Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research
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J. Bone Miner. Res. · Aug 2011
Central (ICV) leptin injection increases bone formation, bone mineral density, muscle mass, serum IGF-1, and the expression of osteogenic genes in leptin-deficient ob/ob mice.
Both central and peripheral leptin administrations reduce body weight, food intake, and adiposity in ob/ob mice. In this study we compared effects of intracerebroventricular (ICV) and subcutaneous (SC) administration of leptin on bone metabolism in the appendicular and axial skeleton and adipose tissue gene expression and determined the effects of ICV leptin on bone marrow gene expression in ob/ob mice. In experiment 1, leptin (1.5 or 0.38 µg/d) or control was continuously injected ICV for 12 days. ⋯ Serum insulin was decreased, whereas serum osteocalcin, insulin-like growth factor 1, osteoprotegerin, pyridinoline, and receptor activator of nuclear factor κB ligand concentrations were increased. In experiment 2, expression of genes in adipose tissue associated with apoptosis, lipid mobilization, insulin sensitivity, and thermogenesis was increased, whereas expression of genes associated with cell differentiation and maturation was decreased regardless of mode of administration. Thus ICV injection of leptin promotes expression of pro-osteogenic factors in bone marrow, leading to enhanced bone formation in ob/ob mice.
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J. Bone Miner. Res. · Aug 2011
Mild hyponatremia as a risk factor for fractures: the Rotterdam Study.
Recent studies suggest that mild hyponatremia is associated with fractures, but prospective studies are lacking. We studied whether hyponatremia is associated with fractures, falls, and/or bone mineral density (BMD). A total of 5208 elderly subjects with serum sodium assessed at baseline were included from the prospective population-based Rotterdam Study. ⋯ Finally, all-cause mortality was higher in subjects with hyponatremia (HR = 1.21, 95% CI 1.03-1.43, p = .022). It is concluded that mild hyponatremia in the elderly is associated with an increased risk of vertebral fractures and incident nonvertebral fractures but not with BMD. Increased fracture risk in hyponatremia also was independent of recent falls, pointing toward a possible effect on bone quality.
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Leptin, a major hormonal product of the adipocyte, regulates appetite and reproductive function through its hypothalamic receptors. The leptin receptor is present in osteoblasts and chondrocytes, and previously we have shown leptin to be an anabolic bone factor in vitro, stimulating osteoblast proliferation and inhibiting osteoclastogenesis. Leptin increases bone mass and reduces bone fragility when administered peripherally but also can indirectly reduce bone mass when administered into the central nervous system. ⋯ The material properties of db/db femurs were determined by three-point bending and nanoindentation, showing decreased bone strength (13.3 ± 0.280 N versus 7.99 ± 0.984 N, p = .0074) and material stiffness (28.5 ± 0.280 GPa versus 25.8 ± 0.281 GPa, p < .0001). These results demonstrate that bone mass and strength are reduced in the absence of leptin signaling, indicating that leptin acts in vivo as an anabolic bone factor. This concurs with results of in vitro studies and of peripheral leptin administration in vivo and suggests that leptin's direct effects on bone cells are likely to override its actions via the central nervous system.
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J. Bone Miner. Res. · Jul 2011
Mortality risk for operated and nonoperated vertebral fracture patients in the medicare population.
Vertebral compression fractures (VCFs) are associated with increased mortality risk, but the association between surgical treatment and survivorship is unclear. We evaluated the mortality risk for VCF patients undergoing conservative treatment (nonoperated), kyphoplasty, and vertebroplasty. Survival of VCF patients in the 100% U. ⋯ The relative risk of mortality for kyphoplasty patients was 23% lower than that for vertebroplasty patients (adjusted HR = 0.77, p < .001). Using physician preference as an instrument, the absolute difference in the adjusted survival rate at 3 years was 7.29% higher in patients receiving kyphoplasty than vertebroplasty (p < .001), compared with a crude absolute rate difference of 5.09%. This study established the mortality risk associated with VCFs diagnosed between 2005 and 2008 with respect to different treatment modalities for elderly patients in the entire Medicare population.
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J. Bone Miner. Res. · Jul 2011
Randomized Controlled TrialBalloon kyphoplasty for the treatment of acute vertebral compression fractures: 2-year results from a randomized trial.
Vertebral fractures are often painful and lead to reduced quality of life and disability. We compared the efficacy and safety of balloon kyphoplasty to nonsurgical therapy over 24 months in patients with acute painful fractures. Adults with one to three vertebral fractures were randomized within 3 months from onset of pain to undergo kyphoplasty (n = 149) or nonsurgical therapy (n = 151). ⋯ Compared with nonsurgical management, kyphoplasty rapidly reduces pain and improves function, disability, and quality of life without increasing the risk of additional vertebral fractures. The differences from nonsurgical management are statistically significant when averaged across 24 months. Most outcomes are not statistically different at 24 months, but the reduction in back pain remains statistically significant at all time points.