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  • Agholme, Fredrik, et al. (författare)
  • Sclerostin Antibody Treatment Enhances Metaphyseal Bone Healing in Rats
  • 2010
  • Ingår i: JOURNAL OF BONE AND MINERAL RESEARCH. - : American Society for Bone and Mineral Research. - 0884-0431. ; 25:11, s. 2412-2418
  • Tidskriftsartikel (refereegranskat)abstract
    • Sclerostin is the product of the SOST gene Loss of-function mutations in the SOST gene result in a high bone-mass phenotype demonstrating that sclerostin is a negative regulator of bone mass Primarily expressed by osteocytes in bone sclerostin is reported to bind the LRP5/6 receptor thereby antagonizing canonical Wnt signaling and negatively regulating bone formation We therefore investigated whether systemic administration of a sclerostin neutralizing antibody would increase the regeneration of traumatized metaphyseal bone in rats Young male rats had a screw inserted in the proximal tibia and were divided into six groups given 25 mg/kg of sclerostin antibody or control twice a week subcutaneously for 2 or 4 weeks In four groups, the screws were tested for pull out strength At the time of euthanasia a similar screw also was inserted in the contralateral tibia and pull-out tested immediately Sclerostin antibody significantly increased the pull out force by almost 50% compared with controls after 2 and 4 weeks Also the screws inserted at the time of euthanasia showed increased pull out force Micro-computed tomography (mu CT) of the remaining two groups showed that the antibody led to a 30% increase in bone volume fraction in a region surrounding the screw There also was a general increase in trabecular thickness in cancellous bone Thus as measured by the amount of bone and its mechanical resistance the sclerostin antibody increased bone formation during metaphyseal repair but also in untraumatized bone
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  • Alfven, T, et al. (författare)
  • Cadmium exposure and distal forearm fractures
  • 2004
  • Ingår i: Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. - 0884-0431. ; 19:6, s. 900-905
  • Tidskriftsartikel (refereegranskat)
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  • Alfven, T, et al. (författare)
  • Low-level cadmium exposure and osteoporosis
  • 2000
  • Ingår i: Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. - : Wiley. - 0884-0431. ; 15:8, s. 1579-1586
  • Tidskriftsartikel (refereegranskat)
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  • Alfvén, Tobias, et al. (författare)
  • Low-level cadmium exposure and osteoporosis.
  • 2000
  • Ingår i: Journal of Bone and Mineral Research. - 0884-0431 .- 1523-4681. ; 15, s. 1579-1586
  • Tidskriftsartikel (refereegranskat)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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  • Andersson, G, et al. (författare)
  • TRACP as an osteopontin phosphatase
  • 2003
  • Ingår i: Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. - : Wiley. - 0884-0431. ; 18:10, s. 1912-1915
  • Tidskriftsartikel (refereegranskat)
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  • Aspenberg, Per, et al. (författare)
  • Teriparatide for Acceleration of Fracture Repair in Humans: A Prospective, Randomized, Double-Blind Study of 102 Postmenopausal Women With Distal Radial Fractures
  • 2010
  • Ingår i: JOURNAL OF BONE AND MINERAL RESEARCH. - : Wiley. - 0884-0431 .- 1523-4681. ; 25:2, s. 404-414
  • Tidskriftsartikel (refereegranskat)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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  • Aspenberg, Per, et al. (författare)
  • The bone morphogenetic proteins antagonist noggin inhibits membranous ossification
  • 2001
  • Ingår i: Journal of Bone and Mineral Research. - : Wiley. - 1523-4681 .- 0884-0431. ; 16:3, s. 497-500
  • Tidskriftsartikel (refereegranskat)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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  • Axelsson, Kristian F., et al. (författare)
  • Association Between Recurrent Fracture Risk and Implementation of Fracture Liaison Services in Four Swedish Hospitals: A Cohort Study
  • 2020
  • Ingår i: Journal of Bone and Mineral Research. - : Wiley. - 0884-0431 .- 1523-4681. ; 35:7, s. 1216-1223
  • Tidskriftsartikel (refereegranskat)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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  • Axelsson, Kristian F, et al. (författare)
  • Fracture risk after gastric bypass surgery – a retrospective cohort study
  • 2018
  • Ingår i: Journal of Bone and Mineral Research. - : Wiley-Blackwell Publishing Inc.. - 0884-0431 .- 1523-4681. ; 33:12, s. 2122-2131
  • Tidskriftsartikel (refereegranskat)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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  • Axelsson, Kristian F, 1973, et al. (författare)
  • The Importance of Recent Prevalent Fracture Site for Imminent Risk of Fracture - A Retrospective, Nationwide Cohort Study of Older Swedish Men and Women
  • 2023
  • Ingår i: Journal of Bone and Mineral Research. - : Wiley. - 0884-0431 .- 1523-4681. ; 38:6, s. 851-859
  • Tidskriftsartikel (refereegranskat)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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  • Baird, Denis A., et al. (författare)
  • Identification of Novel Loci Associated With Hip Shape : A Meta-Analysis of Genomewide Association Studies.
  • 2019
  • Ingår i: Journal of Bone and Mineral Research. - : Wiley-Blackwell. - 0884-0431 .- 1523-4681. ; 34:2, s. 241-251
  • Tidskriftsartikel (refereegranskat)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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  • Banefelt, Jonas, et al. (författare)
  • Total Hip Bone Mineral Density as an Indicator of Fracture Risk in Bisphosphonate-Treated Patients in a Real-World Setting
  • 2022
  • Ingår i: Journal of Bone and Mineral Research. - : Wiley. - 0884-0431 .- 1523-4681. ; 37:1, s. 52-58
  • Tidskriftsartikel (refereegranskat)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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  • Batkovskyte, D., et al. (författare)
  • Al-Gazali Skeletal Dysplasia Constitutes the Lethal End of ADAMTSL2-Related Disorders
  • 2023
  • Ingår i: Journal of Bone and Mineral Research. - : Wiley. - 0884-0431 .- 1523-4681. ; 38:5, s. 692-706
  • Tidskriftsartikel (refereegranskat)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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  • Benetou, Vassiliki, et al. (författare)
  • Fruit and Vegetable Intake and Hip Fracture Incidence in Older Men and Women : The CHANCES Project
  • 2016
  • Ingår i: Journal of Bone and Mineral Research. - : Wiley. - 0884-0431 .- 1523-4681. ; 31:9, s. 1743-1752
  • Tidskriftsartikel (refereegranskat)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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  • Boonen, Steven, et al. (författare)
  • Balloon Kyphoplasty for the Treatment of Acute Vertebral Compression Fractures: 2-Year Results From a Randomized Trial
  • 2011
  • Ingår i: Journal of Bone and Mineral Research. - : Wiley. - 1523-4681 .- 0884-0431. ; 26:7, s. 1627-1637
  • Tidskriftsartikel (refereegranskat)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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  • Buttazzoni, Christian, et al. (författare)
  • Does a childhood fracture predict low bone mass in young adulthood? - A 27-year prospective controlled study.
  • 2013
  • Ingår i: Journal of Bone and Mineral Research. - : Wiley. - 1523-4681 .- 0884-0431. ; 28:2, s. 351-359
  • Tidskriftsartikel (refereegranskat)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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  • Byberg, Liisa, et al. (författare)
  • Birth Weight is not Associated with Risk of Fracture : Results From Two Swedish Cohort Studies
  • 2014
  • Ingår i: Journal of Bone and Mineral Research. - : Wiley. - 0884-0431 .- 1523-4681. ; 29:10, s. 2152-2160
  • Tidskriftsartikel (refereegranskat)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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  • Byberg, Liisa, et al. (författare)
  • Fruit and vegetable intake and risk of hip fracture : A cohort study of Swedish men and women
  • 2015
  • Ingår i: Journal of Bone and Mineral Research. - : Wiley. - 0884-0431 .- 1523-4681. ; 30:6, s. 976-984
  • Tidskriftsartikel (refereegranskat)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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49.
  • Byberg, Liisa, et al. (författare)
  • Mediterranean Diet and Hip Fracture in Swedish Men and Women.
  • 2016
  • Ingår i: Journal of Bone and Mineral Research. - : Wiley. - 0884-0431 .- 1523-4681. ; 31:12, s. 2098-2105
  • Tidskriftsartikel (refereegranskat)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.
  •  
50.
  • Byberg, Liisa, et al. (författare)
  • Prediction of fracture risk in men : A cohort study
  • 2012
  • Ingår i: Journal of Bone and Mineral Research. - : Wiley. - 0884-0431 .- 1523-4681. ; 27:4, s. 797-807
  • Tidskriftsartikel (refereegranskat)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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