Garnero Patrick
INSERM UMR 1033, Lyon, France,
Calcif Tissue Int. 2015 Sep;97(3):229-40. doi: 10.1007/s00223-015-9996-2. Epub 2015 Apr 17.
Bone is a complex tissue constituted by a collagen matrix filled in with crystal of hydroxyapatite (HAP). Bone mechanical properties are influenced by the collagen matrix which is organized into hierarchical structures from the individual type I collagen heterotrimer flanked by linear telopeptides at each end to the collagen fibrils that are interconnected by enzymatic and non-enzymatic cross-links. Although most studies focused on the role of collagen cross-links in bone strength, other organizational features may also play a role. At the molecular level it has been shown that homotrimer of type I collagen found in bone tissue of some patients with osteogenesis imperfecta (OI) is characterized by decreased mechanical competence compared to the regular heterotrimer. The state of C-telopeptide isomerization-which can be estimated by the measurement in body fluids of the native and isomerized isoforms-has also been shown to be associated with bone strength, particularly the post-yield properties independent of bone size and bone mineral density. Other higher hierarchical features of collagen organization have shown to be associated with changes in bone mechanical behavior in ex vivo models and may also be relevant to explain bone fragility in diseases characterized by collagen abnormalities e.g., OI and Paget's disease. These include the orientation of collagen fibrils in a regular longitudinal direction, the D-spacing period between collagen fibrils and the collagen-HAP interfacial bonding. Preliminary data indicate that some of these organizational features can change during treatment with bisphosphonate, raloxifene, and PTH suggesting that they may contribute to their anti-fracture efficacy. It remains however to be determined which of these parameters play a specific and independent role in bone matrix properties, what is the magnitude of mechanical strength explained by collagen organization, whether they are relevant to explain osteoporosis-induced bone fragility, and how they could be monitored non-invasively to develop efficient bone quality biomarkers.
骨是一种复杂的组织，由填充有羟基磷灰石（HAP）晶体的胶原基质构成。骨的力学性能受胶原基质影响，胶原基质从两端带有线性端肽的单个I型胶原异源三聚体组织成层次结构，再到通过酶促和非酶促交联相互连接的胶原纤维。尽管大多数研究集中在胶原交联在骨强度中的作用，但其他组织特征可能也起作用。在分子水平上，已表明在一些成骨不全（OI）患者的骨组织中发现的I型胶原同三聚体与正常异源三聚体相比，机械性能降低。C-端肽异构化状态（可通过测量体液中天然和异构化异构体来估计）也已表明与骨强度相关，特别是与骨大小和骨矿物质密度无关的屈服后性能。胶原组织的其他更高层次特征已表明与体外模型中骨力学行为的变化有关，也可能与解释以胶原异常为特征的疾病（如OI和佩吉特病）中的骨脆性有关。这些特征包括胶原纤维在规则纵向方向上的取向、胶原纤维之间的D间距周期以及胶原-HAP界面结合。初步数据表明，这些组织特征中的一些在使用双膦酸盐、雷洛昔芬和甲状旁腺激素治疗期间会发生变化，这表明它们可能有助于其抗骨折疗效。然而，仍有待确定这些参数中哪些在骨基质特性中起特定和独立的作用，胶原组织所解释的机械强度大小是多少，它们是否与解释骨质疏松症引起的骨脆性相关，以及如何通过非侵入性监测来开发有效的骨质量生物标志物。
