Bone microarchitecture, best evaluated by bone biopsy, concerns bone properties at the microscopic level, such as the spatial distribution of trabecular rods and plates, trabecular thickness and connectivity, cortical thickness and cortical porosity. The horizontal trabeculae, which stabilize the load-bearing vertical trabeculae, are subject to thinning and perforation in patients with osteoporosis, resulting in loss of bone strength and increased fracture risk [18]. The number, size, and distribution of cortical porosities may play a role in determining bone strength .
Damage accumulation, such as the increasing number of microfractures with advancing age, occurs at multiple skeletal sites in some, but perhaps not all individuals [20]. While this has adverse effects on the biomechanical properties of bone, the relationship between microfractures and clinical fractures is not clear, and the significance of increased microdamage accumulation with antiresorptive therapy is not known.
Bone matrix is the noncalcified portion of bone, 90% of which is composed of type 1 collagen. It provides elasticity and flexibility to bone. Inherited and acquired disorders of the collagen fibrils, crosslinking, or non-collagenous proteins may have serious consequences on bone strength and fracture risk. Mild forms of metabolic bone disease with abnormal collagen, such as osteogenesis imperfecta and Ehlers-Danlos syndrome, may sometimes masquerade as postmenopausal osteoporosis.
Mineralization is responsible for stiffness, or mechanical rigidity, of bone. Too much (osteopetrosis) or too little (osteomalacia) bone mineral can have adverse effects on bone strength. Mineralization takes place in two phases: the primary, or active bone formation phase, occurring over a period of months, and the secondary, or slow phase, which takes years. The second phase, which may be responsible for as much as 50% of bone mineralization, is incomplete in high bone turnover states. The rapid increase in BMD over the first 6–12 months of bisphosphonate therapy is due to "filling of the remodeling space" associated with the first phase of mineralization, while the slower increase in BMD over the following years is due to increased secondary mineralization allowed by the reduced rate of bone turnover Even the size and distribution of hydroxyapatite crystals may affect the mechanical properties of bone, with animal studies suggesting that a mix of small and large crystals are stronger than only large crystals or only small crystals
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