Material matters: a mechanostat-based perspective on bone development in osteogenesis imperfecta and hypophosphatemic rickets.
This perspective paper presents a hypothesis that links abnormalities of bone material with densitometric findings in two congenital metabolic bone disorders, osteogenesis imperfecta type I (OI) and X-linked hypophosphatemic rickets (XLH). Analyses of iliac bone samples from OI patients have shown that material bone density is elevated and that the bone material is abnormally stiff in this disorder. Therefore, a given mechanical load on an OI bone will generate a smaller than normal deformation. This in turn should lead osteocytes, the putative mechanosensing cells, to systematically underestimate the prevailing mechanical forces. According to the mechanostat model, bone strength should then be adapted to the underestimated mechanical loads, which means that bone architecture and mass remain below requirements. Available densitometric studies are in accordance with this hypothesis. In XLH, a mild mineralization defect persists despite treatment. This mineralization defect should lead to soft bone material. In analogy to the above model for OI, mechanical loads should be overestimated, resulting in increased densitometric parameters of bone strength. Indeed, lumbar spine areal bone mineral density is usually elevated in such patients.
Rauch
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Genetics Unit, Shriners Hospital for Children, Montreal, Canada. frauch@shriners.mcgill.ca
D001696:Biomechanical Phenomena; D015519:Bone Density / Q000502:physiology; D001846:Bone Development / Q000502:physiology*; D016723:Bone Remodeling / Q000502:physiology*; D006801:Humans; D007015:Hypophosphatemia, Familial / Q000503:physiopathology*; D008954:Models, Biological; D010011:Osteocytes / Q000502:physiology; D010013:Osteogenesis Imperfecta / Q000503:physiopathology*