Abstract
Bone fragility is a pathological condition caused by altered homeostasis of the mineralized bone mass with deterioration of the microarchitecture of the bone tissue, which results in a reduction of bone strength and an increased risk of fracture, even in the absence of high-impact trauma. The most common cause of bone fragility is primary osteoporosis in the elderly. However, bone fragility can manifest at any age, within the context of a wide spectrum of congenital rare bone metabolic diseases in which the inherited genetic defect alters correct bone modeling and remodeling at different points and aspects of bone synthesis and/or bone resorption, leading to defective bone tissue highly prone to long bone bowing, stress fractures and pseudofractures, and/or fragility fractures. To date, over 100 different Mendelian-inherited metabolic bone disorders have been identified and included in the OMIM database, associated with germinal heterozygote, compound heterozygote, or homozygote mutations, affecting over 80 different genes involved in the regulation of bone and mineral metabolism. This manuscript reviews clinical bone phenotypes, and the associated bone fragility in rare congenital metabolic bone disorders, following a disease taxonomic classification based on deranged bone metabolic activity.
Highlights
Bone is a mineralized connective tissue, which exerts important biological functions, such as locomotion, support, and protection of soft tissues and organs, as well as being the storage of calcium and phosphate [1].Despite its inert appearance, bone is a highly active tissue, continuously undergoing a remodeling process, by which the old tissue is replaced by new bone, granting the skeleton the ability to adapt to mechanical use, correct calcium and phosphate homeostasis, and to heal fractures
Bone is a highly active tissue, continuously undergoing a remodeling process, by which the old tissue is replaced by new bone, granting the skeleton the ability to adapt to mechanical use, correct calcium and phosphate homeostasis, and to heal fractures
An imbalance between these two phases results in bone fragility, a pathological condition in which the correct bone microarchitecture is altered, the strength of bone tissue is reduced, and the skeleton is prone to deformities and fractures, even in the presence of low-impact traumas or with no trauma [2]
Summary
Bone is a mineralized connective tissue (hard tissue), which exerts important biological functions, such as locomotion, support, and protection of soft tissues and organs, as well as being the storage of calcium and phosphate [1]. Bone fragility can be caused by excessive osteoclast-driven bone resorption that is not balanced by a corresponding amount of bone formation, which leads to bone mass loss and “porous bone” (osteoporosis), or by disfunctions affecting the correct mineralization process of the extracellular matrix leading to “soft bone” (a pathological condition named osteomalacia in adults and rickets in children), or by an excessive bone mass (osteopetrosis) being the outcome of an enhanced osteoblast-driven mineralized bone deposition or a reduced resorption activity by the osteoclasts Despite their different molecular causes and histological manifestations, these bone pathological conditions confer an elevated rate of deformities to the tissue and notably increase the risk of fragility fractures. Bone fragility can manifest at any age, as a consequence of a wide spectrum of rare congenital metabolic bone disorders, in which the inherited genetic defect compromises the correct bone tissue modeling and remodeling, causing bone deformities and fragility fractures
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