A real bone mineral density (aBMD) at the distal radius can predict subsequent wrist fractures, but the actual basis for this association is uncertain. In particular, it is not clear whether fracture risk is determined by BMD per se or by some related parameter. Previously available technologies allowed some assessment of bone size (a confounder of aBMD) and geometry. However, it is now possible to explore this issue in more detail using high-resolution peripheral quantitative computerized tomography (pQCT), which can measure numerous micro- and macrostructural variables in the distal radius, along with volumetric BMD (vBMD) of cortical and trabecular bone separately. The purpose of this report [1] was to evaluate these diverse measures (BMD, bone geometry, bone microstructure, bone strength, and fall load to bone strength ratios) in a population sample of postmenopausal women with and without a prior distal forearm (Colles’) fracture (n=18 in each group).
Bone mineral density influences the risk of osteoporosis later in life and is useful in the evaluation of the risk of fracture. A recent study from Iceland [1] aimed to identify sequence variants associated with bone mineral density and fracture. A quantitative trait analysis of data was performed from 5861 Icelandic subjects (the discovery set), testing for an association between 301 019 single-nucleotide polymorphisms (SNPs) and bone mineral density of the hip and lumbar spine. The authors then tested for an association between 74 SNPs (most of which were implicated in the discovery set) at 32 loci in replication sets of Icelandic, Danish, and Australian subjects (4165, 2269, and 1491 subjects, respectively).
Bone mineral density, osteoporosis, and osteoporotic fractures: a genome-wide association study.
17/03/2009 in Clinical dataOsteoporosis is diagnosed by the measurement of bone mineral density, which is a highly heritable and multifactorial trait. A recent study [1] aimed to identify genetic loci that are associated with bone mineral density. In this genome-wide association study, the authors identified the most promising of 314 075 single nucleotide polymorphisms (SNPs) in 2094 women in a UK study. They then tested these SNPs for replication in 6463 people from three other cohorts in Western Europe. They also investigated allelic expression in lymphoblast cell lines. They tested the association between the replicated SNPs and osteoporotic fractures with data from two studies.
Human osteopetrosis due to RANKL mutations: the osteoclast is not guilty
10/03/2009 in PathophysiologyOsteopetrosis is caused by a failure of osteoclasts to resorb bone tissue, resulting in bone marrow cavities becoming occluded. Osteopetrosis is a monogenetic disease and, whenever it occurs, can be traced to a gene essential to osteoclast function. The most severe form of human osteopetrosis is the malignant, infantile, autosomal recessive variant (ARO). ARO occurs because of specific mutations in genes responsible for osteoclast function. Despite a decrease in resorption, osteoclast numbers are normal or increased. These ‘‘osteoclast-rich’’ cases suggest that the osteoclast defect does not affect osteoclast formation but rather lies in their mature functional capacity. Providing osteoclast precursors via bone marrow transplantation successfully treats these patients.
Bone alters its morphology and density in response to external loads. Lack of mechanical stimulation has been linked to bone loss in osteoporosis. Models of bone tissue predict that during loading, fluid flows through the compartments (lacunae) that house osteocytes within mineralized bone and through the channels (canaliculae) that connect lacunae to each other and to bone-forming osteoblasts at the bone surface. Experiments in cultured bone cells have shown that dynamic fluid flow stimulates osteogenic, and inhibits bone resorptive, responses. Primary cilia are solitary, immotile, microtubule-based organelles that grow from the centrosome and project from the cell surface in many vertebrate tissues, including bone. Primary cilia also function as flow sensors in kidney tubule epithelial cells where they mediate calcium entry through polycystin 2, a stretch-activated calcium channel. Mutations of polycystins cause polycystic kidney disease.
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