Aging Leads to a Dysregulation in Mechanically Driven Bone Formation and Resorption
Aging Leads to a Dysregulation in Mechanically Driven Bone Formation and Resorption
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DOI：
10.1002/jbmr.2528
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发表时间：
2015-10-01
影响因子：
6.2
通讯作者：
Checa, Sara
中科院分区：
文献类型：
--
作者：
Razi, Hajar;Birkhold, Annette I.;Checa, Sara
体力活动对维持骨骼质量和结构至关重要，但其效果似乎随着年龄的增长而减弱。为了检验骨对机械应变随年龄增长变得不那么敏感的假设，我们使用了体内/计算机模拟方法。我们研究了成熟和衰老如何影响小鼠2周非侵入性体内控制负荷的骨形成和骨吸收的机械调节。使用纵向显微计算机断层扫描图像的三维体内形态测量评估，我们量化了小鼠胫骨中骨沉积或吸收的部位，以响应受控的体内负荷。我们比较了（重新）建模事件（形成/吸收/静止）在这些网站（使用有限元分析预测）诱导的机械应变。所有年龄组（年轻，成年和老年）的小鼠对负荷的反应是形成增加和吸收减少，特别是在高应变。低应变与成年和老年小鼠无合成代谢反应，而年轻的动物表现出强烈的反应。成年动物表现出明显的应变范围之间的分离，形成和吸收发生，但没有一个中间静止的“懒惰区”。这种应变阈值在老年小鼠中消失，因为机械诱导的（重新）建模变得失调，明显表现为无法抑制吸收或启动形成。与迄今为止普遍认为的相反，衰老并没有改变启动形成或吸收所需的机械阈值，而是模糊了其特异性。这些数据表明，增加体育锻炼的药物策略应考虑骨（重新）建模的机械调节功能障碍，以更有效地对抗年龄相关的骨丢失。(C)2015年美国骨与矿物质研究学会。
Physical activity is essential to maintain skeletal mass and structure, but its effect seems to diminish with age. To test the hypothesis that bone becomes less sensitive to mechanical strain with age, we used a combined in vivo/in silico approach. We investigated how maturation and aging influence the mechanical regulation of bone formation and resorption to 2 weeks of noninvasive in vivo controlled loading in mice. Using 3D in vivo morphometrical assessment of longitudinal microcomputed tomography images, we quantified sites in the mouse tibia where bone was deposited or resorbed in response to controlled in vivo loading. We compared the (re)modeling events (formation/resorption/quiescent) to the mechanical strains induced at these sites (predicted using finite element analysis). Mice of all age groups (young, adult, and elderly) responded to loading with increased formation and decreased resorption, preferentially at high strains. Low strains were associated with no anabolic response in adult and elderly mice, whereas young animals showed a strong response. Adult animals showed a clear separation between strain ranges where formation and resorption occurred but without an intermediate quiescent "lazy zone". This strain threshold disappeared in elderly mice, as mechanically induced (re) modeling became dysregulated, apparent in an inability to inhibit resorption or initiate formation. Contrary to what is generally believed until now, aging does not shift the mechanical threshold required to initiate formation or resorption, but rather blurs its specificity. These data suggest that pharmaceutical strategies augmenting physical exercise should consider this dysfunction in the mechanical regulation of bone (re) modeling to more effectively combat age-related bone loss. (C) 2015 American Society for Bone and Mineral Research.