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. · Jun 2015
Multicenter Study Clinical TrialMendelian randomization analysis to examine for a causal effect of urate on bone mineral density.
In observational studies, serum urate concentrations are positively associated with bone mineral density (BMD) and reduced risk of fragility fractures, raising the possibility that urate is a direct mediator of bone density. We used Mendelian randomization analysis to examine whether urate has a causal effect on BMD. We analyzed data from the Generation 3 cohort in the Framingham Heart Study (FHS) (N = 2501 total; 1265 male, 1236 female). ⋯ Similar findings were observed in both the male and female subgroups, and there was no evidence for causality when individual SNPs were analyzed. Serum urate is strongly associated with BMD. However, controlling for confounders by Mendelian randomization analysis does not provide evidence that increased urate has a causal effect on increasing BMD.
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J. Bone Miner. Res. · Nov 2014
Multicenter StudyRisk of Osteoporotic Fractures With Angiotensin II Receptor Blockers Versus Angiotensin-Converting Enzyme Inhibitors in Hypertensive Community-Dwelling Elderly.
Angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) are used to treat hypertension; however, in vivo and clinical studies suggest that ARBs and ACE inhibitors may exert different effects on bone. The association between long-term use of ARBs and ACE inhibitors and fracture requiring medical attention is limited. We conducted a population-based, retrospective cohort study with propensity score matching using administrative databases in Ontario, Canada, to examine the risk of osteoporosis-related fractures in hypertensive elderly treated with ARBs versus ACE inhibitors. ⋯ Among new ARB users, 27,815 (96.5%) were successfully matched to ACE inhibitor users. Without dose adjustment, no significant association was observed for ARBs relative to ACE inhibitor users for hip fractures (HR = 0.88; 95% confidence interval [CI] 0.70-1.11), with a decreased risk of other major osteoporotic fractures (HR = 0.81; CI 0.70-0.93) and no significant association for other osteoporotic fractures (HR = 0.88; CI 0.74-1.05). When adjusted for dosage, there was no significant difference between the effects of ARBs and ACE inhibitors on hip (HR = 0.99; CI 0.78-1.25), other major osteoporotic (HR = 0.87; CI 0.75-1.01), and other osteoporotic fractures (HR = 0.90; CI 0.74-1.08).
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J. Bone Miner. Res. · Feb 2014
Multicenter Study Clinical TrialMortality after lower extremity fractures in men with spinal cord injury.
In the United States, there are over 200,000 men with spinal cord injuries (SCIs) who are at risk for lower limb fractures. The risk of mortality after fractures in SCI is unknown. This was a population-based, cohort study of all male veterans (mean age 54.1; range, 20.3-100.5 years) with a traumatic SCI of at least 2 years' duration enrolled in the Veterans Affairs (VA) Spinal Cord Dysfunction Registry from FY2002 to FY2010 to determine the association between lower extremity fractures and mortality. ⋯ In fully-adjusted models, the association of incident lower extremity fracture with increased mortality was substantially greater in older men (age ≥50 years) for the entire cohort (HR, 3.42; 95% CI, 2.75-4.25) and for those with complete SCI (HR, 3.13; 95% CI, 2.19-4.45), compared to younger men (age <50 years) (entire cohort: HR, 1.42; 95% CI, 0.94-2.14; complete SCI: HR, 1.71; 95% CI, 0.98-3.01). Every additional point in the Charlson comorbidity index was associated with a 10% increase in the hazard of death in models involving the entire cohort (HR, 1.11; 95% CI, 1.09-1.13) and also in models limited to men with complete SCI (HR, 1.10; 95% CI, 1.06-1.15). These data support the concept that both the fracture itself and underlying comorbidities are drivers of death in men with SCI.
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J. Bone Miner. Res. · Jan 2014
Multicenter Study Clinical TrialSkeletal structure in postmenopausal women with osteopenia and fractures is characterized by abnormal trabecular plates and cortical thinning.
The majority of fragility fractures occur in women with osteopenia rather than osteoporosis as determined by dual‐energy X‐ray absorptiometry (DXA). However, it is difficult to identify which women with osteopenia are at greatest risk. We performed this study to determine whether osteopenic women with and without fractures had differences in trabecular morphology and biomechanical properties of bone. ⋯ Differences in cortical bone were found at both sites, whereas trabecular differences were more pronounced at the radius. In summary, postmenopausal women with osteopenia and fractures had lower cortical and trabecular vBMD; thinner, more widely separated and rodlike trabecular structure; less trabecular connectivity; and lower whole bone stiffness compared with controls,despite similar aBMD by DXA. Our results suggest that in addition to trabecular and cortical bone loss, changes in plate and rod structure may be important mechanisms of fracture in postmenopausal women with osteopenia.
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J. Bone Miner. Res. · Aug 2013
Randomized Controlled Trial Multicenter StudyEffects of iron deficiency anemia and its treatment on fibroblast growth factor 23 and phosphate homeostasis in women.
Fibroblast growth factor 23 (FGF23) is an osteocyte-derived hormone that regulates phosphate and vitamin D homeostasis. Through unknown mechanisms, certain intravenous iron preparations induce acute, reversible increases in circulating FGF23 levels that lower serum phosphate in association with inappropriately low levels of calcitriol, similar to genetic diseases of primary FGF23 excess. In contrast, studies in wild-type mice suggest that iron deficiency stimulates fgf23 transcription but does not result in hypophosphatemia because FGF23 is cleaved within osteocytes by an unknown catabolic system. ⋯ Reduced serum phosphate was accompanied by increased urinary fractional excretion of phosphate, decreased calcitriol levels, and increased parathyroid hormone levels. These findings suggest that iron deficiency increases cFGF23 levels, and that certain iron preparations temporarily increase iFGF23 levels. We propose that intravenous iron lowers cFGF23 in humans by reducing fgf23 transcription as it does in mice, whereas carbohydrate moieties in certain iron preparations may simultaneously inhibit FGF23 degradation in osteocytes leading to transient increases in iFGF23 and reduced serum phosphate.