| 61. |
- Harvey, Nicholas C., et al.
(författare)
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Sarcopenia Definitions as Predictors of Fracture Risk Independent of FRAX®, Falls, and BMD in the Osteoporotic Fractures in Men (MrOS) Study : A Meta-Analysis
- 2021
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Ingår i: Journal of Bone and Mineral Research. - : Wiley. - 0884-0431 .- 1523-4681. ; 36:7, s. 1235-1244
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Tidskriftsartikel (refereegranskat)abstract
- Dual-energy X-ray absorptiometry (DXA)-derived appendicular lean mass/height2 (ALM/ht2) is the most commonly used estimate of muscle mass in the assessment of sarcopenia, but its predictive value for fracture is substantially attenuated by femoral neck (fn) bone mineral density (BMD). We investigated predictive value of 11 sarcopenia definitions for incident fracture, independent of fnBMD, fracture risk assessment tool (FRAX®) probability, and prior falls, using an extension of Poisson regression in US, Sweden, and Hong Kong Osteoporois Fractures in Men Study (MrOS) cohorts. Definitions tested were those of Baumgartner and Delmonico (ALM/ht2 only), Morley, the International Working Group on Sarcopenia, European Working Group on Sarcopenia in Older People (EWGSOP1 and 2), Asian Working Group on Sarcopenia, Foundation for the National Institutes of Health (FNIH) 1 and 2 (using ALM/body mass index [BMI], incorporating muscle strength and/or physical performance measures plus ALM/ht2), and Sarcopenia Definitions and Outcomes Consortium (gait speed and grip strength). Associations were adjusted for age and time since baseline and reported as hazard ratio (HR) for first incident fracture, here major osteoporotic fracture (MOF; clinical vertebral, hip, distal forearm, proximal humerus). Further analyses adjusted additionally for FRAX-MOF probability (n = 7531; calculated ± fnBMD), prior falls (y/n), or fnBMD T-score. Results were synthesized by meta-analysis. In 5660 men in USA, 2764 Sweden and 1987 Hong Kong (mean ages 73.5, 75.4, and 72.4 years, respectively), sarcopenia prevalence ranged from 0.5% to 35%. Sarcopenia status, by all definitions except those of FNIH, was associated with incident MOF (HR = 1.39 to 2.07). Associations were robust to adjustment for prior falls or FRAX probability (without fnBMD); adjustment for fnBMD T-score attenuated associations. EWGSOP2 severe sarcopenia (incorporating chair stand time, gait speed, and grip strength plus ALM) was most predictive, albeit at low prevalence, and appeared only modestly influenced by inclusion of fnBMD. In conclusion, the predictive value for fracture of sarcopenia definitions based on ALM is reduced by adjustment for fnBMD but strengthened by additional inclusion of physical performance measures.
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| 62. |
- Harvey, N. C., et al.
(författare)
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Sarcopenia Definitions as Predictors of Fracture Risk Independent of FRAX(R), Falls, and BMD in the Osteoporotic Fractures in Men (MrOS) Study: A Meta-Analysis
- 2021
-
Ingår i: Journal of Bone and Mineral Research. - : Wiley. - 0884-0431 .- 1523-4681. ; 36:7, s. 1235-1244
-
Tidskriftsartikel (refereegranskat)abstract
- Dual-energy X-ray absorptiometry (DXA)-derived appendicular lean mass/height(2) (ALM/ht(2)) is the most commonly used estimate of muscle mass in the assessment of sarcopenia, but its predictive value for fracture is substantially attenuated by femoral neck (fn) bone mineral density (BMD). We investigated predictive value of 11 sarcopenia definitions for incident fracture, independent of fnBMD, fracture risk assessment tool (FRAX(R)) probability, and prior falls, using an extension of Poisson regression in US, Sweden, and Hong Kong Osteoporois Fractures in Men Study (MrOS) cohorts. Definitions tested were those of Baumgartner and Delmonico (ALM/ht(2) only), Morley, the International Working Group on Sarcopenia, European Working Group on Sarcopenia in Older People (EWGSOP1 and 2), Asian Working Group on Sarcopenia, Foundation for the National Institutes of Health (FNIH) 1 and 2 (using ALM/body mass index [BMI], incorporating muscle strength and/or physical performance measures plus ALM/ht(2)), and Sarcopenia Definitions and Outcomes Consortium (gait speed and grip strength). Associations were adjusted for age and time since baseline and reported as hazard ratio (HR) for first incident fracture, here major osteoporotic fracture (MOF; clinical vertebral, hip, distal forearm, proximal humerus). Further analyses adjusted additionally for FRAX-MOF probability (n = 7531; calculated +/- fnBMD), prior falls (y/n), or fnBMD T-score. Results were synthesized by meta-analysis. In 5660 men in USA, 2764 Sweden and 1987 Hong Kong (mean ages 73.5, 75.4, and 72.4 years, respectively), sarcopenia prevalence ranged from 0.5% to 35%. Sarcopenia status, by all definitions except those of FNIH, was associated with incident MOF (HR = 1.39 to 2.07). Associations were robust to adjustment for prior falls or FRAX probability (without fnBMD); adjustment for fnBMD T-score attenuated associations. EWGSOP2 severe sarcopenia (incorporating chair stand time, gait speed, and grip strength plus ALM) was most predictive, albeit at low prevalence, and appeared only modestly influenced by inclusion of fnBMD. In conclusion, the predictive value for fracture of sarcopenia definitions based on ALM is reduced by adjustment for fnBMD but strengthened by additional inclusion of physical performance measures. (c) 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR)..
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| 63. |
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| 64. |
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| 65. |
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| 66. |
- Hesse, Bernhard, et al.
(författare)
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Canalicular Network Morphology is the Major Determinant of the Spatial Distribution of Mass Density in Human Bone Tissue : Evidence by Means of Synchrotron Radiation Phase-Contrast nano-CT
- 2015
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Ingår i: Journal of Bone and Mineral Research. - : Wiley. - 0884-0431 .- 1523-4681. ; 30:2, s. 346-356
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Tidskriftsartikel (refereegranskat)abstract
- In bone remodeling, maturation of the newly formed osteonal tissue is associated with a rapid primary increase followed by a slower secondary increase of mineralization. This requires supply and precipitation of mineral into the bone matrix. Mineral delivery can occur only from the extracellular fluid via interfaces such as the Haversian system and the osteocyte pore network. We hypothesized that in mineralization, mineral exchange is achieved by the diffusion of mineral from the lacunar-canalicular network (LCN) to the bone matrix, resulting in a gradual change in tissue mineralization with respect to the distance from the pore-matrix interface. We expected to observe alterations in the mass density distribution with tissue age. We further hypothesized that mineral exchange occurs not only at the lacunar but also at the canalicular boundaries. The aim of this study was, therefore, to investigate the spatial distribution of mass density in the perilacunar and pericanalicular bone matrix and to explore how these densities are influenced by tissue aging. This is achieved by analyzing human jawbone specimens originating from four healthy donors and four treated with high-dosage bisphosphonate using synchrotron radiation phase-contrast nano-CT with a 50-nm voxel size. Our results provide the first experimental evidence that mass density in the direct vicinity of both lacunae (p<0.001) and canaliculi (p<0.001) is different from the mean matrix mass density, resulting in gradients with respect to the distance from both pore-matrix interfaces, which diminish with increasing tissue age. Though limited by the sample size, these findings support our hypotheses. Moreover, the density gradients are more pronounced around the lacunae than around the canaliculi, which are explained by geometrical considerations in the LCN morphology. In addition, we speculate that mineral exchange occurs at all interfaces of the LCN, not only in mineralization but also in mineral homeostasis.
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| 67. |
- Holmer, Helene, et al.
(författare)
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Fracture incidence in GH-deficient patients on complete hormone replacement including GH
- 2007
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Ingår i: Journal of Bone and Mineral Research. - : Wiley. - 0884-0431 .- 1523-4681. ; 22:12, s. 1842-1850
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Tidskriftsartikel (refereegranskat)abstract
- Fracture risk in GHD patients is not definitely established. Studying fracture incidence in 832 patients on GH therapy and 2581 matched population controls, we recorded a doubled fracture risk in CO GHD women, but a significantly lower fracture risk in AO GHD men. Introduction: The objective of this study was to evaluate fracture incidence in patients wilh confirmed growth hormone deficiency (GHD) on replacement therapy (including growth hormone [GH]) compared with population controls, while also taking potential confounders and effect modifiers into account. Materials and Methods: Eight hundred thirty-two patients with GHD and 2581 matched population controls answered a questionnaire about fractures and other background information. Incidence rate ratio (IRR) and 95% CI for first fracture were estimated. The median time on GH therapy for childhood onset (CO) GHD men and women was 15 and 12 yr, respectively, and 6 and 5 yr for adult onset (AO) GHD men and women, respectively. Results: A more than doubled risk (IRR, 2.29; 95% CI, 1.23-4.28) for nonosteoporotic fractures was recorded in women with CO GHD, whereas no risk increase was observed among CO GHD men (IRR. 0.61) and AO GHD women (IRR, 1.08). A significantly decreased incidence of fractures (IRR, 0.54; 95% CI 0.34-0.86) was recorded in AO GHD men. Conclusions: Increased fracture risk in CO GHD women can most likely be explained by interaction between oral estrogen and the GH-IGF-I axis. The adequate substitution rate of testosterone (90%) and GH (94%) may have resulted in significantly lower fracture risk in AO GHD men.
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| 68. |
- Hsu, Y. H., et al.
(författare)
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Meta-Analysis of Genomewide Association Studies Reveals Genetic Variants for Hip Bone Geometry
- 2019
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Ingår i: Journal of Bone and Mineral Research. - : Wiley. - 0884-0431 .- 1523-4681. ; 34:7, s. 1284-1296
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Tidskriftsartikel (refereegranskat)abstract
- Hip geometry is an important predictor of fracture. We performed a meta-analysis of GWAS studies in adults to identify genetic variants that are associated with proximal femur geometry phenotypes. We analyzed four phenotypes: (i) femoral neck length; (ii) neck-shaft angle; (iii) femoral neck width, and (iv) femoral neck section modulus, estimated from DXA scans using algorithms of hip structure analysis. In the Discovery stage, 10 cohort studies were included in the fixed-effect meta-analysis, with up to 18,719 men and women ages 16 to 93 years. Association analyses were performed with similar to 2.5 million polymorphisms under an additive model adjusted for age, body mass index, and height. Replication analyses of meta-GWAS significant loci (at adjusted genomewide significance [GWS], threshold p <= 2.6 x 10(-8)) were performed in seven additional cohorts in silico. We looked up SNPs associated in our analysis, for association with height, bone mineral density (BMD), and fracture. In meta-analysis (combined Discovery and Replication stages), GWS associations were found at 5p15 (IRX1 and ADAMTS16); 5q35 near FGFR4; at 12p11 (in CCDC91); 11q13 (near LRP5 and PPP6R3 (rs7102273)). Several hip geometry signals overlapped with BMD, including LRP5 (chr. 11). Chr. 11 SNP rs7102273 was associated with any-type fracture (p = 7.5 x 10(-5)). We used bone transcriptome data and discovered several significant eQTLs, including rs7102273 and PPP6R3 expression (p = 0.0007), and rs6556301 (intergenic, chr.5 near FGFR4) and PDLIM7 expression (p = 0.005). In conclusion, we found associations between several genes and hip geometry measures that explained 12% to 22% of heritability at different sites. The results provide a defined set of genes related to biological pathways relevant to BMD and etiology of bone fragility. (c) 2019 American Society for Bone and Mineral Research.
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| 69. |
- Hughes, Derralynn, et al.
(författare)
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Gaucher Disease in Bone : From Pathophysiology To Practice
- 2019
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Ingår i: Journal of Bone and Mineral Research. - : Wiley. - 0884-0431 .- 1523-4681. ; 34:6, s. 996-1013
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Forskningsöversikt (refereegranskat)abstract
- Gaucher disease (GD) is a rare, genetic lysosomal disorder leading to lipid accumulation and dysfunction in multiple organs. Involvement of the skeleton is one of the most prevalent aspects of GD and a major cause of pain, disability, and reduced quality of life. Uniform recommendations for contemporary evaluation and management are needed. To develop practical clinical recommendations, an international group of experienced physicians conducted a comprehensive review of 20 years' of the literature, defining terms according to pathophysiological understanding and pointing out best practice and unmet needs related to the skeletal features of this disorder. Abnormalities of bone modeling, reduced bone density, bone infarction, and plasma cell dyscrasias accompany the displacement of healthy adipocytes in adult marrow. Exposure to excess bioactive glycosphingolipids appears to affect hematopoiesis and the balance of osteoblast and osteoclast numbers and activity. Imbalance between bone formation and breakdown induces disordered trabecular and cortical bone modeling, cortical bone thinning, fragility fractures, and osteolytic lesions. Regular assessment of bone mineral density, marrow infiltration, the axial skeleton and searching for potential malignancy are recommended. MRI is valuable for monitoring skeletal involvement: It provides semiquantitative assessment of marrow infiltration and the degree of bone infarction. When MRI is not available, monitoring of painful acute bone crises and osteonecrosis by plain X-ray has limited value. In adult patients, we recommend DXA of the lumbar spine and left and right hips, with careful protocols designed to exclude focal disease; serial follow-up should be done using the same standardized instrument. Skeletal health may be improved by common measures, including adequate calcium and vitamin D and management of pain and orthopedic complications. Prompt initiation of specific therapy for GD is crucial to optimizing outcomes and preventing irreversible skeletal complications. Investing in safe, clinically useful, and better predictive methods for determining bone integrity and fracture risk remains a need.
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| 70. |
- Iseri, K, et al.
(författare)
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Incidence of Fractures Before and After Dialysis Initiation
- 2020
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Ingår i: Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. - : Wiley. - 1523-4681. ; 35:12, s. 2372-2380
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Tidskriftsartikel (refereegranskat)
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