Older persons with hip fractures remain at increased risk of subsequent hip fractures. However, little is known about the frequency and characteristics of persons who sustain a second hip fracture. A recent study addressed this question [1]. Participants included 481 members of the Framingham Heart Study who sustained an initial hip fracture between April 1952 and December 31, 2003. Participants were followed up until a second hip fracture, death, dropout, or study completion. Age, sex, falls, stroke, dementia, residence, recent weight change, body mass index, and functional status were considered potential predictors of a second hip fracture.
Vitamin D plays an essential role in skeletal metabolism by binding to its nuclear steroid receptor, the vitamin D receptor (VDR). The heritability of bone mineral density (BMD) is well established, and the VDR gene is considered a prime candidate suggested to partially account for genetically controlled BMD variance in the population. The aim of a recent study was to reconstruct common haplotypes in the VDR 3’ untranslated region (UTR) and studied the association to BMD and risk of vertebral fractures in 3014 elderly men from Sweden and 2000 in Hong Kong, all participants of the global MrOS Study. To assess any functional implications of the VDR polymorphisms, the authors studied allele-specific expressions of the different VDR 3’ UTR haplotypes in the normal chromosomal context of 70 unrelated human trabecular bone samples. This was performed by quantitative genotyping of coding polymorphisms in RNA samples and in corresponding DNA samples isolated from the bone samples.
Osteoclasts (OCs) are large multinucleated cells of hematopoietic origin formed by the differentiation and fusion of mononuclear monocyte–macrophage lineage precursors after stimulation by RANKL and macrophage colony-stimulating factor (M-CSF). OC access to the bone surface requires precursor recruitment from the circulation into bone and a capacity to migrate to find their way to suitable stromal sites for their development into bone-resorptive mature multinucleated OCs (MMOCs). Mononucleated osteoclasts precursors (pre-OCs) have the capacity to transmigrate through endothelial cells. MMOCs also exhibit several features usually involved in cell invasion such as expression of the proto-oncogene c-src. Disruption of c-src leads to osteopetrosis in mice, resulting in the excessive accumulation of bone matrix caused by defective OC functions. Matrix metalloproteinases (MMPs), which play a major role in tumor cell invasion and metastasis, are also involved in OC function by promoting their recruitment and the degradation of the mineralized bone matrix. Finally, OCs exhibit podosomes, highly dynamic actin-rich structures involved in adhesion, migration, and matrix degradation, and sealing zones insuring attachment to bone surface.
Strontium ranelate is an agonist of the calcium-sensing receptor, which mediates its effects on osteoblasts
07/10/2008 in Clinical dataStrontium ranelate is proposed as a preventive and curative treatment of osteoporosis that reduces the risk of both vertebral, nonvertebral, and hip fractures in postmenopausal women. Strontium ranelate has been shown to reduce bone resorption by osteoclasts, and to stimulate bone formation by osteoblasts (OBs), rebalancing bone turnover in favor of bone formation.
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