Mechanisms of Bone Fragility: From Osteogenesis Imperfecta to Secondary Osteoporosis

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.

Automated summary

The strength of bone material is determined by various factors, and understanding the mechanisms of rare genetic bone fragility disorders not only advances medical knowledge but also may lead to drug development for more common disorders. The main disease mechanisms underlying bone fragility associated with low bone mass include type I collagen processing, WNT signaling, TGF-β signaling, the RANKL-RANK system, and the osteocyte mechanosensing pathway.