Mechanisms of Bone Fragility: From Osteogenesis Imperfecta to Secondary Osteoporosis

• Published in: International journal of molecular sciences Vol. 22; no. 2; p. 625
• Main Authors: El-Gazzar, Ahmed, Högler, Wolfgang
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 10.01.2021; MDPI
• Subjects: Biomedical materials; Bone composition; bone fragility; Bone mass; Bone matrix; Bones; Classification; Collagen; Collagen (type I); Collagen Type I - metabolism; Drug development; Endoplasmic reticulum; Extracellular matrix; Fractures; Fragility; Genes; Humans; Information processing; Juvenile Paget disease; Mineralization; Mutation; Osteogenesis; Osteogenesis imperfecta; Osteogenesis Imperfecta - etiology; Osteogenesis Imperfecta - genetics; Osteogenesis Imperfecta - metabolism; Osteoporosis; Osteoporosis - etiology; Osteoporosis - genetics; Osteoporosis - metabolism; Post-menopause; post-translational modifications; Proteins; RANK Ligand - metabolism; Rare diseases; Receptor Activator of Nuclear Factor-kappa B - metabolism; Review; Signal transduction; TRANCE protein; Transforming Growth Factor beta - metabolism; type I collagen; Wnt protein; Wnt Signaling Pathway; osteomalacia; osteopetrosis; bone fragility; Juvenile Paget disease; type I collagen; post-translational modifications; osteogenesis imperfecta; extracellular matrix
• ISSN: 1422-0067; 1661-6596; 1422-0067
• 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.