    9116034
  • 财政年份:
    2012
  • 资助金额:
    $ 79.19万
  • 项目类别:

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