Department of Paediatrics and Adolescent Medicine, Johannes Kepler University Linz, Krankenhausstraße 26-30, 4020 Linz, Austria.
Int J Mol Sci. 2021 Jan 10;22(2):625. doi: 10.3390/ijms22020625.
Bone material strength is determined by several factors, such as bone mass, matrix composition, mineralization, architecture and shape. From a clinical perspective, bone fragility is classified as primary (i.e., genetic and rare) or secondary (i.e., acquired and common) osteoporosis. Understanding the mechanism of rare genetic bone fragility disorders not only advances medical knowledge on rare diseases, it may open doors for drug development for more common disorders (i.e., postmenopausal osteoporosis). In this review, we highlight the main disease mechanisms underlying the development of human bone fragility associated with low bone mass known to date. The pathways we focus on are type I collagen processing, WNT-signaling, TGF-ß signaling, the RANKL-RANK system and the osteocyte mechanosensing pathway. We demonstrate how the discovery of most of these pathways has led to targeted, pathway-specific treatments.
骨材料强度由多种因素决定，如骨量、基质组成、矿化、结构和形状。从临床角度来看，骨脆性分为原发性（即遗传和罕见）或继发性（即获得性和常见）骨质疏松症。了解罕见遗传性骨脆性疾病的机制不仅可以增进对罕见疾病的医学认识，还可能为更常见疾病（即绝经后骨质疏松症）的药物开发开辟道路。在这篇综述中，我们强调了迄今为止已知与低骨量相关的人类骨脆性发展的主要疾病机制。我们关注的途径是 I 型胶原蛋白加工、WNT 信号、TGF-β 信号、RANKL-RANK 系统和骨细胞机械敏感途径。我们展示了大多数这些途径的发现如何导致靶向、途径特异性的治疗。
