| 1. |
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| 2. |
- Alfvén, Tobias, et al.
(author)
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Low-level cadmium exposure and osteoporosis.
- 2000
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In: Journal of Bone and Mineral Research. - 0884-0431 .- 1523-4681. ; 15, s. 1579-1586
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Journal article (peer-reviewed)abstract
- Osteoporosis is a major cause of morbidity worldwide. A number of risk factors, such as age and gender, are well established. High cadmium exposure causes renal damage and in severe cases also causes osteoporosis and osteomalacia, We have examined whether long-term Pow-level cadmium exposure increases the risk of osteoporosis. Bone mineral density (BMD) in the forearm was measured in 520 men and 544 women, aged 16-81 years, environmentally or occupationally exposed to cadmium, using dual-energy X-ray absorptiometry (DXA) technique. Cadmium in urine was used as the dose estimate and protein HC was used: as a marker of renal tubular damage. There was a clear dose-response relation between cadmium dose and the prevalence of tubular proteinuria. Inverse relations were found between cadmium dose, tubular proteinuria, and BMD, particularly apparent in persons over 60 years of age, There was a dose-response relation between cadmium dose and osteoporosis. The odds ratios (ORs) for men were 2.2 (95% CI, 1.0-4.8) in the dose group 0.5-3 nmol Cd/mmol creatinine and 5.3 (2.0-14) in the highest dose category (greater than or equal to 3 nmol/mmol creatinine) compared with the lowest dose group (<0.5 nmol Cd/mmol creatinine). For women, the OR was 1.8 (0.65-5.3) in the dose group 0.53 nmol Cd/mmol creatinine. We conclude that exposure to low levels of cadmium is associated with an increased risk of osteoporosis.
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| 3. |
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| 4. |
- Aspenberg, Per, et al.
(author)
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Teriparatide for Acceleration of Fracture Repair in Humans: A Prospective, Randomized, Double-Blind Study of 102 Postmenopausal Women With Distal Radial Fractures
- 2010
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In: JOURNAL OF BONE AND MINERAL RESEARCH. - : Wiley. - 0884-0431 .- 1523-4681. ; 25:2, s. 404-414
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Journal article (peer-reviewed)abstract
- Animal experiments show a dramatic improvement in skeletal repair by teriparatide. We tested the hypothesis that recombinant teriparatide, at the 20 mu g dose normally used for osteoporosis treatment or higher, would accelerate fracture repair in humans. Postmenopausal women (45 to 85 years of age) who had sustained a dorsally angulated distal radial fracture in need of closed reduction but no surgery were randomly assigned to 8 weeks of once-daily injections of placebo (n = 34) or teriparatide 20 mu g (n = 34) or teriparatide 40 mu g (n = 34) within 10 days of fracture. Hypotheses were tested sequentially, beginning with the teriparaticle 40 mu g versus placebo comparison, using a gatekeeping strategy. The estimated median time from fracture to first radiographic evidence of complete cortical bridging in three of four cortices was 9.1, 7.4, and 8.8 weeks for placebo and teriparaticle 20 1 and 40 mu g, respectively (overall p = .015). There was no significant difference between the teriparaticle 40 mu g versus placebo groups (p = .523). In post hoc analyses, there was no significant difference between teriparaticle 40 1 versus 20 mu g (p = .053); however, the time to healing was shorter in teriparaticle 20 mu g than placebo (p = .006). The primary hypothesis that teriparatide 40 jug would shorten the time to cortical bridging was not supported. The shortened time to healing for teriparaticle 20 mu g compared with placebo still may suggest that fracture repair can be accelerated by teriparaticle, but this result should be interpreted with caution and warrants further study.
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| 5. |
- Aspenberg, Per, et al.
(author)
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The bone morphogenetic proteins antagonist noggin inhibits membranous ossification
- 2001
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In: Journal of Bone and Mineral Research. - : Wiley. - 1523-4681 .- 0884-0431. ; 16:3, s. 497-500
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Journal article (peer-reviewed)abstract
- Bone morphogenetic proteins (BMPs) are expressed and secreted during fracture repair. Although they are likely to be required for this process, little is known about their physiological role in bone regeneration. Noggin is a protein that specifically binds and inactivates several BMPs, It plays fundamental roles during early embryonal development and limb morphogenesis by this BMP-inactivating activity. This study shows that Noggin can modify bone formation in vivo in the adult animal and, thus, indirectly, that BMP signaling is indispensable in this process. A noggin mutein (hNg Delta B2-Fc) engineered so as to display increased bioavailability was used. Bilateral titanium bone chambers mere inserted in 70 rats, and side comparisons for bone formation in the chambers were done. The hNg Delta B2-Fc had no effect on total amount of tissue formed in the chamber but decreased the amount of bone compared with both buffer controls and a control made up of an Fc-tagged IL-6R alpha protein, which had no effects of its own, Also, wild-type noggin inhibited bone formation. Thus, endogenous BMP signaling is necessary for normal bone regeneration.
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| 6. |
- Axelsson, Kristian F., et al.
(author)
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Association Between Recurrent Fracture Risk and Implementation of Fracture Liaison Services in Four Swedish Hospitals: A Cohort Study
- 2020
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In: Journal of Bone and Mineral Research. - : Wiley. - 0884-0431 .- 1523-4681. ; 35:7, s. 1216-1223
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Journal article (peer-reviewed)abstract
- © 2020 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research Structured secondary preventions programs, called fracture liaison services (FLSs), increase the rate of evaluation with bone densitometry and use of osteoporosis medication after fracture. However, the evidence regarding the effect on the risk of recurrent fracture is insufficient. The aim of this study was to investigate if implementation of FLS was associated with reduced risk of recurrent fractures. In this retrospective cohort study, electronic health records during 2012 to 2017 were used to identify a total of 21,083 patients from four hospitals in Western Sweden, two with FLS (n = 15,449) and two without (n = 5634). All patients aged 50 years or older (mean age 73.9 [SD 12.4] years, 76% women) with a major osteoporotic index fracture (hip, clinical spine, humerus, radius, and pelvis) were included. The primary outcome was recurrent major osteoporotic fracture. All patients with an index fracture during the FLS period (n = 13,946) were compared with all patients in the period before FLS implementation (n = 7137) in an intention-to-treat analysis. Time periods corresponding to the FLS hospitals were used for the non-FLS hospitals. In the hospitals with FLSs, there were 1247 recurrent fractures during a median follow-up time of 2.2 years (range 0–6 years). In an unadjusted Cox model, the risk of recurrent fracture was 18% lower in the FLS period compared with the control period (hazard ratio = 0.82, 95% confidence interval [CI] 0.73–0.92, p = 0.001), corresponding to a 3-year number needed to screen of 61, and did not change after adjustment for clinical risk factors. In the hospitals without FLSs, no change in recurrent fracture rate was observed. Treatment decisions were made according to the Swedish treatment guidelines. In conclusion, implementation of FLS was associated with a reduced risk of recurrent fracture, indicating that FLSs should be included routinely at hospitals treating fracture patients. © 2020 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research.
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| 7. |
- Axelsson, Kristian F, et al.
(author)
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Fracture risk after gastric bypass surgery – a retrospective cohort study
- 2018
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In: Journal of Bone and Mineral Research. - : Wiley-Blackwell Publishing Inc.. - 0884-0431 .- 1523-4681. ; 33:12, s. 2122-2131
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Journal article (peer-reviewed)abstract
- Gastric bypass surgery constitutes the most common and effective bariatric surgery to treat obesity. Gastric bypass leads to bone loss, but fracture risk following surgery has been insufficiently studied. Furthermore, the association between gastric bypass and fracture risk has not been studied in patients with diabetes, which is a risk factor for fracture and affected by surgery. In this retrospective cohort study using Swedish national databases, 38 971 obese patients undergoing gastric bypass were identified, 7758 with diabetes and 31 213 without. An equal amount of well-balanced controls were identified through multivariable 1:1 propensity score matching. The risk of fracture and fall injury was investigated using Cox proportional hazards and flexible parameter models. Fracture risk according to weight loss and degree of calcium and vitamin D supplementation one-year post- surgery was investigated. During a median follow-up time of 3.1 (IQR 1.7-4.6) years, gastric bypass was associated with increased risk of any fracture, in patients with and without diabetes using a multivariable Cox model (HR 1.26, 95% CI 1.05- 1.53 and HR 1.32, 95% CI 1.18-1.47, respectively). Using flexible parameter models, the fracture risk appeared to increase with time. The risk of fall injury without fracture was also increased after gastric bypass. Larger weight loss or poor calcium and vitamin D supplementation after surgery were not associated with increased fracture risk. In conclusion, gastric bypass surgery is associated with an increased fracture risk, which appears to be increasing with time and not associated with degree of weight loss or calcium and vitamin D supplementation following surgery. An increased risk of fall injury was seen after surgery, which could contribute to the increased fracture risk. This article is protected by copyright. All rights reserved.
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| 8. |
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| 9. |
- Axelsson, Kristian F, 1973, et al.
(author)
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The Importance of Recent Prevalent Fracture Site for Imminent Risk of Fracture - A Retrospective, Nationwide Cohort Study of Older Swedish Men and Women
- 2023
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In: Journal of Bone and Mineral Research. - : Wiley. - 0884-0431 .- 1523-4681. ; 38:6, s. 851-859
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Journal article (peer-reviewed)abstract
- There is limited evidence regarding which fracture types carry the highest risk for subsequent fracture. The aim of this study was to investigate how the risk of imminent fracture depends on index fracture site. This nationwide retrospective cohort study utilized national registers in Sweden to determine the risk of fracture according to recent (<= 2 years) index fracture site and according to an old (>2 years) prevalent fracture compared with the risk observed in controls without a fracture. All Swedes 50 years or older between 2007 and 2010 were included in the study. Patients with a recent fracture were designated a specific fracture group depending on the type of previous fracture. Recent fractures were classified as major osteoporotic fracture (MOF), including fractured hip, vertebra, proximal humerus, and wrist, or non-MOF. Patients were followed until December 31, 2017, censored for death and emigration, and the risk of any fracture and hip fracture was assessed. A total of 3,423,320 persons were included in the study, 70,254 with a recent MOF, 75,526 with a recent non-MOF, 293,051 with an old fracture, and 2,984,489 persons with no previous fracture. The median time of follow-up for the four groups was 6.1 (interquartile range [IQR] 3.0-8.8), 7.2 (5.6-9.4), 7.1 (5.8-9.2), and 8.1 years (7.4-9.7), respectively. Patients with a recent MOF, recent non-MOF, and old fracture had a substantially increased risk of any fracture (hazard ratio [HR] adjusted for age and sex 2.11, 95% confidence interval [CI] 2.08-2.14; HR 2.24, 95% CI 2.21-2.27; and HR 1.77, 95% CI 1.76-1.78, respectively) compared with controls. All recent fractures, MOFs, and non-MOFs, as well as older fractures, increase the risk of subsequent fracture, suggesting that all recent fractures should be included in fracture liaison services and that case-finding strategies for those with older fractures may be warranted to prevent subsequent fractures.
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| 10. |
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| 11. |
- Baird, Denis A., et al.
(author)
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Identification of Novel Loci Associated With Hip Shape : A Meta-Analysis of Genomewide Association Studies.
- 2019
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In: Journal of Bone and Mineral Research. - : Wiley-Blackwell. - 0884-0431 .- 1523-4681. ; 34:2, s. 241-251
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Journal article (peer-reviewed)abstract
- We aimed to report the first genomewide association study (GWAS) meta-analysis of dual-energy X-ray absorptiometry (DXA)-derived hip shape, which is thought to be related to the risk of both hip osteoarthritis and hip fracture. Ten hip shape modes (HSMs) were derived by statistical shape modeling using SHAPE software, from hip DXA scans in the Avon Longitudinal Study of Parents and Children (ALSPAC; adult females), TwinsUK (mixed sex), Framingham Osteoporosis Study (FOS; mixed), Osteoporotic Fractures in Men study (MrOS), and Study of Osteoporotic Fractures (SOF; females) (total N = 15,934). Associations were adjusted for age, sex, and ancestry. Five genomewide significant (p < 5 × 10-9 , adjusted for 10 independent outcomes) single-nucleotide polymorphisms (SNPs) were associated with HSM1, and three SNPs with HSM2. One SNP, in high linkage disequilibrium with rs2158915 associated with HSM1, was associated with HSM5 at genomewide significance. In a look-up of previous GWASs, three of the identified SNPs were associated with hip osteoarthritis, one with hip fracture, and five with height. Seven SNPs were within 200 kb of genes involved in endochondral bone formation, namely SOX9, PTHrP, RUNX1, NKX3-2, FGFR4, DICER1, and HHIP. The SNP adjacent to DICER1 also showed osteoblast cis-regulatory activity of GSC, in which mutations have previously been reported to cause hip dysplasia. For three of the lead SNPs, SNPs in high LD (r2 > 0.5) were identified, which intersected with open chromatin sites as detected by ATAC-seq performed on embryonic mouse proximal femora. In conclusion, we identified eight SNPs independently associated with hip shape, most of which were associated with height and/or mapped close to endochondral bone formation genes, consistent with a contribution of processes involved in limb growth to hip shape and pathological sequelae. These findings raise the possibility that genetic studies of hip shape might help in understanding potential pathways involved in hip osteoarthritis and hip fracture. © 2018 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals, Inc.
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| 12. |
- Banefelt, Jonas, et al.
(author)
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Total Hip Bone Mineral Density as an Indicator of Fracture Risk in Bisphosphonate-Treated Patients in a Real-World Setting
- 2022
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In: Journal of Bone and Mineral Research. - : Wiley. - 0884-0431 .- 1523-4681. ; 37:1, s. 52-58
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Journal article (peer-reviewed)abstract
- Bone mineral density (BMD) is an established measure used to diagnose patients with osteoporosis. In clinical trials, change in BMD has been shown to provide a reliable estimate of fracture risk reduction, and achieved BMD T-score has been shown to reflect the near-term risk of fracture. We aimed to test the association between BMD T-score and fracture risk in patients treated for osteoporosis in a real-world setting. This retrospective, observational cohort study included Swedish females aged ≥55 years who had a total hip BMD measurement at one of three participating clinics. Patients were separated into two cohorts: bisphosphonate-treated and bisphosphonate-naïve prior to BMD measurement, stratified by age and prior nonvertebral fracture status. The primary outcome was cumulative incidence of clinical fractures within 24 months of BMD measurement, with other fracture types included as secondary outcomes. Associations between T-score and fracture risk were estimated using proportional hazards regression and restricted cubic splines. A total of 15,395 patients were analyzed: 11,973 bisphosphonate-naïve and 3422 bisphosphonate-treated. In the 24 months following BMD measurement, 6.3% (95% confidence interval [CI], 5.9–6.7) of bisphosphonate-naïve and 8.4% (95% CI, 7.5–9.4) of bisphosphonate-treated patients experienced a clinical fracture. Strong inverse relationships between BMD T-score and fracture incidence were observed in both cohorts. Among bisphosphonate-naïve patients, this relationship appeared to plateau around T-score −1.5, indicating smaller marginal reductions in fracture risk above this value; bisphosphonate-treated patients showed a more consistent marginal change in fracture risk across the evaluated T-scores (−3.0 to –0.5). Trends remained robust regardless of age and prior fracture status. This real-world demonstration of a BMD–fracture risk association in both bisphosphonate-naïve and bisphosphonate-treated patients extends evidence from clinical trials and recent meta-regressions supporting the suitability of total hip BMD as a meaningful outcome for the clinical management of patients with osteoporosis.
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| 13. |
- Batkovskyte, D., et al.
(author)
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Al-Gazali Skeletal Dysplasia Constitutes the Lethal End of ADAMTSL2-Related Disorders
- 2023
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In: Journal of Bone and Mineral Research. - : Wiley. - 0884-0431 .- 1523-4681. ; 38:5, s. 692-706
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Journal article (peer-reviewed)abstract
- Lethal short-limb skeletal dysplasia Al-Gazali type (OMIM %601356), also called dysplastic cortical hyperostosis, Al-Gazali type, is an ultra-rare disorder previously reported in only three unrelated individuals. The genetic etiology for Al-Gazali skeletal dysplasia has up until now been unknown. Through international collaborative efforts involving seven clinical centers worldwide, a cohort of nine patients with clinical and radiographic features consistent with short-limb skeletal dysplasia Al-Gazali type was collected. The affected individuals presented with moderate intrauterine growth restriction, relative macrocephaly, hypertrichosis, large anterior fontanelle, short neck, short and stiff limbs with small hands and feet, severe brachydactyly, and generalized bone sclerosis with mild platyspondyly. Biallelic disease-causing variants in ADAMTSL2 were detected using massively parallel sequencing (MPS) and Sanger sequencing techniques. Six individuals were compound heterozygous and one individual was homozygous for pathogenic variants in ADAMTSL2. In one of the families, pathogenic variants were detected in parental samples only. Overall, this study sheds light on the genetic cause of Al-Gazali skeletal dysplasia and identifies it as a semi-lethal part of the spectrum of ADAMTSL2-related disorders. Furthermore, we highlight the importance of meticulous analysis of the pseudogene region of ADAMTSL2 where disease-causing variants might be located.
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| 14. |
- Benetou, Vassiliki, et al.
(author)
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Fruit and Vegetable Intake and Hip Fracture Incidence in Older Men and Women : The CHANCES Project
- 2016
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In: Journal of Bone and Mineral Research. - : Wiley. - 0884-0431 .- 1523-4681. ; 31:9, s. 1743-1752
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Journal article (peer-reviewed)abstract
- The role of fruit and vegetable intake in relation to fracture prevention during adulthood and beyond is not adequately understood. We investigated the potential association between fruit and vegetable intake and hip fracture incidence in a large sample of elderly from Europe and United States. A total of 142,018 individuals (among which 116,509 women), aged ≥60 years old, from five cohorts, were followed-up prospectively for 1,911,482 person-years accumulating 5,552 hip fractures. Fruit and vegetable intake was assessed by validated, cohort-specific, food-frequency questionnaires. Ηip fractures were ascertained through national patient registers or telephone interviews/questionnaires. Adjusted hazard ratios (HR) derived by Cox proportional-hazards regression were estimated for each cohort and subsequently pooled using random-effects meta-analysis. Intake of ≤ 1 servings/day of fruit and vegetables combined was associated with 39% higher hip fracture risk [pooled adjusted HR:1.39, 95% Confidence Intervals (CIs): 1.20, 1.58] in comparison to moderate intake (>3 and ≤5 servings/day) (pfor heterogeneity = 0.505), whereas higher intakes (>5 servings/day) were not associated with lower risk in comparison to the same reference. Associations were more evident among women. We concluded that a daily intake of one or less servings of fruits and vegetables was associated with increased hip fracture risk in relation to moderate daily intakes. Older adults with such low fruit and vegetable consumption may benefit from raising their intakes to moderate amounts in order to reduce their hip fracture risk.
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| 15. |
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| 16. |
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| 17. |
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| 18. |
- Boonen, Steven, et al.
(author)
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Balloon Kyphoplasty for the Treatment of Acute Vertebral Compression Fractures: 2-Year Results From a Randomized Trial
- 2011
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In: Journal of Bone and Mineral Research. - : Wiley. - 1523-4681 .- 0884-0431. ; 26:7, s. 1627-1637
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Journal article (peer-reviewed)abstract
- 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). Quality of life, function, disability, and pain were assessed over 24 months. Kyphoplasty was associated with greater improvements in Short-Form 36 (SF-36) Physical Component Summary (PCS) scores when averaged across the 24-month follow-up period compared with nonsurgical therapy [overall treatment effect 3.24 points, 95% confidence interval (CI) 1.47-5.01, p = .0004]; the treatment difference remained statistically significant at 6 months (3.39 points, 95% CI 1.13-5.64, p = .003) but not at 12 months (1.70 points, 95% CI -0.59 to 3.98, p = .15) or 24 months (1.68 points, 95% CI -0.63 to 3.99, p = .15). Greater improvement in back pain was observed over 24 months for kyphoplasty (overall treatment effect -1.49 points, 95% CI -1.88 to -1.10, p<.0001); the difference between groups remained statistically significant at 24 months (-0.80 points, 95% CI -1.39 to -0.20, p = .009). There were two device-related serious adverse events in the second year that occurred at index vertebrae (a spondylitis and an anterior cement migration). There was no statistically significant difference between groups in the number of patients (47.5% for kyphoplasty, 44.1% for control) with new radiographic vertebral fractures; fewer fractures occurred (similar to 18%) within the second year. 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. (C) 2011 American Society for Bone and Mineral Research.
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| 19. |
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| 20. |
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| 21. |
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| 22. |
- Buttazzoni, Christian, et al.
(author)
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Does a childhood fracture predict low bone mass in young adulthood? - A 27-year prospective controlled study.
- 2013
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In: Journal of Bone and Mineral Research. - : Wiley. - 1523-4681 .- 0884-0431. ; 28:2, s. 351-359
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Journal article (peer-reviewed)abstract
- BACKGROUND: A fracture in childhood is associated with low bone mineral density (BMD), but it is debated whether a fracture at growth also predicts low BMD in young adulthood. PURPOSE: To gender-specifically evaluate whether children with a fracture are at increased risk of low BMD in young adulthood. METHODS: Distal forearm BMD (g/cm(2) ) was measured with single photon absorptiometry (SPA) in 47 boys and 26 girls (mean age 10 years, range 3-16) with an index fracture and in 41 boys and 43 girls (mean age 10 years, range 4-16) with no fracture. BMD was re-measured mean 27 years later with the same SPA apparatus and with dual energy absorptiometry (DXA), quantitative ultrasound (QUS) and peripheral computed tomography (pQCT). Individual Z-scores were calculated using the control cohort as reference population. Data are presented as means with 95% confidence intervals (95% CI) within brackets and correlation with Pearson's correlation coefficient RESULTS: Boys with an index fracture had at fracture event a distal forearm BMD Z-score of -0.4 (-0.7, -0.1) and at follow-up -0.4 (-0.7, -0.1). Corresponding values in girls were -0.2 (-0.5, 0.1) and -0.3 (-0.7, 0.1). The deficit in absolute bone mass was driven by men with index fractures in childhood due to low rather than moderate or high energy. There were no changes in BMD Z-score during the follow-up period. The BMD deficit at follow-up was in boys with an index fracture verified with all advocated techniques CONCLUSIONS: A childhood fracture in men was associated with low BMD and smaller bone size in young adulthood while the deficit in women did not reach statistical significance. © 2012 American Society for Bone and Mineral Research.
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| 23. |
- Byberg, Liisa, et al.
(author)
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Birth Weight is not Associated with Risk of Fracture : Results From Two Swedish Cohort Studies
- 2014
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In: Journal of Bone and Mineral Research. - : Wiley. - 0884-0431 .- 1523-4681. ; 29:10, s. 2152-2160
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Journal article (peer-reviewed)abstract
- Development and growth in utero has been suggested to influence bone health. However, the relationship with risk of fracture in old age is largely unknown. Using Cox proportional hazards regression, we studied the association between birth weight and fractures at ages 50-94 among 10,893 men and women (48% women) from the Uppsala Birth Cohort Study (UBCoS, born 1915-29) and 1,334 men from the Uppsala Longitudinal Study of Adult Men (ULSAM, born 1920-24). Measured birth weight was collected from hospital or midwives' records and fractures from the Swedish National Patient Register. We observed 2,796 fractures (717 of these were hip fractures) in UBCoS and 335 fractures (102 hip fractures) in ULSAM. In UBCoS, the hazard ratio (HR) per 1 kg increase in birth weight, adjusted for sex and socioeconomic status at birth, was 1.01 (95% confidence interval [CI], 0.94-1.09) for any fracture and 1.06 (95% CI, 0.91-1.23) for hip fracture. Estimates in ULSAM were similar. We did not observe a differential association of birth weight with fractures occurring before age 70 or after age 70 years. Neither birth weight standardized for gestational age nor gestational duration was associated with fracture rate. In linear regression, birth weight was not associated with bone mineral density among 303 82-year-old men in ULSAM but showed positive associations with total body bone mineral content (β per kg increase in birth weight, adjusted for social class and age, 133; 95% CI, 30-227). This association was attenuated after further adjustment for body mass index and height (β, 41; 95% CI, -43 to 126). We conclude that birth weight is associated with bone mineral content but this association does not translate into an association with risk of fracture in men and women aged 50-94 years.
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| 24. |
- Byberg, Liisa, et al.
(author)
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Fruit and vegetable intake and risk of hip fracture : A cohort study of Swedish men and women
- 2015
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In: Journal of Bone and Mineral Research. - : Wiley. - 0884-0431 .- 1523-4681. ; 30:6, s. 976-984
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Journal article (peer-reviewed)abstract
- Dietary guidelines recommend a daily intake of five servings of fruit and vegetables. Whether such intakes are associated with a lower risk of hip fracture is at present unclear. The aim of the present study was to investigate the dose-response association between habitual fruit and vegetable intake and hip fracture in a cohort study based on 40,644 men from the Cohort of Swedish Men (COSM) and 34,947 women from the Swedish Mammography Cohort (SMC) (total n=75,591), free from cardiovascular disease and cancer, who answered lifestyle questionnaires in 1997 (age 45-83 years). Intake of fruit and vegetables (servings/day) was assessed by food frequency questionnaire and incident hip fractures were retrieved from the Swedish Patient Register (1998-2010). The mean follow-up time was 14.2 years. One third of the participants reported an intake of fruit and vegetables of >5 servings/day, one third >3 to ≤5 servings/day, 28% >1 to ≤3 servings/day, and 6% reported ≤1 serving/day. During 1,037,645 person-years we observed 3,644 hip fractures (2,266, 62%, in women). The doseresponse association was found to be strongly non-linear (P<0.001). Men and women with zero consumption had 88% higher rate of hip fracture compared with those consuming 5 servings/day; adjusted hazard ratio (HR), 1.88 (95% CI, 1.53-2.32). The rate was gradually lower with higher intakes; adjusted HR for 1 vs 5 servings/day, 1.35 (95% CI, 1.21-1.58). However, more than 5 servings/day did not confer additionally lower HRs (adjusted HR for 8 vs. 5 servings/day, 0.96 (95% CI, 0.90-1.03). Similar results were observed when men and women were analyzed separately. We conclude that there is a dose-response association between fruit and vegetable intake and hip fracture such that an intake below the recommended 5 servings/day confers higher rates of hip fracture. Intakes above this recommendation do not seem to further lower the risk.
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| 25. |
- Byberg, Liisa, et al.
(author)
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Mediterranean Diet and Hip Fracture in Swedish Men and Women.
- 2016
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In: Journal of Bone and Mineral Research. - : Wiley. - 0884-0431 .- 1523-4681. ; 31:12, s. 2098-2105
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Journal article (peer-reviewed)abstract
- A Mediterranean diet, known to have beneficial effects on cardiovascular health, may also influence the risk of hip fracture although previous studies present discrepant results. We therefore aimed to determine whether the rate of hip fracture was associated with degree of adherence to a Mediterranean diet. We combined two Swedish cohort studies consisting of 37,903 men and 33,403 women (total n = 71,333, mean age 60 years) free of previous cardiovascular disease and cancer who answered a medical and a food-frequency questionnaire in 1997. A modified Mediterranean diet score (mMED; range, 0 to 8 points) was created based on high consumption of fruits and vegetables, legumes and nuts, whole grains, fermented dairy products, fish, and olive/rapeseed oil, moderate intake of alcohol, and low intake of red and processed meat. Incident hip fractures between January 1, 1998, and December 31, 2012, were retrieved from the National Patient Register. Hazard ratios (HRs) and 95% confidence intervals (CIs) adjusted for potential confounders were calculated using Cox proportional hazards regression. Differences in age at hip fracture were calculated using multivariable Laplace regression. During follow-up, 3175 hip fractures occurred at a median age of 73.3 years. One unit increase in the mMED was associated with 6% lower hip fracture rate (adjusted HR = 0.94; 95% CI, 0.92 to 0.96) and with a 3-month higher median age at hip fracture (50th percentile difference = 2.8 months; 95% CI, 1.4 to 4.2). Comparing the highest quintile of adherence to the mMED (6 to 8 points) with the lowest (0 to 2 points) conferred an adjusted HR of hip fracture of 0.78 (95% CI, 0.69 to 0.89) and a 12-month higher median age of hip fracture (50th percentile difference = 11.6 months; 95% CI, 4.2 to 19.0). Results were similar in men and women. We conclude that higher adherence to a Mediterranean-like diet is associated with lower risk of future hip fracture.
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| 26. |
- Byberg, Liisa, et al.
(author)
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Prediction of fracture risk in men : A cohort study
- 2012
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In: Journal of Bone and Mineral Research. - : Wiley. - 0884-0431 .- 1523-4681. ; 27:4, s. 797-807
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Journal article (peer-reviewed)abstract
- FRAX is a tool that identifies individuals with high fracture risk who will benefit from pharmacological treatment of osteoporosis. However, a majority of fractures among elderly occur in people without osteoporosis and most occur after a fall. Our aim was to accurately identify men with a high future risk of fracture, independent of cause. In the population-based Uppsala Longitudinal Study of Adult Men (ULSAM) and using survival analysis we studied different models' prognostic values (R(2) ) for any fracture and hip fracture within 10 years from age 50 (n = 2322), 60 (n = 1852), 71 (n = 1221), and 82 (n = 526). During the total follow-up period from age 50, 897 fractures occurred in 585 individuals. Of these, 281 were hip fractures occurring in 189 individuals. The rates of any fracture were 5.7/1000 person-years at risk from age 50 and 25.9/1000 person-years at risk from age 82. Corresponding hip fractures rates were 2.9 and 11.7/1000 person-years at risk. The FRAX model included all variables in FRAX except bone mineral density. The full model combining FRAX variables, comorbidity, medications, and behavioral factors explained 25-45% of all fractures and 80-92% of hip fractures, depending on age. The corresponding prognostic values of the FRAX model were 7-17% for all fractures and 41-60% for hip fractures. Net reclassification improvement (NRI) comparing the full model with the FRAX model ranged between 40 and 53% for any fracture and between 40 and 87% for hip fracture. Within the highest quintile of predicted fracture risk with the full model, 1/3 of the men will have a fracture within 10 years after age 71 years and 2/3 after age 82 years. We conclude that the addition of comorbidity, medication and behavioral factors to the clinical components of FRAX can substantially improve the ability to identify men at high risk of fracture, especially hip fracture.
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| 27. |
- Börjesson, Anna E, et al.
(author)
-
The role of activation functions 1 and 2 of estrogen receptor-alpha for the effects of estradiol and selective estrogen receptor modulators in male mice
- 2013
-
In: Journal of Bone and Mineral Research. - : Wiley. - 0884-0431 .- 1523-4681. ; 28:5, s. 1117-1126
-
Journal article (peer-reviewed)abstract
- Estradiol (E2) is important for male skeletal health and the effect of E2 is mediated via estrogen receptor (ER)-. This was demonstrated by the findings that men with an inactivating mutation in aromatase or a nonfunctional ER had osteopenia and continued longitudinal growth after sexual maturation. The aim of the present study was to evaluate the role of different domains of ER for the effects of E2 and selective estrogen receptor modulators (SERMs) on bone mass in males. Three mouse models lacking either ERAF-1 (ERAF-10), ERAF-2 (ERAF-20), or the total ER (ER/) were orchidectomized (orx) and treated with E2 or placebo. E2 treatment increased the trabecular and cortical bone mass and bone strength, whereas it reduced the thymus weight and bone marrow cellularity in orx wild type (WT) mice. These parameters did not respond to E2 treatment in orx ER/ or ERAF-20 mirx ERAF-10 mice were tissue-dependent, with a clear response in cortical bone parameters and bone marrow cellularity, but no response in trabecular bone. To determine the role of ERAF-1 for the effects of SERMs, we treated orx WT and ERAF-10 mice with raloxifene (Ral), lasofoxifene (Las), bazedoxifene (Bza), or vehicle. These SERMs increased total body areal bone mineral density (BMD) and trabecular volumetric BMD to a similar extent in orx WT mice. Furthermore, only Las increased cortical thickness significantly and only Bza increased bone strength significantly. However, all SERMs showed a tendency toward increased cortical bone parameters. Importantly, all SERM effects were absent in the orx ERAF-10 mice. In conclusion, ERAF-2 is required for the estrogenic effects on all evaluated parameters, whereas the role of ERAF-1 is tissue-specific. All evaluated effects of Ral, Las and Bza are dependent on a functional ERAF-1. Our findings might contribute to the development of bone-specific SERMs in males. (c) 2013 American Society for Bone and Mineral Research.
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| 28. |
- Börjesson, Anna E, et al.
(author)
-
The role of estrogen receptor-alpha in growth plate cartilage for longitudinal bone growth.
- 2010
-
In: Journal of bone and mineral research. - : Wiley. - 1523-4681 .- 0884-0431. ; 25:12, s. 2414-24
-
Journal article (peer-reviewed)abstract
- Estrogens enhance skeletal growth during early sexual maturation while high estradiol levels during late puberty result in growth plate fusion in humans. Although the growth plates do not fuse directly after sexual maturation in rodents, a reduction in growth plate height is seen by treatment with a high dose of estradiol. It is unknown whether the effects of estrogens on skeletal growth are mediated directly via estrogen receptors (ERs) in growth plate cartilage and/or indirectly via other mechanisms such as the GH/IGF-I axis. To determine the role of ERalpha in growth plate cartilage for skeletal growth, we developed a mouse model with cartilage-specific inactivation of ERalpha. Although mice with total ERalpha inactivation displayed affected longitudinal bone growth associated with alterations in the GH/IGF-I axis, the skeletal growth was normal during sexual maturation in mice with cartilage-specific ERalpha inactivation. High dose estradiol treatment of adult mice reduced the growth plate height as a consequence of attenuated proliferation of growth plate chondrocytes in control mice but not in cartilage-specific ERalpha(-/-) mice. Adult cartilage-specific ERalpha(-/-) mice continued to grow after four months of age while growth was limited in control mice, resulting in increased femur length in one-year-old cartilage-specific ERalpha(-/-) mice compared with control mice. We conclude that during early sexual maturation ERalpha in growth plate cartilage is not important for skeletal growth. In contrast, it is essential for high dose estradiol to reduce the growth plate height in adult mice and for reduction of longitudinal bone growth in elderly mice. (c) 2010 American Society for Bone and Mineral Research.
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| 29. |
- Capulli, Mattia, et al.
(author)
-
The C-Terminal Domain of Chondroadherin: A New Regulator of Osteoclast Motility Counteracting Bone Loss
- 2014
-
In: Journal of Bone and Mineral Research. - : Wiley. - 1523-4681 .- 0884-0431. ; 29:8, s. 1833-1846
-
Journal article (peer-reviewed)abstract
- Chondroadherin (CHAD) is a leucine-rich protein promoting cell attachment through binding to integrin alpha(2)beta(1) and syndecans. We observed that CHAD mRNA and protein were lower in bone biopsies of 50-year-old to 65-year-old osteoporotic women and in bone samples of ovariectomized mice versus gender/age-matched controls, suggesting a role in bone metabolism. By the means of an internal cyclic peptide (cyclicCHAD), we observed that its integrin binding sequence impaired preosteoclast migration through a nitric oxide synthase 2-dependent mechanism, decreasing osteoclastogenesis and bone resorption in a concentration-dependent fashion, whereas it had no effect on osteoblasts. Consistently, cyclicCHAD reduced transcription of two nitric oxide downstream genes, migfilin and vasp, involved in cell motility. Furthermore, the nitric oxide donor, S-nitroso-N-acetyl-D, L-penicillamine, stimulated preosteoclast migration and prevented the inhibitory effect of cyclicCHAD. Conversely, the nitric oxide synthase 2 (NOS2) inhibitor, N5-(1-iminoethyl)-l-ornithine, decreased both preosteoclast migration and differentiation, confirming a role of the nitric oxide pathway in the mechanism of action triggered by cyclicCHAD. In vivo, administration of cyclicCHAD was well tolerated and increased bone volume in healthy mice, with no adverse effect. In ovariectomized mice cyclicCHAD improved bone mass by both a preventive and a curative treatment protocol, with an effect in line with that of the bisphosphonate alendronate, that was mimicked by the NOS2 inhibitor [L-N6-(1-Iminoethyl)-lysine. 2 dihydrochloride]. In both mouse models, cyclicCHAD reduced osteoclast and bone resorption without affecting osteoblast parameters and bone formation. In conclusion, CHAD is a novel regulator of bone metabolism that, through its integrin binding domain, inhibits preosteoclast motility and bone resorption, with a potential translational impact for the treatment of osteoporosis. (C) 2014 American Society for Bone and Mineral Research.
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| 30. |
- Chen, Jie, et al.
(author)
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Association of Sleep Traits and Heel Bone Mineral Density : Observational and Mendelian Randomization Studies
- 2021
-
In: Journal of Bone and Mineral Research. - : John Wiley & Sons. - 0884-0431 .- 1523-4681. ; 36:11, s. 2184-2192
-
Journal article (peer-reviewed)abstract
- Observational studies have suggested that sleep and circadian disturbances are potentially modifiable risk factors for low bone mineral density (BMD), but the causal relationship is unclear. This study aimed to (i) replicate the findings by examining observational association of sleep traits with low estimated BMD); (ii) examine whether these associations were causal by using Mendelian randomization (MR) analyses; and (iii) investigate potential modulation effects of sex and menopause. A total of 398,137 White British subjects (aged 39 to 73 years) with valid BMD estimated by quantitative ultrasound of the heel (eBMD) at baseline were included. Linear regression analyses and inverse-variance weighted method were used as main methods for observational and one-sample MR analyses, respectively, to investigate the associations between self-reported sleep traits (sleep duration, chronotype, daytime sleepiness, and insomnia) and low eBMD. Furthermore, sensitivity analyses were performed in subgroups based on sex and menopause in both observational and MR analyses. In observational analyses, short/long sleep, insomnia, and definite eveningness were associated with low eBMD (short sleep: beta = -0.045, effect in standard deviation change of rank-based inverse normally transformed eBMD; long sleep: beta = -0.028; sometimes insomnia: beta = -0.012; usually insomnia: beta = -0.021; definite eveningness: beta = -0.047), whereas definite morningness was associated with decreased risk of low eBMD (beta = 0.011). Subgroup analyses suggested associations of short/long sleep and definite eveningness with low eBMD among men, short sleep with low eBMD among premenopausal women, and short sleep, eveningness, and daytime sleepiness among postmenopausal women. In bidirectional MR analyses, there was no causal relationship between sleep traits and eBMD in either overall sample or subgroup analyses. In summary, although observational analysis showed a robust association of low eBMD with sleep duration, chronotype, and insomnia, there was no evidence of causal relationship as suggested by MR analysis.
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| 31. |
- Conley, R. B., et al.
(author)
-
Secondary Fracture Prevention: Consensus Clinical Recommendations from a Multistakeholder Coalition
- 2020
-
In: Journal of Bone and Mineral Research. - : Wiley. - 0884-0431 .- 1523-4681. ; 35:1, s. 36-52
-
Journal article (peer-reviewed)abstract
- Osteoporosis-related fractures are undertreated, due in part to misinformation about recommended approaches to patient care and discrepancies among treatment guidelines. To help bridge this gap and improve patient outcomes, the American Society for Bone and Mineral Research assembled a multistakeholder coalition to develop clinical recommendations for the optimal prevention of secondary fracture among people aged 65 years and older with a hip or vertebral fracture. The coalition developed 13 recommendations (7 primary and 6 secondary) strongly supported by the empirical literature. The coalition recommends increased communication with patients regarding fracture risk, mortality and morbidity outcomes, and fracture risk reduction. Risk assessment (including fall history) should occur at regular intervals with referral to physical and/or occupational therapy as appropriate. Oral, intravenous, and subcutaneous pharmacotherapies are efficacious and can reduce risk of future fracture. Patients need education, however, about the benefits and risks of both treatment and not receiving treatment. Oral bisphosphonates alendronate and risedronate are first-line options and are generally well tolerated; otherwise, intravenous zoledronic acid and subcutaneous denosumab can be considered. Anabolic agents are expensive but may be beneficial for selected patients at high risk. Optimal duration of pharmacotherapy is unknown but because the risk for second fractures is highest in the early post-fracture period, prompt treatment is recommended. Adequate dietary or supplemental vitamin D and calcium intake should be assured. Individuals being treated for osteoporosis should be reevaluated for fracture risk routinely, including via patient education about osteoporosis and fractures and monitoring for adverse treatment effects. Patients should be strongly encouraged to avoid tobacco, consume alcohol in moderation at most, and engage in regular exercise and fall prevention strategies. Finally, referral to endocrinologists or other osteoporosis specialists may be warranted for individuals who experience repeated fracture or bone loss and those with complicating comorbidities (eg, hyperparathyroidism, chronic kidney disease). (c) 2019 American Society for Bone and Mineral Research.
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| 32. |
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| 33. |
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| 34. |
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| 35. |
- Darelid, Anna, et al.
(author)
-
Catch up in bone acquisition in young adult men with late normal puberty.
- 2012
-
In: Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. - : Wiley. - 1523-4681. ; 27:10, s. 2198-2207
-
Journal article (peer-reviewed)abstract
- The aim of this study was to investigate the development of bone mineral density (BMD) and content (BMC) in relation to peak height velocity (PHV), and to investigate whether late normal puberty was associated with remaining low BMD and BMC in early adulthood in men. In total, 501 men (18.9±0.5 (mean±SD) yrs at baseline) were included in this five-year longitudinal study. Areal BMD (aBMD) and BMC, volumetric BMD (vBMD) and cortical bone size were measured using DXA and pQCT. Detailed growth and weight charts were used to calculate age at PHV, an objective assessment of pubertal timing. Age at PHV was a strong positive predictor of the increase in aBMD and BMC of the total body (R(2) aBMD 11.7%;BMC 4.3%), radius (R(2) aBMD 23.5%;BMC 22.3%), and lumbar spine (R(2) aBMD 11.9%;BMC 10.5%) between 19 and 24 yrs (p<0.001). Subjects were divided into three groups according to age at PHV (early, middle and late). Men with late puberty gained markedly more in aBMD and BMC at the total body, radius and lumbar spine, and lost less at the femoral neck (p<0.001) than men with early puberty. At age 24, no significant differences in aBMD or BMC of the lumbar spine, femoral neck, or total body were observed, while a deficit of 4.2% in radius aBMD, but not in BMC, was seen for men with late vs. early puberty (p<0.001). PQCT measurements of the radius at follow-up demonstrated no significant differences in bone size, whereas cortical and trabecular vBMD were 0.7% (p<0.001) and 4.8% (p<0.05) lower in men with late vs. early puberty. In conclusion, our results demonstrate that late puberty in males was associated with a substantial catch up in aBMD and BMC in young adulthood, leaving no deficits of the lumbar spine, femoral neck or total body at age 24.
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| 36. |
- Darelid, Anna, et al.
(author)
-
Trabecular Volumetric Bone Mineral Density is Associated With Previous Fracture During Childhood and Adolescence in Males - The GOOD Study.
- 2010
-
In: Journal of bone and mineral research. - : Wiley. - 1523-4681 .- 0884-0431. ; 25:3, s. 537-44
-
Journal article (peer-reviewed)abstract
- Abstract Areal bone mineral density (aBMD) measured with dual X-ray absorptiometry (DXA) has been associated with fracture risk in children and adolescents, but it remains unclear whether this association is due to volumetric BMD (vBMD) of the cortical and/or trabecular bone compartments or the bone size. The aim of this study was to determine whether vBMD or bone size was associated with x-ray verified fractures in men during growth. In total, 1068 men (age 18.9+/-0.6 yrs), were included in the population-based Gothenburg Osteoporosis and Obesity Determinants (GOOD) study. Areal BMD was measured by DXA, while cortical and trabecular vBMD and bone size were measured by peripheral quantitative computerized tomography (pQCT). X-ray records were searched for fractures. Self reported fractures in 77 men could not be confirmed in these records. These men were excluded, resulting in 991 included men, of which 304 men had an x-ray verified fracture and 687 were non-fracture subjects. Growth charts were used to establish the age of peak height velocity (PHV, n=600). Men with prevalent fractures had lower aBMD (lumbar spine 2.3%, p=0.005; total femur 2.6%, p=0.004, radius 2.1%, p<0.001) at all measured sites than men without fracture. Using pQCT measurements, we found that men with a prevalent fracture had markedly lower trabecular vBMD (radius: 6.6 %, p=7.5x10(-8); tibia: 4.5 %, p=1.7x10(-7)) as well as slightly lower cortical vBMD (radius: 0.4 %, p=0.0012; tibia: 0.3 %, p=0.015), but not reduced cortical cross sectional area, than men without fracture. Every SD decrease in trabecular vBMD of the radius and tibia was associated with 1.46 (radius CI 1.26-1.69 (95% CI); tibia CI 1.26-1.68) times increased fracture prevalence. The peak fracture incidence coincided with the timing of PHV (+/-1 year). In conclusion, trabecular vBMD, but not aBMD, was independently associated with prevalent x-ray verified fractures in young men. Further studies are needed to determine if assessment of trabecular vBMD could enhance prediction of fractures during growth in males.
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| 37. |
- Detter, Fredrik, et al.
(author)
-
A Six-Year Exercise Program Improves Skeletal Traits without Affecting Fracture Risk - a Prospective Controlled Study in 2621 Children
- 2014
-
In: Journal of bone and mineral research. - : Wiley. - 0884-0431 .- 1523-4681. ; 29:6, s. 1325-1336
-
Journal article (peer-reviewed)abstract
- Most pediatric exercise intervention studies, that evaluates the effect on skeletal traits include volunteers and follow bone mass for less than three years. We present a population-based six-year controlled exercise intervention study in children with also bone structure and incident fractures as endpoints. Fractures were registered in 417 girls and 500 boys in the intervention group (3969 person-years) and 835 girls and 869 boys in the control group (8245 person-years), all aged 6-9 years at study start, during the six-year study period. Children in the intervention group had 40 minutes daily school physical education (PE) and the control group 60 minutes per week. In a sub-cohort with 78 girls and 111 boys in the intervention group and 52 girls and 54 boys in the control group, bone mineral density (g/cm2 ) and bone area (mm2 ) were measured repeatedly by dual energy X-ray absorptiometry (DXA). Peripheral quantitative computed tomography (pQCT) measured bone mass and bone structure at follow-up. There were 21.7 low and moderate energy related fractures per 1000 person-years in the intervention group and 19.8 fractures in the control group, leading to a Rate Ratio (RR) of 1.12 (0.85, 1.46). Girls in the intervention group, in comparison with girls in the control group, had 0.009 g/cm2 (0.003, 0.015) larger gain annually in spine BMD, 0.07 g (0.014, 0.123) larger gain in femoral neck BMC and 4.0 mm2 (0.5, 7.8) larger gain in femoral neck area, and at follow-up 24.1 g (7.6, 40.6) higher tibial cortical BMC (g) and 23.9 mm2 (5.27, 42.6) larger tibial cross-sectional area. Boys with daily PE had 0.006 g/cm2 (0.002, 0.010) larger gain annually in spine BMD than control boys but at follow-up no higher pQCT values than boys in the control group. Daily PE for six years in at study start 6-9 year old improves bone mass and bone size in girls and bone mass in boys, without affecting the fracture risk. (c) 2014 American Society for Bone and Mineral Research.
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| 38. |
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| 39. |
- Ebeling, Peter R., et al.
(author)
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The Efficacy and Safety of Vertebral Augmentation : A Second ASBMR Task Force Report
- 2019
-
In: Journal of Bone and Mineral Research. - : Wiley. - 0884-0431 .- 1523-4681. ; 34:1, s. 3-21
-
Journal article (peer-reviewed)abstract
- Vertebral augmentation is among the current standards of care to reduce pain in patients with vertebral fractures (VF), yet a lack of consensus regarding efficacy and safety of percutaneous vertebroplasty and kyphoplasty raises questions on what basis clinicians should choose one therapy over another. Given the lack of consensus in the field, the American Society for Bone and Mineral Research (ASBMR) leadership charged this Task Force to address key questions on the efficacy and safety of vertebral augmentation and other nonpharmacological approaches for the treatment of pain after VF. This report details the findings and recommendations of this Task Force. For patients with acutely painful VF, percutaneous vertebroplasty provides no demonstrable clinically significant benefit over placebo. Results did not differ according to duration of pain. There is also insufficient evidence to support kyphoplasty over nonsurgical management, percutaneous vertebroplasty, vertebral body stenting, or KIVA®. There is limited evidence to determine the risk of incident VF or serious adverse effects (AE) related to either percutaneous vertebroplasty or kyphoplasty. No recommendation can be made about harms, but they cannot be excluded. For patients with painful VF, it is unclear whether spinal bracing improves physical function, disability, or quality of life. Exercise may improve mobility and may reduce pain and fear of falling but does not reduce falls or fractures in individuals with VF. General and intervention-specific research recommendations stress the need to reduce study bias and address methodological flaws in study design and data collection. This includes the need for larger sample sizes, inclusion of a placebo control, more data on serious AE, and more research on nonpharmacologic interventions. Routine use of vertebral augmentation is not supported by current evidence. When it is offered, patients should be fully informed about the evidence. Anti-osteoporotic medications reduce the risk of subsequent vertebral fractures by 40–70%.
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| 40. |
- Engström, Annette, et al.
(author)
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Long-term cadmium exposure and the association with bone mineral density and fractures in a population-based study among women
- 2011
-
In: Journal of Bone and Mineral Research. - : Wiley. - 0884-0431 .- 1523-4681. ; 26:3, s. 486-495
-
Journal article (peer-reviewed)abstract
- BACKGROUND:: All people are exposed to cadmium (Cd) via food, smokers are additionally exposed. High Cd exposure is associated with severe bone damage, but the public health impact in relation to osteoporosis and fractures at low environmental exposure remains to be clarified. METHODS:: Within the population-based Swedish Mammography Cohort, we assessed urinary Cd (U-Cd, mug/g creatinine, cr) as a marker of life-time exposure and bone mineral density (BMD) by DXA among 2,688 women. Register-based information on fractures was retrieved from 1997 to 2009. Associations were evaluated by multivariable regression analyses. RESULTS:: In linear regression U-Cd was inversely associated with BMD at the total body (p<0.001), femoral neck (p=0.025), total hip (p=0.004), lumbar spine (p=0.088), and volumetric femoral neck (p=0.013). In comparison to women with U-Cd <0.50 mug/g cr, those with U-Cd >/=0.75 mug/g cr had OR 2.45 (95% CI, 1.51-3.97) and 1.97 (95% CI, 1.24-3.14) for osteoporosis at the femoral neck and lumbar spine, respectively. Among never-smokers, the corresponding ORs were 3.45 (95% CI, 1.46-8.23) and 3.26 (95% CI, 1.44-7.38). For any first fracture (n=395) OR was 1.16 (95% CI, 0.89-1.50) comparing U-Cd >/=0.5 mug/g cr with lower levels. Among never-smokers, the ORs (95% CIs) were 2.03 (1.33-3.09) for any first fracture, 2.06 (1.28-3.32) for first osteoporotic fracture, 2.18 (1.20-3.94) for first distal forearm fracture and 1.89 (1.25-2.85) for multiple incident fractures. CONCLUSIONS:: U-Cd at low environmental exposure from food in a general population of women showed modest but significant association with both BMD and fractures especially in never smokers indicating a larger concern than previously known.
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| 41. |
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| 42. |
- Eriksson, Anna-Lena, 1971, et al.
(author)
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High-Sensitivity CRP Is an Independent Risk Factor for All Fractures and Vertebral Fractures in Elderly Men : The MrOS Sweden Study
- 2014
-
In: Journal of Bone and Mineral Research. - : Wiley. - 0884-0431 .- 1523-4681. ; 29:2, s. 418-423
-
Journal article (peer-reviewed)abstract
- Epidemiological studies have shown low-grade inflammation measured by high-sensitivity C-reactive protein (hs-CRP) to be associated with fracture risk in women. However, it is still unclear whether hs-CRP is also associated with fracture risk in men. We therefore measured serum levels of hs-CRP in 2910 men, mean age 75 years, included in the prospective population-based MrOS Sweden cohort. Study participants were divided into tertile groups based on hs-CRP level. Fractures occurring after the baseline visit were validated (average follow-up 5.4 years). The incidence for having at least one fracture after baseline was 23.9 per 1000 person-years. In Cox proportional hazard regression analyses adjusted for age, hs-CRP was related to fracture risk. The hazard ratio (HR) of fracture for the highest tertile of hs-CRP, compared with the lowest and the medium tertiles combined, was 1.48 (95% CI, 1.20-1.82). Multivariate adjustment for other risk factors for fractures had no major effect on the associations between hs-CRP and fracture. Results were essentially unchanged after exclusion of subjects with hs-CRP levels greater than 7.5mg/L, as well as after exclusion of subjects with a first fracture within 3 years of follow-up, supporting that the associations between hs-CRP and fracture risk were not merely a reflection of a poor health status at the time of serum sampling. Femoral neck bone mineral density (BMD) was not associated with hs-CRP, and the predictive role of hs-CRP for fracture risk was essentially unchanged when femoral neck BMD was added to the model (HR, 1.37; 95% CI, 1.09-1.72). Exploratory subanalyses of fracture type demonstrated that hs-CRP was clearly associated with clinical vertebral fractures (HR, 1.61; 95% CI, 1.12-2.29). We demonstrate, using a large prospective population-based study, that elderly men with high hs-CRP have increased risk of fractures, and that these fractures are mainly vertebral. The association between hs-CRP and fractures was independent of BMD. (c) 2014 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals, Inc. on behalf of the American Society for Bone and Mineral Research. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
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| 43. |
- Eriksson, Joel, et al.
(author)
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Limited Clinical Utility of a Genetic Risk Score for the Prediction of Fracture Risk in Elderly Subjects
- 2015
-
In: Journal of Bone and Mineral Research. - : Wiley. - 1523-4681 .- 0884-0431. ; 30:1, s. 184-194
-
Journal article (peer-reviewed)abstract
- It is important to identify the patients at highest risk of fractures. A recent large-scale meta-analysis identified 63 autosomal single-nucleotide polymorphisms (SNPs) associated with bone mineral density (BMD), of which 16 were also associated with fracture risk. Based on these findings, two genetic risk scores (GRS63 and GRS16) were developed. Our aim was to determine the clinical usefulness of these GRSs for the prediction of BMD, BMD change, and fracture risk in elderly subjects. We studied two male (Osteoporotic Fractures in Men Study [MrOS] US, MrOS Sweden) and one female (Study of Osteoporotic Fractures [SOF]) large prospective cohorts of older subjects, looking at BMD, BMD change, and radiographically and/or medically confirmed incident fractures (8067 subjects, 2185 incident nonvertebral or vertebral fractures). GRS63 was associated with BMD (3% of the variation explained) but not with BMD change. Both GRS63 and GRS16 were associated with fractures. After BMD adjustment, the effect sizes for these associations were substantially reduced. Similar results were found using an unweighted GRS63 and an unweighted GRS16 compared with those found using the corresponding weighted risk scores. Only minor improvements in C-statistics (AUC) for fractures were found when the GRSs were added to a base model (age, weight, and height), and no significant improvements in C-statistics were found when they were added to a model further adjusted for BMD. Net reclassification improvements with the addition of the GRSs to a base model were modest and substantially attenuated in BMD-adjusted models. GRS63 is associated with BMD, but not BMD change, suggesting that the genetic determinants of BMD differ from those of BMD change. When BMD is known, the clinical utility of the two GRSs for fracture prediction is limited in elderly subjects. (c) 2014 American Society for Bone and Mineral Research.
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| 44. |
- Finnilä, Mikko A J, et al.
(author)
-
Mineral Crystal Thickness in Calcified Cartilage and Subchondral Bone in Healthy and Osteoarthritic Human Knees
- 2022
-
In: Journal of Bone and Mineral Research. - : Wiley. - 1523-4681 .- 0884-0431. ; 37:9, s. 1700-1710
-
Journal article (peer-reviewed)abstract
- Osteoarthritis (OA) is the most common joint disease, where articular cartilage degradation is often accompanied with sclerosis of the subchondral bone. However, the association between OA and tissue mineralization at the nanostructural level is currently not understood. In particular, it is technically challenging to study calcified cartilage, where relevant but poorly understood pathological processes such as tidemark multiplication and advancement occur. Here, we used state-of-the-art microfocus small-angle X-ray scattering with a 5-μm spatial resolution to determine the size and organization of the mineral crystals at the nanostructural level in human subchondral bone and calcified cartilage. Specimens with a wide spectrum of OA severities were acquired from both medial and lateral compartments of medial compartment knee OA patients (n = 15) and cadaver knees (n = 10). Opposing the common notion, we found that calcified cartilage has thicker and more mutually aligned mineral crystals than adjoining bone. In addition, we, for the first time, identified a well-defined layer of calcified cartilage associated with pathological tidemark multiplication, containing 0.32 nm thicker crystals compared to the rest of calcified cartilage. Finally, we found 0.2 nm thicker mineral crystals in both tissues of the lateral compartment in OA compared with healthy knees, indicating a loading-related disease process because the lateral compartment is typically less loaded in medial compartment knee OA. In summary, we report novel changes in mineral crystal thickness during OA. Our data suggest that unloading in the knee might be involved with the growth of mineral crystals, which is especially evident in the calcified cartilage.
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| 45. |
- Flores Bjurström, Carmen, et al.
(author)
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Nonablative neonatal bone marrow transplantation rapidly reverses severe murine osteopetrosis despite low level engraftment and lack of selective expansion of the osteoclastic lineage.
- 2010
-
In: Journal of Bone and Mineral Research. - : Wiley. - 1523-4681 .- 0884-0431. ; 25:9, s. 2069-2077
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Journal article (peer-reviewed)abstract
- Infantile malignant osteopetrosis (IMO) is caused by lack of functional osteoclasts leading to skeletal abnormalities, blindness due to compression of the optic nerves, bone marrow (BM) failure and early death. In most patients TCIRG1, a proton pump subunit essential for bone resorption, is mutated. Oc/oc mice represent a model for IMO due to a deletion in Tcirg1 and die around 4 weeks. To determine if hematopoietic stem cell transplantation without prior conditioning can reverse osteopetrosis, neonatal mice were transplanted iv with lineage depleted BM cells. More than 85% of oc/oc mice transplanted with 5 x 10(6) cells survived long term with an engraftment of 3-5% in peripheral blood (PB). At 3 w engraftment in the BM was 1-2% but the cellularity had increased 60-fold compared to non-treated oc/oc and RANKL and M-CSF expression in the BM was normalized. Histopathology and micro-CT revealed almost complete reversal of osteopetrosis after 4 weeks. In vitro studies showed that bone resorption by osteoclasts from transplanted oc/oc mice was 14% of transplanted controls and immunofluorescence microscopy revealed that resorption was mainly associated with osteoclasts of donor origin. Lineage analysis of BM, PB and spleen did not provide any evidence for selective recruitment of cells to the osteoclastic lineage. The vision was also preserved in transplanted oc/oc mice as determined by a visual tracking drum test. In summary, nonablative neonatal transplantation leading to engraftment of only a small fraction of normal cells rapidly reverses severe osteopetrosis in the oc/oc mouse model. (c) 2010 American Society for Bone and Mineral Research.
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| 46. |
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| 47. |
- Freyschuss, B., et al.
(author)
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Real-World Effectiveness of Anti-Resorptive Treatment in Patients With Incident Fragility Fractures—The STORM Cohort—A Swedish Retrospective Observational Study
- 2022
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In: Journal of Bone and Mineral Research. - : Wiley. - 0884-0431 .- 1523-4681. ; 37:4, s. 649-659
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Journal article (peer-reviewed)abstract
- Results from real-world evidence (RWE) from the largest healthcare region in Sweden show low uptake of antiresorptive (AR) treatment, but beneficial effect in those receiving treatment, especially for the composite outcome of hip fracture or death. For RWE studies, Sweden is unique, with virtually complete coverage of electronic medical records (EMRs) and both regional and national registries, in a universal publicly funded healthcare system. To our knowledge, there is no previous RWE study evaluating the efficacy of AR treatment compared to no AR treatment after fragility fracture, including data on parenteral treatments administered in hospital settings. The Stockholm Real World Management (STORM) study cohort was established in the healthcare region of Stockholm to retrospectively assess the effectiveness of AR treatment after first fragility fracture using the regional EMR system for both hospital and primary care. Between 2012 and 2018, we identified 69,577 fragility fracture episodes among 59,078 patients, men and women, 50 years and older. Of those, 21,141 patients met inclusion and exclusion criteria (eligible cohort). From these, the final matched study cohort comprised 9840 fragility fractures (cases receiving AR treatment [n=1640] and controls not receiving AR treatment [n=8200]). Propensity scores were estimated using logistic regression models with AR treatment as outcome and confounders as independent variables followed by analysis using Cox proportional hazard models. Real world evidence from Sweden's largest healthcare region, comprising a quarter of the Swedish population, show that only 10% of patients receive AR treatment within 1 year after a fragility fracture. Factors associated with not receiving treatment include having a diagnosis of cardiovascular disease. In those treated, AR have positive effects particularly on the composite of fracture and death (any fracture/death and hip fracture/death) in individuals matched for all major confounders. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR). © 2022 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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| 48. |
- Gandham, Anoohya, et al.
(author)
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Sarcopenia definitions and their association with fracture risk in older Swedish women
- 2024
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In: JOURNAL OF BONE AND MINERAL RESEARCH. - 0884-0431 .- 1523-4681. ; 39:4, s. 453-461
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Journal article (peer-reviewed)abstract
- The purpose of this study was to investigate the prevalence of three sarcopenia definitions and their associations with fracture risk in older Swedish women when adjusted for fracture risk assessment (FRAX)-based risk factors; 2,883 women with a mean age of 77.8 years were included. Sarcopenia was defined based on the Sarcopenia Definitions and Outcomes Consortium (SDOC; low handgrip strength [kg] and gait speed (m/s)), revised European Working Group on Sarcopenia in Older People (EWGSOP2; low appendicular lean mass index, appendicular lean mass [ALM]/height; kg/m2], and hand grip strength [kg]), and Asian Working Group for Sarcopenia (AWGS; low ALM (kg), and hand grip strength [kg]) definitions. Femoral neck T-score was obtained from dual-energy X-ray absorptiometry. All fractures, confirmed by X-ray or medical record review, were subsequently categorized as major osteoporotic fractures (MOFs) and hip fractures. Deaths were verified through regional registers. The total follow-up time was 6.4 +/- 1.3 (mean +/- SD) yr. Cox regression (hazard ratios [HR] and 95% CIs) analyses were performed with adjustment for age, FRAX variables, and femoral neck T-score. Sarcopenia prevalence was 4.5% (n = 129) according to SDOC, 12.5% (n = 360) for EWGSOP2, and 10.3% (n = 296) defined by AWGS. Individuals with sarcopenia defined by SDOC had a higher mortality risk than individuals without sarcopenia (HR: 3.41; 95% CI: 2.51, 4.62) after adjusting for age and FRAX variables. Sarcopenia according to EWGSOP2 and AWGS was not associated with an increased fracture risk after adjusting for age and FRAX variables. Individuals with sarcopenia defined by SDOC had a higher risk for any fractures (HR: 1.48; 95% CI: 1.10, 1.99) and MOF (HR: 1.42; 95% CI: 1.03, 1.98) compared with individuals without sarcopenia after adjusting for clinical risk factors used in FRAX. In conclusion, sarcopenia defined by SDOC, incorporating muscle function/strength, was the only sarcopenia definition associated with fracture risk in older women. This study aimed to investigate the risk of sarcopenia on fracture risk in older Swedish women. Data were utilized from 2,883 women aged 75-80 yr in the Swedish Sahlgrenska University Hospital Prospective Evaluation of Risk of Bone Fractures cohort. Sarcopenia was defined using three different definitions, including the Sarcopenia Definitions and Outcomes Consortium (SDOC), which includes grip strength and gait speed, while the revised European Working Group on Sarcopenia in Older People (EWGSOP2) and the Asian Working Group for Sarcopenia (AWGS) definitions include appendicular lean mass measured by dual-energy X-ray absorptiometry and grip strength. The results demonstrated that SDOC-defined sarcopenia was associated with a higher mortality risk, with increased risk of any fractures, and major osteoporotic fractures, whereas the EWGSOP2 and AWGS definitions were not associated with fracture risk. In summary, the study demonstrates that sarcopenia defined by SDOC, considering muscle function and strength, rather than lean mass, was the only investigated sarcopenia definition associated with fracture risk.
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| 49. |
- Gerdhem, Paul, et al.
(author)
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Associations between homocysteine, bone turnover, BMD, mortality, and fracture risk in elderly women
- 2007
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In: Journal of Bone and Mineral Research. - : Wiley. - 1523-4681 .- 0884-0431. ; 22:1, s. 127-134
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Journal article (peer-reviewed)abstract
- Homocysteine has been suggested to be a risk factor for fracture, but the causal relationship is not clear. In 996 women from the OPRA study, high homocysteine level was associated with high bone marker levels and low BMD at baseline. During a mean 7-year follow-up, high homocysteine level was associated with mortality, but no clear association to fracture risk existed.
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| 50. |
- Giangregorio, Lora M, et al.
(author)
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FRAX underestimates fracture risk in patients with diabetes
- 2012
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In: Journal of bone and mineral research. - : Wiley. - 1523-4681 .- 0884-0431. ; 27:2, s. 301-308
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Journal article (peer-reviewed)abstract
- The study objective was to determine whether diabetes is a risk factor for incident hip or major osteoporotic fractures independent of FRAX. Men and women with diabetes (N=3,518) and non-diabetics (N=36,085) age ≥50 years at the time of BMD testing (1990-2007) were identified in a large clinical database from Manitoba, Canada. FRAX probabilities were calculated and fracture outcomes to 2008 were established via linkage with a population-based data repository. Multivariable Cox proportional hazards models were used to determine if diabetes was associated with incident hip fractures or major osteoporotic fractures after controlling for FRAX risk factors. Mean 10-year probabilities of fracture were similar between groups for major fractures (diabetic 11.1±7.2 vs. non-diabetic 10.9±7.3, p-value=0.116) and hip fractures (diabetic 2.9±4.4 vs. non-diabetic 2.8±4.4, p-value=0.400). Diabetes was a significant predictor of subsequent major osteoporotic fracture (HR 1.61 [95% CI; 1.42-1.83]) after controlling for age, sex, medication use, and FRAX risk factors including BMD. Similar results were seen after adjusting for FRAX probability directly (HR 1.59 [95% CI; 1.40-1.79]). Diabetes was also associated with significantly higher risk for hip fractures (p-value<0.001). Higher mortality from diabetes attenuated but did not eliminate the excess fracture risk. FRAX underestimated observed major osteoporotic and hip fracture risk in diabetics (adjusted for competing mortality), but demonstrated good concordance with observed fractures for non-diabetics. We conclude that diabetes confers an increased risk of fracture that is independent of FRAX derived with BMD. This suggests that diabetes might be considered for inclusion in future iterations of FRAX. © 2011 American Society for Bone and Mineral Research.
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