| 1. |
- Bojan, Alicja J., 1980, et al.
(författare)
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A new bone adhesive candidate- does it work in human bone? An ex-vivo preclinical evaluation in fresh human osteoporotic femoral head bone
- 2022
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Ingår i: Injury-International Journal of the Care of the Injured. - : Elsevier BV. - 0020-1383 .- 1879-0267. ; 53:6, s. 1858-1866
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: The fixation of small intraarticular bone fragments is clinically challenging and an obvious first orthopaedic indication for an effective bone adhesive. In the present study the feasibility of bonding freshly harvested human trabecular bone with OsStic(R), a novel phosphoserine modified cement, was evaluated using a bone cylinder model pull-out test and compared with a commercial fibrin tissue adhesive. Methods: Femoral heads (n=13) were collected from hip fracture patients undergoing arthroplasty and stored refrigerated overnight in saline medium prior to testing. Cylindrical bone cores with a pre-inserted bone screw, were prepared using a coring tool. Each core was removed and glued back in place with either the bone adhesive (alpha-tricalcium phosphate, phosphoserine and 20% trisodium citrate solution) or the fibrin glue. All glued bones were stored in bone medium at 37 degrees C. Tensile loading, using a universal testing machine (5 kN load cell), was applied to each core/head. For the bone adhesive, bone cores were tested at 2 (n=13) and 24 (n=11) hours. For the fibrin tissue adhesive control group (n=9), bone cores were tested exclusively at 2 hours. The femoral bone quality was evaluated with micro-CT. Results: The ultimate pull-out load for the bone adhesive at 2 hours ranged from 36 to 171 N (mean 94 N, SD 42 N). At 24 hours the pull-out strength was similar, 47 to 198 N (mean 123 N, SD 43 N). The adhesive failure usually occurred through the adhesive layer, however in two samples, at 167 N and 198 N the screw pulled out of the bone core. The fibrin tissue adhesive group reached a peak force of 8 N maximally at 2 hours (range 2.8-8 N, mean 5.4 N, SD 1.6 N). The mean BV/TV for femoral heads was 0.15 and indicates poor bone quality. Conclusion: The bone adhesive successfully glued wet and fatty tissue of osteoporotic human bone cores. The mean ultimate pull-out force of 123 N at 24 hours corresponds to similar to 300 kPa shear stress acting on the bone core. These first ex-vivo results in human bone are a promising step toward potential clinical application in osteochondral fragment fixation. (C) 2022 The Authors. Published by Elsevier Ltd.
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| 2. |
- Drevinge, Christina, 1983, et al.
(författare)
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Intermediate monocytes correlate with CXCR3(+) Th17 cells but not with bone characteristics in untreated early rheumatoid arthritis
- 2021
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Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 16:3
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Tidskriftsartikel (refereegranskat)abstract
- Background Rheumatoid arthritis (RA) is associated with development of generalized osteoporosis. Bone-degrading osteoclasts are derived from circulating precursor cells of monocytic lineage, and the intermediate monocyte population is important as osteoclast precursors in inflammatory conditions. T cells of various subsets are critical in the pathogenesis of both RA and associated osteoporosis, but so far, no studies have examined associations between circulating intermediate monocytes, T cell subsets and bone characteristics in patients with RA. The aim of this study was to investigate the frequency of intermediate monocytes in patients with untreated early rheumatoid arthritis (ueRA) compared to healthy controls (HC), and to explore the correlation between intermediate monocytes and a comprehensive panel of T helper cell subsets, bone density and bone microarchitecture in ueRA patients. Methods 78 patients with ueRA fulfilling the ACR/EULAR 2010 criteria were included and compared to 29 age- and sex-matched HC. Peripheral blood samples were obtained before start of treatment and proportions of monocyte subsets and CD4(+) helper and regulatory T cell subsets were analyzed by flow cytometry. Bone densitometry was performed on 46 of the ueRA patients at inclusion using DXA and HR-pQCT. Results Flow cytometric analyses showed that the majority of ueRA patients had frequencies of intermediate monocytes comparable to HC. The intermediate monocyte population correlated positively with CXCR3(+) Th17 cells in ueRA patients but not in HC. However, neither the proportions of intermediate monocytes nor CXCR3(+) Th17 cells were associated with bone density or bone microarchitecture measurements. Conclusions Our findings suggest that in early RA, the intermediate monocytes do not correlate with bone characteristics, despite positive correlation with circulating CXCR3(+) Th17 cells. Future longitudinal studies in patients with longer disease duration are required to fully explore the potential of intermediate monocytes to drive bone loss in RA.
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| 3. |
- Flehr, Alison, et al.
(författare)
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Development of a novel method to measure bone marrow fat fraction in older women using high-resolution peripheral quantitative computed tomography
- 2022
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Ingår i: Osteoporosis International. - : Springer Science and Business Media LLC. - 0937-941X .- 1433-2965. ; 33:7, s. 1545-1556
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Tidskriftsartikel (refereegranskat)abstract
- Bone marrow adipose tissue (BMAT) has been implicated in a number of conditions associated with bone deterioration and osteoporosis. Several studies have found an inverse relationship between BMAT and bone mineral density (BMD), and higher levels of BMAT in those with prevalent fracture. Magnetic resonance imaging (MRI) is the gold standard for measuring BMAT, but its use is limited by high costs and low availability. We hypothesized that BMAT could also be accurately quantified using high-resolution peripheral quantitative computed tomography (HR-pQCT). Methods: In the present study, a novel method to quantify the tibia bone marrow fat fraction, defined by MRI, using HR-pQCT was developed. In total, 38 postmenopausal women (mean [standard deviation] age 75.9 [3.1] years) were included and measured at the same site at the distal (n = 38) and ultradistal (n = 18) tibia using both MRI and HR-pQCT. To adjust for partial volume effects, the HR-pQCT images underwent 0 to 10 layers of voxel peeling to remove voxels adjacent to the bone. Linear regression equations were then tested for different degrees of voxel peeling, using the MRI-derived fat fractions as the dependent variable and the HR-pQCT-derived radiodensity as the independent variables. Results: The most optimal HR-pQCT derived model, which applied a minimum of 4 layers of peeled voxel and with more than 1% remaining marrow volume, was able to explain 76% of the variation in the ultradistal tibia bone marrow fat fraction, measured with MRI (p < 0.001). Conclusion: The novel HR-pQCT method, developed to estimate BMAT, was able to explain a substantial part of the variation in the bone marrow fat fraction and can be used in future studies investigating the role of BMAT in osteoporosis and fracture prediction.
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| 4. |
- Gullberg, Joanna, et al.
(författare)
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The challenge of applying digital image processing software on intraoral radiographs for osteoporosis risk assessment
- 2022
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Ingår i: Dentomaxillofacial Radiology. - : British Institute of Radiology. - 0250-832X .- 1476-542X. ; 51:1
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: The purpose of this study was to evaluate rater agreement and the accuracy of a semi-automated software and its fully automated tool for osteoporosis risk assessment in intraoral radiographs. Methods: A total of 567 intraoral radiographs was selected retrospectively from women aged 75-80 years participating in a large population based study (SUPERB) based in Gothenburg, Sweden. Five raters assessed participants' risk of osteoporosis in the intraoral radiographs using a semi-automated software. Assessments were repeated after 4 weeks on 121 radiographs (20%) randomly selected from the original 567. Radiographs were also assessed by the soft wares' fully automated tool for analysis. Results: Overall interrater agreement for the five raters was 0.37 (95% CI 0.32-0.41), and for the five raters with the fully automated tool included as 'sixth rater' the overall Kappa was 0.34 (0.30-0.38). Intrarater agreement varied from moderate to substantial according to the Landis and Koch interpretation scale. Diagnostic accuracy was calculated in relation to reference standard for osteoporosis diagnosis which is T score values for spine, total hip and femoral neck and presented in form of sensitivities, specificities, predictive values, likelihood ratios and odds ratios. All raters' mean sensitivity, including the fully automated tool, was 40,4% (range 14,3%-57,6%). Corresponding values for specificity was 69,5% (range 59,7%-90,4%). The diagnostic odds ratios ranged between 1 and 2.7. Conclusion: The low diagnostic odds ratio and agreement between raters in osteoporosis risk assessment using the software for analysis of the trabecular pattern in intraoral radiographs shows that more work needs to be done to optimise the automation of trabecular pattern analysis in intraoral radiographs.
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| 5. |
- Gullberg, Joanna, et al.
(författare)
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The outcome of an automated assessment of trabecular pattern in intraoral radiographs as a fracture risk predictor
- 2022
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Ingår i: Dentomaxillofacial Radiology. - : British Institute of Radiology. - 0250-832X .- 1476-542X. ; 51:5
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: This study aims to investigate if automated analyses of the trabecular pattern in intraoral radiographs independently contribute to fracture risk assessment when other risk factors incorporated in the Fracture Risk Assessment Tool (FRAX) are taken into account. A secondary aim is to explore the correlation between the automated trabecular pattern assessment in intraoral radiographs and Trabecular Bone Score (TBS). Methods: A total of 567 intraoral radiographs from older females participating in a large population-based study (SUPERB) based in Gothenburg, Sweden, were selected to analyse trabecular pattern using semi-automated and fully automated software. Associations between trabecular pattern analysis and incident fractures were studied using Cox proportional hazard model, unadjusted and adjusted for FRAX risk factors (previous fracture, family history of hip fracture, smoking, corticosteroids, rheumatoid arthritis, without and with bone mineral density (BMD) of the femoral neck). In addition, the correlation between trabecular pattern analysis and TBS of the lumbar spine was investigated using Pearson correlation analysis. Results: Neither the unadjusted nor the adjusted trabecular pattern analysis in intraoral radiographs was significantly associated with any fracture or major osteoporotic fracture (MOF). A weak correlation was found between semi-automated trabecular pattern analysis and TBS. No correlation was found between the fully automated trabecular pattern analysis and TBS. Conclusions: The present study shows that semi-automated and fully automated digital analyses of the trabecular pattern in intraoral radiographs do not contribute to fracture risk prediction. Furthermore, the study shows a weak correlation between semi-automated trabecular pattern analysis and TBS.
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| 6. |
- Jaiswal, Raju, et al.
(författare)
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Increased Bone Material Strength Index Is Positively Associated With the Risk of Incident Osteoporotic Fractures in Older Swedish Women
- 2023
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Ingår i: Journal of Bone and Mineral Research. - 0884-0431. ; 38:6, s. 860-868
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Tidskriftsartikel (refereegranskat)abstract
- No previous studies have investigated the association between the bone material strength index (BMSi; an indicator of bone material properties obtained by microindentation) and the risk of incident fracture. The primary purpose of this prospective cohort study was to evaluate if BMSi is associated with incident osteoporotic fracture in older women and, secondarily, with prevalent fractures, anthropometric traits, or measurements of bone mineral density (BMD) by dual-energy X-ray absorptiometry (DXA). In a population-based cohort, 647 women aged 75 to 80 years underwent bone microindentation using the OsteoProbe device. Data on clinical risk factors (CRFs), prevalent fractures, and incident fractures were collected using questionnaires, medical records, and a regional X-ray archive. BMD and vertebral fracture assessment (VFA) were assessed by DXA (Hologic, Discovery A). Associations between BMSi, anthropometrics, BMD, and prevalent fractures were investigated using correlation and linear and logistic regression. Cox proportional hazards and competing risks analysis by Fine and Gray were used to study the association between BMSi and the risk of fracture and mortality. BMSi was weakly associated with age (r = -0.13, p < 0.001) and BMI (r = -0.21, p < 0.001) and with BMD of lumbar spine (beta = 0.09, p = 0.02) and total hip (beta = 0.08, p = 0.05), but only after adjustments. No significant associations were found between BMSi and prevalent fractures (self-reported and/or VFA identified, n = 332). During a median follow-up time of 6.0 years, 121 major osteoporotic fractures (MOF), 151 any fractures, and 50 deaths occurred. Increasing BMSi (per SD) was associated with increased risk of MOF (hazard ratio [HR] = 1.29, 95% confidence interval [CI] 1.07-1.56), any fracture (HR = 1.29, 95% CI 1.09-1.53), and mortality (HR = 1.44, 95% CI 1.07-1.93). The risk of fracture did not materially change with adjustment for confounders, CRFs, femoral neck BMD, or when considering the competing risk of death. In conclusion, unexpectedly increasing BMSi was associated with greater fracture risk. The clinical relevance and potential mechanisms of this finding require further study. (c) 2023 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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| 7. |
- Johansson, Lena, 1972, et al.
(författare)
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Decreased physical health-related quality of life—a persisting state for older women with clinical vertebral fracture
- 2019
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Ingår i: Osteoporosis International. - London : Springer London. - 0937-941X .- 1433-2965. ; 30:10, s. 1961-1971
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Tidskriftsartikel (refereegranskat)abstract
- In a population-based study of older Swedish women, we investigated if clinical vertebral fracture was associated with lower health-related quality of life (HRQoL) and determined whether the association remained over time. Clinical vertebral fracture was associated with lower HRQoL and the effect persisted for up to 18.9 years.IntroductionVertebral fractures are often associated with back pain and reduced physical function, which might result in isolation and depression. As a result, women with vertebral fractures often have lower health-related quality of life (HRQoL), but during what time frame the decrease lingers is unclear. Therefore, the aim of this study was to investigate if clinical vertebral fracture and hip fracture were associated with lower HRQoL and to determine whether the associations remained over time.MethodsVertebral fracture assessments (VFA) were performed using dual-energy X-ray absorptiometry. Data regarding prior fractures, medications, medical history, and physical activity was collected using a questionnaire. Self-rated physical HRQoL was assessed using the 12-Item Short-Form Health Survey (SF-12). Women with clinical vertebral fractures were divided into tertiles according to time since fracture onset and their HRQoL was compared with non-fractured women.ResultsIn a population-based cross-sectional study of 3028 women aged 77.8 ± 1.63 (mean ± SD), a total of 130 (4.3%) women reported at least one clinical vertebral fracture. Women with a clinical vertebral fracture, divided into tertiles (T1–T3) depending on time since the fracture occurred, had lower HRQoL (T1: 36.3 ± 10.8; T2: 41.0 ± 9.94; and T3:41.6 ± 11.4) than women without fracture (46.2 ± 10.6; p < 0.001). Using linear regression analysis, clinical vertebral fracture was associated with reduced physical HRQoL for up to 18.9 years, independently of covariates (age, height, weight, smoking, prior stroke, mental HRQoL, grip strength, and lumbar spine BMD).ConclusionsClinical vertebral fracture was associated with lower self-rated physical HRQoL, for up to 18.9 years after time of fracture. © 2019, The Author(s).
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| 8. |
- Johansson, Lisa, et al.
(författare)
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Grade 1 Vertebral Fractures Identified by Densitometric Lateral Spine Imaging Predict Incident Major Osteoporotic Fracture Independently of Clinical Risk Factors and Bone Mineral Density in Older Women
- 2020
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Ingår i: Journal of Bone and Mineral Research. - : Wiley. - 0884-0431 .- 1523-4681. ; 35:10, s. 1942-1951
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Tidskriftsartikel (refereegranskat)abstract
- Because prevalent vertebral fracture (VF) is a strong predictor of future fractures, they are important to identify in clinical practice as osteoporosis medications are effective and can be used to reduce fracture risk in postmenopausal women with VF. Lateral spine imaging (LSI) with dual-energy X-ray absorptiometry (DXA) can be used to diagnose VFs accurately but is not widespread in clinical practice. The prognostic value of grade 1 (20% to 25% compression) VFs diagnosed by LSI with DXA has been insufficiently studied. The aim of this study was to determine if grade 1 VF is associated with incident fracture in older women. Sahlgrenska University Hospital Prospective Evaluation of Risk of Bone Fractures (SUPERB) is a population-based study of 3028 older women from Gothenburg, Sweden. Included women were 75 to 80 years of age at baseline, answered questionnaires, and were scanned with DXA (Discovery A, Hologic, Waltham, MA, USA). LSI was used to diagnose VFs, which were classified using the Genant semiquantitative method. Cox regression models were used to estimate the association between VFs at baseline and X-ray-verified incident fractures, with adjustment for confounders. Women with a grade 1 VF (n= 264) or a grade 2-3 VF (n= 349) were compared with women without any fracture (n= 1482). During 3.6 years (median, interquartile range [IQR] 1.5 years) of follow-up, 260 women had any incident fracture and 213 a major osteoporotic fracture (MOF). Women with only grade 1 VF had increased risk of any fracture (hazard ratio [HR] = 1.67; 95% confidence interval [CI] 1.18-2.36) and MOF (HR = 1.86; 95% CI 1.28-2.72). For MOF, this association remained after adjustment for clinical risk factors and femoral neck bone mineral density (BMD). In conclusion, grade 1 VFs were associated with incident MOF, also after adjustment for clinical risk factors and BMD, indicating that all VF identified by DXA should be considered in the evaluation of fracture risk in older women. (c) 2020 The Authors.Journal of Bone and Mineral Researchpublished by American Society for Bone and Mineral Research..
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| 9. |
- Johansson, Lisa, et al.
(författare)
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The Prevalence of Vertebral Fractures Is Associated With Reduced Hip Bone Density and Inferior Peripheral Appendicular Volumetric Bone Density and Structure in Older Women
- 2018
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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. ; 33:2, s. 250-260
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Tidskriftsartikel (refereegranskat)abstract
- Vertebral fractures (VFs) are among the most severe and prevalent osteoporotic fractures. Their association with bone microstructure have been investigated in several retrospective case-control studies with spine radiography for diagnosis of VF. The aim of this population-based cross-sectional study of 1027 women aged 75 to 80 years was to investigate if prevalent VF, identified by vertebral fracture assessment (VFA) by dual-energy X-ray absorptiometry (DXA), was associated with appendicular volumetric bone density, structure, and bone material strength index (BMSi), independently of hip areal bone mineral density (aBMD). aBMD was measured using DXA (Discovery; Hologic); BMSi with microindentation (Osteoprobe); and bone geometry, volumetric BMD, and microstructure with high-resolution peripheral quantitative computed tomography (HRpQCT) (XtremeCT; Scanco Medical AG). aBMD was lower (spine 3.2%, total hip [TH] 3.8%) at all sites in women with VF, but tibia BMSi did not differ significantly compared to women without VF. In multivariable adjusted logistic regression models, radius trabecular bone volume fraction and tibia cortical area (odds ratio [OR] 1.26; 95% confidence interval [CI], [1.06 to 1.49]; and OR 1.27 [95% CI, 1.08 to 1.49], respectively) were associated with VF prevalence, whereas BMSi and cortical porosity were not. The risk of having one, two, or more than two VFs was increased 1.27 (95% CI, 1.04 to 1.54), 1.83 (95% CI, 1.28 to 2.61), and 1.78 (95% CI, 1.03 to 3.09) times, respectively, for each SD decrease in TH aBMD. When including either cortical area, trabecular bone volume fraction or TBS in the model together with TH aBMD and covariates, only TH aBMD remained independently associated with presence of any VF. In conclusion, TH aBMD was consistently associated with prevalent VFA-verified VF, whereas neither trabecular bone volume fraction, cortical area, cortical porosity, nor BMSi were independently associated with VF in older women. © 2017 American Society for Bone and Mineral Research.
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| 10. |
- Johansson, Lisa, et al.
(författare)
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Vertebral fractures and their association with health-related quality of life, back pain and physical function in older women.
- 2018
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Ingår i: Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA. - : Springer Science and Business Media LLC. - 1433-2965. ; 29:1, s. 89-99
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Tidskriftsartikel (refereegranskat)abstract
- Studies investigating prevalent vertebral fracture (VF) diagnosed using densitometry-based VF assessment (VFA) and associations with physical function, assessed by performance-based measures, are lacking. In this population-based study of 1027 older women, we found that prevalent VF, identified by VFA, was associated with inferior physical health, back pain and inferior physical function.Several studies have investigated the associations between health-related quality of life (HRQL) and back pain with prevalent VF, detected by spine radiographs, but just a few have been population-based and have used vertebral fracture assessment (VFA) for diagnosing VF. The aims of this study were to investigate associations between prevalent VF, detected by VFA, with HRQL, back pain and physical function, and investigate if also mild VFs were associated with these clinical parameters.One thousand twenty-seven women aged 75-80years participated in this population-based cross-sectional study. VF was identified by VFA using dual-energy X-ray absorptiometry. HRQL was assessed by SF-12, back pain during the past 12months using a questionnaire, and physical function was tested with one leg standing (OLS), Timed Up and Go (TUG), walking speed, 30-s chair stand test and maximum grip strength.Physical health (Physical Component Summary, PCS), derived from SF-12, was worse (43.5±11.3 vs. 46.2±10.5, p<0.001) and back pain more frequent in women with any VF than in women without (69.0 vs. 59.9%, p=0.008). PCS and physical function (OLS, 30-s chair stand test), were significantly worse for mild VF compared to no VF (43.8±10.9 vs. 46.2±10.5, p<0.001, 12.7±9.9 vs. 15.3±10.4s, p=0.038, 10.7±3.2 vs. 11.4±3.4 times, p=0.021, respectively). In multivariable adjusted linear regression models, VF prevalence was associated with PCS (β=-0.079, p=0.007), TUG (β=0.067, p=0.021), walking speed (β=-0.071, p=0.009) and 30-s chair stand test (β=-0.075, p=0.012).In conclusion, prevalent VF, diagnosed by VFA, was associated with inferior physical health, back pain and inferior physical function, indicating VFA is useful for diagnosing clinically relevant vertebral fractures. Also, mild VF was associated with inferior physical health and inferior physical function.
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| 11. |
- Khan, Muhammad Tanweer, et al.
(författare)
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Synergy and oxygen adaptation for development of next-generation probiotics
- 2023
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Ingår i: Nature. - 0028-0836. ; 620:7973
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Tidskriftsartikel (refereegranskat)abstract
- The human gut microbiota has gained interest as an environmental factor that may contribute to health or disease(1). The development of next-generation probiotics is a promising strategy to modulate the gut microbiota and improve human health; however, several key candidate next-generation probiotics are strictly anaerobic(2) and may require synergy with other bacteria for optimal growth. Faecalibacterium prausnitzii is a highly prevalent and abundant human gut bacterium associated with human health, but it has not yet been developed into probiotic formulations(2). Here we describe the co-isolation of F. prausnitzii and Desulfovibrio piger, a sulfate-reducing bacterium, and their cross-feeding for growth and butyrate production. To produce a next-generation probiotic formulation, we adapted F. prausnitzii to tolerate oxygen exposure, and, in proof-of-concept studies, we demonstrate that the symbiotic product is tolerated by mice and humans (ClinicalTrials.gov identifier: ) and is detected in the human gut in a subset of study participants. Our study describes a technology for the production of next-generation probiotics based on the adaptation of strictly anaerobic bacteria to tolerate oxygen exposures without a reduction in potential beneficial properties. Our technology may be used for the development of other strictly anaerobic strains as next-generation probiotics.
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| 12. |
- Kristjansdottir, Hallgerdur Lind, et al.
(författare)
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High Serum Serotonin Predicts Increased Risk for Hip Fracture and Nonvertebral Osteoporotic Fractures : The MrOS Sweden Study
- 2018
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Ingår i: Journal of Bone and Mineral Research. - : Wiley. - 0884-0431. ; 33:9, s. 1560-1567
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Tidskriftsartikel (refereegranskat)abstract
- Because several studies have implicated serotonin as a regulator of bone mass, we here explore its potential association on fracture risk and falls, as on bone mineral density (BMD) and muscle strength, in humans. Serum levels of serotonin were analyzed in 950 men (aged 69 to 81 years), participating in the Gothenburg part of the population-based study MrOS Sweden. Men taking selective serotonin reuptake inhibitors (SSRIs) had a mean value of 31.2 μg/L compared with 159.4 μg/L in those not taking SSRIs. SSRI users were excluded from further analysis. During 10-year follow-up, 224 men exhibited fractures, including 97 nonvertebral osteoporotic fractures (57 hip fractures), and 86 vertebral fractures. Serotonin was associated with hip fracture in linear analysis (hazard ratio [HR] = 1.27, 95% confidence interval [CI] 1.03–1.58) and to all fractures in a nonlinear manner, when quintiles of serotonin was included in quadratic terms (HR = 1.12, 95% CI 1.04–1.21). Men in serotonin quintile 5 had, in multivariable analysis, a HR of 2.30 (95% CI 1.31–4.02) for hip fracture and 1.82 (95% CI 1.17–2.85) for nonvertebral fractures compared with men in quintiles 1 to 4. Men in quintile 1 had, in multivariable analysis, a HR of 1.76 (95% CI 1.03–2.99) for nonvertebral fractures compared with men in quintiles 2 to 4. No association was found with vertebral fractures. Individuals in serotonin quintile 1 had higher prevalence of falls compared with quintiles 2 to 5 (odds ratio = 1.90, 95% CI 1.26–2.87). Serotonin was positively associated with hand-grip strength (r = 0.08, p = 0.02) and inversely with hip BMD (r = −0.10, p = 0.003). To assess the association between SSRIs and falls and fractures, the total MrOS Sweden cohort was examined (n = 3014). SSRI users (n = 90) had increased prevalence of falls (16% versus 33%, p = 0.0001) and increased rate of incident fractures (28.0 versus 44.7 per 1000 person-years, p = 0.018). We present novel data showing that high levels of serotonin predict an increased risk for hip fracture and nonvertebral osteoporotic fractures.
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| 13. |
- Larsson, Berit A M, et al.
(författare)
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Association between cortical bone microstructure and statin use in older women.
- 2019
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Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 104:2, s. 250-7
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Tidskriftsartikel (refereegranskat)abstract
- Treatment with statins has been associated with increased bone mineral density (BMD), but if this association depends on differences in cortical or trabecular volumetric bone microstructure is unknown.The aim of this study was to investigate if treatment with statins is associated with bone microstructure and geometry in older women.Older women were included in a population-based study of 3,028 women (mean age ± SD: 77.8 ± 1.6 years) from the greater Gothenburg area in Sweden. Information regarding medical history, medication and life-style factors was obtained from validated questionnaires.Bone geometry and microstructure were measured at the ultradistal and distal (14%) site of radius and tibia using high-resolution peripheral quantitative computed tomography (HR-pQCT; XtremeCT).The 803 women in the cohort who used statins had higher body weight, worse physical function and more frequently cardiovascular disease and diabetes than nonusers (p<0.05). Statin users had lower cortical porosity (radius 2.2± 1.9 vs. 2.5± 2.0%; tibia 5.2± 2.4 vs. 5.4± 2.5, p=0.01), higher cortical bone density (radius 1008 ± 39.1 vs. 1001 ± 38.4 mg/cm3; tibia 919 ± 42.6 vs. 914 ± 41.5, p<0.01), and greater cortical area (radius 60.5 ± 9.6 vs. 58.6 ± 9.7 mm2; tibia 150.0 ± 23.6 vs. 146.7 ± 23.8, p<0.01) than non-users, also after adjustment for a large number of confounders, including age, weight, smoking, other medications and prevalent diseases.Use of statins was associated with better cortical bone characteristics in older women.
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| 14. |
- Larsson, Berit A M, et al.
(författare)
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Normal Bone Microstructure and Density But Worse Physical Function in Older Women Treated with Selective Serotonin Reuptake Inhibitors, a Cross-Sectional Population-Based Study.
- 2018
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Ingår i: Calcified tissue international. - : Springer Science and Business Media LLC. - 1432-0827 .- 0171-967X. ; 103:3, s. 278-288
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Tidskriftsartikel (refereegranskat)abstract
- Depression in the elderly is today often treated with selective serotonin reuptake inhibitors (SSRIs) because of their favorable adverse effect profile. However, treatment with SSRIs is associated with increased risk of fractures. Whether this increased risk depends on reduced bone strength or increased fall risk due to reduced physical function is not certain. The aim was therefore to investigate if treatment with SSRIs is associated with impaired bone microstructure, bone density, or physical function in older women. From an ongoing population-based study, 1057 women (77.7±1.5years) were included. Validated questionnaires were used to assess information regarding medical history, medications, smoking, mental and physical health, and physical activity. Physical function was measured using clinically used tests: timed up and go, walking speed, grip strength, chair stand test, and one leg standing. Bone mineral density (BMD) was measured at the hip and spine with dual-energy X-ray absorptiometry (Hologic Discovery A). Bone geometry and microstructure were measured at the ultradistal and distal (14%) site of radius and tibia using high-resolution peripheral quantitative computed tomography (HR-pQCT; XtremeCT). Treatment with SSRIs was associated with higher BMD at the femoral neck, total hip, and lumbar spine, whereas no associations were found for any HR-pQCT-derived measurements. The use of SSRIs was associated with lower grip strength, walking speed, and fewer chair stand rises. These associations were valid also after adjustments for known risk factors for falls. Treatment with SSRIs was, independently of covariates, associated with worse physical function without any signs of inferior bone geometry and microstructure.
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| 15. |
- Larsson, Berit A M, et al.
(författare)
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One leg standing time predicts fracture risk in older women independent of clinical risk factors and BMD
- 2022
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Ingår i: Osteoporosis International. - : Springer Science and Business Media LLC. - 0937-941X .- 1433-2965. ; 33, s. 185-194
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Tidskriftsartikel (refereegranskat)abstract
- In women of ages 75-80 years, a low one leg standing time (OLST) was associated with an increased risk of incident fractures, independently of bone mineral density and clinical risk factors. OLST contributed substantially to fracture probability, indicating that the test should be considered when evaluating fracture risk in older women. Introduction Physical function and risk of falls are important risk factors for fracture. A few previous studies have suggested that a one leg standing time (OLST) less than 10 s predicts fracture risk, but the impact of OLST, in addition to known clinical risk factors, for fracture probability is unknown. The aim of this study was to determine the independent contribution of OLST to fracture probability in older women. Methods The Sahlgrenska University Hospital Prospective Evaluation of Risk of Bone Fractures (SUPERB) is a prospective population-based study of 3028 women 75-80 years old, recruited from the greater Gothenburg area in Sweden. At baseline, information on risk factors was collected using questionnaires, bone mineral density was measured with dual-energy X-ray absorptiometry (DXA), and OLST was performed. Results During a median follow-up of 3.6 years (IQR 1.5 years), X-ray-verified incident fractures were identified using health records. OLST was available in 2405 women. OLST less than 10 s was associated with an increased risk for incident hip fracture (Hazard Ratio (HR) 3.02, 95% Confidence Interval (CI) [1.49-6.10]), major osteoporotic fracture (HR 95% CI 1.76 [1.34-1.46]), and nonvertebral fracture (HR 95% CI 1.61 [1.26-2.05]) in Cox regression analyses adjusted for age, height, and weight. Depending on BMD, the 4-year fracture probability increased by a factor of 1.3 to 1.5 in a 75-year-old woman with a low OLST (<10 s). Conclusion A low OLST has a substantial impact on fracture probability and should be considered when evaluating fracture risk in older women.
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| 16. |
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| 17. |
- Larsson, B. A. M., et al.
(författare)
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The timed up and go test predicts fracture risk in older women independently of clinical risk factors and bone mineral density
- 2021
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Ingår i: Osteoporosis International. - : SPRINGER LONDON LTD. - 0937-941X .- 1433-2965. ; 32, s. 75-84
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Tidskriftsartikel (refereegranskat)abstract
- The timed up and go (TUG) test measures physical performance and predicts falls in the elderly. In older women, TUG time predicts the risk of major osteoporotic fracture and hip fracture independently of clinical risk factors and bone mineral density, and has a substantial impact on fracture probabilities. Introduction The timed up and go (TUG) test measures physical performance and predicts falls in the elderly. A slow TUG has been associated with an increased fracture risk, but it is unclear whether the association is independent of clinical risk factors and bone mineral density (BMD). The aim of this study was to investigate if TUG time was associated with fracture risk independently of clinical risk factors and BMD and to determine its impact on fracture probabilities in older women. Methods A standardized questionnaire was used to assess information regarding clinical risk factors in the large population-based SUPERB study of 3028 older women (75-80 years). At baseline, the TUG test was performed and BMD measured with DXA. The association between TUG time and the risk of hip fracture and major osteoporotic fracture (MOF) was examined using an extension of Poisson regression. Results Fracture incidence increased steeply with increasing TUG time up to 12 s and subsequently started to level off. A slow TUG time was therefore defined as TUG > 12 s, a cutoff level then used in Cox models to study the association between slow TUG and fracture risk. A slow TUG time was associated with an increased risk of fracture (MOF 2.39 [1.80-3.18] and hip fracture 2.96 [1.62-5.40]). These associations were slightly attenuated but remained significant after adjustment for clinical risk factors and femoral neck BMD. Depending on BMD, the 4-year fracture probability of MOF increased by a factor of 1.5-1.9 in a 75-year-old woman with slow TUG (> 12 s). Conclusion The TUG time predicts the risk of MOF and hip fracture independently of clinical risk factors and BMD and has a substantial impact on fracture probabilities, indicating that inclusion of the TUG test in patient evaluation should be considered in order to improve fracture prediction in older women.
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| 18. |
- Li, Peishun, 1988, et al.
(författare)
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Metabolic Alterations in Older Women With Low Bone Mineral Density Supplemented With Lactobacillus reuteri
- 2021
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Ingår i: JBMR Plus. - : Wiley. - 2473-4039. ; 5:4
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Tidskriftsartikel (refereegranskat)abstract
- JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research. Osteoporosis and its associated fractures are highly prevalent in older women. Recent studies have shown that gut microbiota play important roles in regulating bone metabolism. A previous randomized controlled trial (RCT) found that supplementation with Lactobacillus reuteri ATCC PTA 6475 (L.reuteri) led to substantially reduced bone loss in older women with low BMD. However, the total metabolic effects of L. reuteri supplementation on older women are still not clear. In this study, a post hoc analysis (not predefined) of serum metabolomic profiles of older women from the previous RCT was performed to investigate the metabolic dynamics over 1 year and to evaluate the effects of L. reuteri supplementation on human metabolism. Distinct segregation of the L. reuteri and placebo groups in response to the treatment was revealed by partial least squares-discriminant analysis. Although no individual metabolite was differentially and significantly associated with treatment after correction for multiple testing, 97 metabolites responded differentially at any one time point between L. reuteri and placebo groups (variable importance in projection score >1 and p value <0.05). These metabolites were involved in multiple processes, including amino acid, peptide, and lipid metabolism. Butyrylcarnitine was particularly increased at all investigated time points in the L. reuteri group compared with placebo, indicating that the effects of L. reuteri on bone loss are mediated through butyrate signaling. Furthermore, the metabolomic profiles in a case (low BMD) and control population (high BMD) of elderly women were analyzed to confirm the associations between BMD and the identified metabolites regulated by L. reuteri supplementation. The amino acids, especially branched-chain amino acids, showed association with L. reuteri treatment and with low BMD in older women, and may serve as potential therapeutic targets. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.
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| 19. |
- Li, Peishun, 1988, et al.
(författare)
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One-year supplementation with Lactobacillus reuteri ATCC PTA 6475 counteracts a degradation of gut microbiota in older women with low bone mineral density
- 2022
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Ingår i: npj Biofilms and Microbiomes. - : Springer Science and Business Media LLC. - 2055-5008. ; 8:1
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Tidskriftsartikel (refereegranskat)abstract
- Recent studies have shown that probiotic supplementation has beneficial effects on bone metabolism. In a randomized controlled trial (RCT) we demonstrated that supplementation of Lactobacillus reuteri ATCC PTA 6475 reduced bone loss in older women with low bone mineral density. To investigate the mechanisms underlying the effect of L. reuteri ATCC PTA 6475 on bone metabolism, 20 women with the highest changes (good responders) and the lowest changes (poor responders) in tibia total volumetric BMD after one-year supplementation were selected from our previous RCT. In the current study we characterized the gut microbiome composition and function as well as serum metabolome in good responders and poor responders to the probiotic treatment as a secondary analysis. Although there were no significant differences in the microbial composition at high taxonomic levels, gene richness of the gut microbiota was significantly higher (P < 0.01 by the Wilcoxon rank-sum test) and inflammatory state was improved (P < 0.05 by the Wilcoxon signed-rank test) in the good responders at the end of the 12-month daily supplementation. Moreover, detrimental changes including the enrichment of E. coli (adjusted P < 0.05 by DESeq2) and its biofilm formation (P < 0.05 by GSA) observed in the poor responders were alleviated in the good responders by the treatment. Our results indicate that L. reuteri ATCC PTA 6475 supplementation has the potential to prevent a deterioration of the gut microbiota and inflammatory status in elderly women with low bone mineral density, which might have beneficial effects on bone metabolism.
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| 20. |
- Liu, D. C., et al.
(författare)
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The Human Stratum Corneum Prevents Small Gold Nanoparticle Penetration and Their Potential Toxic Metabolic Consequences
- 2012
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Ingår i: Journal of Nanomaterials. - : Hindawi Limited. - 1687-4110 .- 1687-4129.
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Tidskriftsartikel (refereegranskat)abstract
- Nanoparticles are being used inmultiple applications, ranging from biomedical and skin care products (e. g., sunscreen) through to industrial manufacturing processes (e. g., water purification). The increase in exposure has led to multiple reports on nanoparticle penetration and toxicity. However, the correlation between nanoparticle size and its penetration without physical/chemical enhancers through the skin is poorly understood-with studies instead focusing primarily on skin penetration under disrupted conditions. In this paper, we investigate the penetration and metabolic effects of 10 nm, 30 nm, and 60 nm gold nanoparticles within viable excised human skin after 24-hour exposure usingmultiphoton tomograph-fluorescence lifetime imaging microscopy. After 24 hour treatment with the 10, 30, and 60 nm gold nanoparticles, there was no significant penetration detected below the stratum corneum. Furthermore, there were no changes in metabolic output (total NAD(P) H) in the viable epidermis posttreatment correlating with lack of penetration of nanoparticles. These results are significant for estimating topical nanoparticle exposure in humans where other model systems may overestimate the exposure of nanoparticles to the viable epidermis. Our data shows that viable human skin resists permeation of small nanoparticles in a size range that has been reported to penetrate deeply in other skin models.
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| 21. |
- Lorentzon, Mattias, 1970, et al.
(författare)
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Extensive undertreatment of osteoporosis in older Swedish women
- 2019
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Ingår i: Osteoporosis International. - : Springer Science and Business Media LLC. - 0937-941X .- 1433-2965. ; 30:6, s. 1297-1305
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Tidskriftsartikel (refereegranskat)abstract
- Summary: In a population-based study of older Swedish women, we investigated the proportion of women treated with osteoporosis medication in relation to the proportion of women eligible for treatment according to national guidelines. We found that only a minority (22%) of those eligible for treatment were prescribed osteoporosis medication. Introduction: Fracture rates increase markedly in old age and the incidence of hip fracture in Swedish women is among the highest in the world. Although effective pharmacological treatment is available, treatment rates remain low. Limited data are available regarding treatment rates in relation to fracture risk in a population-based setting in older women. Therefore, we aimed to investigate the proportion of older women eligible for treatment according to Swedish Osteoporosis Society (SvOS) guidelines. Methods: A population-based study was performed in Gothenburg in 3028 older women (77.8 ± 1.6years [mean ± SD]). Bone mineral density of the spine and hip was measured with dual-energy X-ray absorptiometry. Clinical risk factors for fracture and data regarding osteoporosis medication was collected with self-administered questionnaires. Logistic regression was used to evaluate whether the 10-year probability of sustaining a major osteoporotic fracture (FRAX-score) or its components predicted treatment with osteoporosis medication. Results: For the 2983 women with complete data, 1107 (37%) women were eligible for treatment using SvOS criteria. The proportion of these women receiving treatment was 21.8%. For women eligible for treatment according to SvOS guidelines, strong predictors for receiving osteoporosis medication were glucocorticoid treatment (odds ratio (95% CI) 2.88 (1.80–4.59)) and prior fracture (2.58 (1.84–3.61)). Conclusion: This study demonstrates that a substantial proportion of older Swedish women should be considered for osteoporosis medication given their high fracture risk, but that only a minority receives treatment. © 2019, The Author(s).
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| 22. |
- Nilsson, Anna G, 1968, et al.
(författare)
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Lactobacillus reuteri reduces bone loss in older women with low bone mineral density: a randomized, placebo-controlled, double-blind, clinical trial
- 2018
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Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820. ; 284:3, s. 307-317
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundThe importance of the gut microbiome for bone metabolism in mice has recently been demonstrated, but no studies are available in humans. Lactobacillus reuteri ATCCPTA 6475 (L. reuteri 6475) has been reported to increase bone mineral density (BMD) in mice but its effect on the human skeleton is unknown. The objective of this trial was to investigate if L. reuteri 6475 affects bone loss in older women with low BMD. MethodsIn this double-blind, placebo-controlled study, women from the population who were 75 to 80 years old and had low BMD were randomized to orally receive 10(10) colony-forming units of L. reuteri 6475 daily or placebo. The predefined primary end-point was relative change after 12 months in tibia total volumetric BMD (vBMD). ResultsNinety women were included and 70 completed the study. L. reuteri 6475 reduced loss of total vBMD compared to placebo both in the intention-to-treat (ITT) analysis [-0.83% (95% confidence interval [CI], -1.47 to -0.19%) vs. -1.85% (95% CI, -2.64 to -1.07%); mean difference 1.02% (95% CI, 0.02-2.03)] and per protocol analysis [-0.93% (95% CI, -1.45 to -0.40) vs. -1.86% (95% CI, -2.35 to -1.36); mean difference 0.93% (95% CI, 0.21-1.65)]. In general, similar but smaller effects were observed in the secondary bone variable outcomes, but these differences did not reach statistical significance in the ITT population. Adverse events did not differ between groups. ConclusionsSupplementation with L. reuteri 6475 should be further explored as a novel approach to prevent age-associated bone loss and osteoporosis.
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| 23. |
- Nilsson, Anna G, 1968, et al.
(författare)
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Type 2 Diabetes Mellitus is Associated with Better Bone Microarchitecture But Lower Bone Material Strength and Poorer Physical Function in Elderly Women - a Population-Based Study.
- 2017
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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. ; 32:5
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Tidskriftsartikel (refereegranskat)abstract
- Type 2 diabetes mellitus (T2DM) is associated with an increased risk of fractures according to several studies. The underlying mechanisms remain unclear, although small case-control studies indicate poor quality of the cortical bone. We have studied a population-based sample of women aged 75-80 in Gothenburg, randomly invited from the population registry. Areal bone mineral density (aBMD) was measured by dual energy x-ray absorptiometry (Hologic Discovery A), bone microarchitecture by high-resolution peripheral quantitative computed tomography (HR-pQCT; ExtremeCT from Scanco Medical AG), and reference point indentation was performed with Osteoprobe (Active Life Scientific). Women with T2DM (n=99) had higher aBMD compared to controls (n=954). Ultradistal tibial and radial trabecular bone volume fraction (+11% and +15%, respectively), distal cortical volumetric BMD (+1.6% and +1.7%), cortical area (+11.5% and +9.3%), and failure load (+7.7% and +12.9%) were higher in diabetics than in controls. Cortical porosity was lower (mean±SD: 1.5±1.1 vs 2.0±1.7%, p=0.001) in T2DM in the distal radius but not in the ultradistal radius or the tibia. Adjustment for covariates (age, body mass index, glucocorticoid treatment, smoking, physical activity, calcium intake, bone-active drugs) eliminated the differences in aBMD but not in HR-pQCT bone variables. However, bone material strength index (BMSi) by reference point indentation was lower in T2DM (74.6±7.6 vs 78.2±7.5, p<0.01), also after adjustment, and women with T2DM performed clearly worse in measures of physical function (one leg standing: -26%, 30s chair-stand test: -7%, timed up and go: +12%, walking speed: +8%; p<0.05-0.001) compared to controls. In conclusion, we observed a more favorable bone microarchitecture but no difference in adjusted aBMD in elderly women with T2DM in the population compared to non-diabetics. Reduced BMSi and impaired physical function may explain the increased fracture risk in T2DM. This article is protected by copyright. All rights reserved.
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| 24. |
- Nilsson, Martin, 1966, et al.
(författare)
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Association of physical activity with trabecular microstructure and cortical bone at distal tibia and radius in young adult men
- 2010
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Ingår i: J Clin Endocrinol Metab. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 95:6, s. 2917-26
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Tidskriftsartikel (refereegranskat)abstract
- CONTEXT: The relationship between physical activity, trabecular microstructure, and cortical geometry in weight-bearing and non-weight-bearing bone has not previously been studied in men. OBJECTIVE: The aim of this study was to investigate whether present (type and amount) and previous duration of physical activity were associated with trabecular microstructure and cortical cross-sectional area (CSA) in weight-bearing bone in young men. DESIGN AND SETTING: This was a cross-sectional, population-based study. PARTICIPANTS: Participants included a cohort of 829 Swedish men between 22.8 and 25.7 yr old (24.1 +/- 0.6 yr, mean +/- SD). MAIN OUTCOME MEASURES: Several microstructural trabecular and cortical traits were assessed with high-resolution three-dimensional peripheral quantitative computed tomography at distal tibia and radius. A standardized questionnaire was used to collect information about physical activity amount (hours per year), duration (years), and type (strain score 0-3, based on ground reaction forces). RESULTS: Men with the highest physical activity strain score had higher tibial trabecular bone volume fraction (13.9Delta%) and trabecular number (12.7%) than men with the lowest strain score (P < 0.001). Men in the group with the longest duration of physical activity had higher tibial cortical CSA (16.1%) than the sedentary men (P < 0.001). Inclusion of all physical activity variables in a linear regression model revealed that strain score independently predicted trabecular bone volume fraction, and trabecular number (P < 0.001) and that duration of previous physical activity independently predicted cortical CSA (P < 0.001) of the tibia. CONCLUSIONS: In this large cohort of young men, the degree of mechanical loading due to type of physical activity was predominantly associated with trabecular microstructure, whereas duration of previous physical activity was mainly related to parameters reflecting cortical bone size in weight-bearing bone.
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| 25. |
- Nilsson, Martin, 1966, et al.
(författare)
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Current Physical Activity Is Independently Associated With Cortical Bone Size and Bone Strength in Elderly Swedish Women.
- 2017
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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. ; 32:3, s. 473-485
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Tidskriftsartikel (refereegranskat)abstract
- Physical activity is believed to have the greatest effect on the skeleton if exerted early in life, but whether or not possible benefits of physical activity on bone microstructure or geometry remain at old age has not been investigated in women. The aim of this study was to investigate if physical activity during skeletal growth and young adulthood or at old age was associated with cortical geometry and trabecular microarchitecture in weight-bearing and non-weight-bearing bone, and areal bone mineral density (aBMD) in elderly women. In this population-based cross-sectional study 1013 women, 78.2±1.6 (mean±SD) years old, were included. Using high-resolution 3D pQCT (XtremeCT), cortical cross-sectional area (Ct.CSA), cortical thickness (Ct.Th), cortical periosteal perimeter (Ct.Pm), volumetric cortical bone density (D.Ct), trabecular bone volume fraction (BV/TV), trabecular number (Tb.N), trabecular thickness (Tb.Th), and trabecular separation (Tb.Sp) were measured at the distal (14% level) and ultra-distal tibia and radius, respectively. aBMD was assessed using DXA (Hologic Discovery A) of the spine and hip. A standardized questionnaire was used to collect information about previous exercise and the Physical Activity Scale for the Elderly (PASE) was used for current physical activity. A linear regression model (including levels of exercise during skeletal growth and young adulthood [10 to 30 years of age], PASE score, and covariates) revealed that level of current physical activity was independently associated with Ct.CSA (β=0.18, p<0.001) and Ct.Th (β=0.15, p<0.001) at the distal tibia, Tb.Th (β=0.11, p<0.001) and BV/TV (β=0.10, p=0.001) at the ultra-distal tibia, and total hip aBMD (β=0.10, p<0.001). Current physical activity was independently associated with cortical bone size, in terms of thicker cortex but not larger periosteal circumference, and higher bone strength at the distal tibia on elderly women, indicating that physical activity at old age may decrease cortical bone loss in weight-bearing bone in elderly women. © 2016 American Society for Bone and Mineral Research.
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