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. · Apr 2015
Sclerostin inhibition prevents spinal cord injury-induced cancellous bone loss.
Spinal cord injury (SCI) results in rapid and extensive sublesional bone loss. Sclerostin, an osteocyte-derived glycoprotein that negatively regulates intraskeletal Wnt signaling, is elevated after SCI and may represent a mechanism underlying this excessive bone loss. However, it remains unknown whether pharmacologic sclerostin inhibition ameliorates bone loss subsequent to SCI. ⋯ Specifically, Scl-Ab increased osteoblast surface and bone formation, indicating direct bone anabolic effects, whereas TE reduced osteoclast surface with minimal effect on bone formation, indicating antiresorptive effects. The deleterious microarchitectural alterations in the trabecular network were also prevented in SCI + Scl-Ab and SCI + TE animals, whereas only Scl-Ab completely prevented the reduction in cortical bone strength. Our findings provide the first evidence indicating that sclerostin inhibition represents a viable treatment to prevent SCI-induced cancellous and cortical bone deficits and provides preliminary rationale for future clinical trials focused on evaluating whether Scl-Ab prevents osteoporosis in the SCI population.
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J. Bone Miner. Res. · Apr 2015
Biography Historical ArticleIn memoriam: Stephen Hough 27/08/1947-05/12/2014.
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J. Bone Miner. Res. · Jan 2015
Randomized Controlled Trial Comparative StudyComparative effects of teriparatide, denosumab, and combination therapy on peripheral compartmental bone density, microarchitecture, and estimated strength: the DATA-HRpQCT Study.
Combined teriparatide and denosumab increases spine and hip bone mineral density more than either drug alone. The effect of this combination on skeletal microstructure and microarchitecture, however, is unknown. Because skeletal microstructure and microarchitecture are important components of skeletal integrity, we performed high-resolution peripheral quantitative computed tomography (HR-pQCT) assessments at the distal tibia and radius in postmenopausal osteoporotic women randomized to receive teriparatide 20 µg daily (n = 31), denosumab 60 mg every 6 months (n = 33), or both (n = 30) for 12 months. ⋯ In the teriparatide group, radial cortical porosity increased by 20.9 ± 37.6% and by 5.6 ± 9.9% at the tibia but did not change in the other two groups. Bone stiffness and failure load, as estimated by finite element analysis, did not change in the teriparatide group but increased in the other two groups at both sites. Together, these findings suggest that the use of denosumab and teriparatide in combination improves HR-pQCT measures of bone quality more than either drug alone and may be of significant clinical benefit in the treatment of postmenopausal osteoporosis.
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J. Bone Miner. Res. · Dec 2014
Reviewunveiling skeletal fragility in patients diagnosed with MGUS: no longer a condition of undetermined significance?
Monoclonal gammopathy of undetermined significance (MGUS) is a common finding in clinical practice, affecting greater than 3% of adults aged 50 years and older. As originally described, the term MGUS reflected the inherent clinical uncertainty of distinguishing patients with a benign stable monoclonal plasma cell disorder from subjects destined to progress to malignancy. There is now clear epidemiologic evidence, however, that patients with MGUS suffer from a significantly increased fracture risk and that the prevalence of MGUS is increased in patients with osteoporosis. ⋯ Recent work has demonstrated that circulating levels of at least two cytokines (CCL3/MIP-1α and DKK1) with well-recognized roles in bone disease in the related monoclonal gammopathy multiple myeloma are also increased in patients with MGUS. Further, recent imaging studies using high-resolution peripheral quantitative CT have documented that patients with MGUS have substantial skeletal microarchitectural deterioration and deficits in biomechanical bone strength that likely underlie the increased skeletal fragility in these patients. Accordingly, this Perspective provides evidence that the "undetermined significance" portion of the MGUS acronym may be best replaced in favor of the term "monoclonal gammopathy of skeletal significance" (MGSS) in order to more accurately reflect the enhanced skeletal risks inherent in this condition.