Department of Orthopaedics, Mount Sinai School of Medicine, New York, NY, USA.
J Bone Miner Res. 2011 Dec;26(12):2872-85. doi: 10.1002/jbmr.497.
Having a better understanding of how complex systems like bone compensate for the natural variation in bone width to establish mechanical function will benefit efforts to identify traits contributing to fracture risk. Using a collection of pQCT images of the tibial diaphysis from 696 young adult women and men, we tested the hypothesis that bone cells cannot surmount the nonlinear relationship between bone width and whole bone stiffness to establish functional equivalence across a healthy population. Intrinsic cellular constraints limited the degree of compensation, leading to functional inequivalence relative to robustness, with slender tibias being as much as two to three times less stiff relative to body size compared with robust tibias. Using Path Analysis, we identified a network of compensatory trait interactions that explained 79% of the variation in whole-bone bending stiffness. Although slender tibias had significantly less cortical area relative to body size compared with robust tibias, it was the limited range in tissue modulus that was largely responsible for the functional inequivalence. Bone cells coordinately modulated mineralization as well as the cortical porosity associated with internal bone multicellular units (BMU)-based remodeling to adjust tissue modulus to compensate for robustness. Although anecdotal evidence suggests that functional inequivalence is tolerated under normal loading conditions, our concern is that the functional deficit of slender tibias may contribute to fracture susceptibility under extreme loading conditions, such as intense exercise during military training or falls in the elderly. Thus, we show the natural variation in bone robustness was associated with predictable functional deficits that were attributable to cellular constraints limiting the amount of compensation permissible in human long bone. Whether these cellular constraints can be circumvented prophylactically to better equilibrate function among individuals remains to be determined.
更好地理解骨骼等复杂系统如何补偿骨骼宽度的自然变化以建立机械功能，将有助于识别导致骨折风险的特征。我们使用了 696 名年轻成年男女的胫骨骨干 pQCT 图像集，检验了这样一个假设，即骨细胞无法克服骨宽度与整体骨刚度之间的非线性关系，以在健康人群中建立功能等效性。内在细胞限制限制了补偿的程度，导致与稳健性相比存在功能不等效，与粗壮的胫骨相比，细长的胫骨的刚度相对身体大小要小 2 到 3 倍。通过路径分析，我们确定了一个补偿性状相互作用的网络，该网络解释了整体骨弯曲刚度变化的 79%。尽管与粗壮的胫骨相比，细长的胫骨的皮质面积相对身体大小明显较小，但主要是组织模量的有限范围导致了功能不等效。骨细胞协调地调节矿化以及与基于内部骨多细胞单元 (BMU) 的重塑相关的皮质孔隙率，以调整组织模量来补偿稳健性。虽然轶事证据表明，在正常加载条件下，功能不等效是可以容忍的，但我们担心细长胫骨的功能缺陷可能会导致在极端加载条件下（例如军事训练期间的剧烈运动或老年人跌倒）骨折易感性。因此，我们表明，骨骼稳健性的自然变化与可预测的功能缺陷相关，这些缺陷归因于细胞限制，限制了人类长骨中允许的补偿量。这些细胞限制是否可以预防性地规避以更好地平衡个体之间的功能，还有待确定。
