| 1. |
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| 2. |
- Albaik, Mai, et al.
(author)
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Bone mass in Saudi women aged 20–40 years : the association with obesity and vitamin D deficiency
- 2022
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In: Archives of Osteoporosis. - : Springer Science and Business Media LLC. - 1862-3522 .- 1862-3514. ; 17:1
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Journal article (peer-reviewed)abstract
- Summary: This study describes that low bone density is prevalent in premenopausal Saudi women, especially women of normal weight and vitamin D deficiency. Although BMD is higher in obese young women, this may not be beneficial later in life in conjunction with persistent vitamin D deficiency. Introduction: Not attaining peak bone mass is one crucial factor contributing to the risk of developing osteoporosis and suffering fractures in later life. The objectives of this study were to describe the normal range of bone mineral density (BMD) and bone mineral content (BMC) in premenopausal Saudi women in relation to obesity and vitamin D insufficiency. Methods: A cross-sectional study involving 312 healthy Saudi women aged 20–40. All women were clinically examined. BMD (g/cm2) and BMC (g) assessed at total body (TB), femoral neck (FN) and lumbar spine (LS) were performed using dual-energy X-ray absorptiometry (DXA). Obesity was defined as BMI ≥ 30 kg/m2 and vitamin D deficiency defined as 25(OH)D < 50 nmol/L. Results: Almost half of the studied women were obese, and the majority (86.2%) were deficient in vitamin D. Mean BMD in TB 1.060 ± 0.091, FN 0.918 ± 0.153 and LS 1.118 ± 0.123 g/cm2, while TB-BMC 2077 ± 272 g. When classified by BMI, the proportion with low bone density was 2–3 times higher among the normal weight compared to the obese women, p < 0.001. In the cohort overall, ~ 19% of these young premenopausal women had osteopenia or osteoporosis at the femoral neck, but 26% in normal weight, vitamin D deficient women. Conclusion: This study shows low bone density in premenopausal Saudi women, particularly those with normal weight. While obesity appears to confer some protection against vitamin D deficiency at this age, this is assumed to change in later life.
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| 3. |
- Bartosch, Patrik, et al.
(author)
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A “snap-shot” visual estimation of health and objectively measured frailty : capturing general health in aging older women
- 2022
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In: Aging clinical and experimental research. - : Springer Science and Business Media LLC. - 1594-0667 .- 1720-8319. ; 34:7, s. 1663-1671
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Journal article (peer-reviewed)abstract
- Background: In clinic, a subjective visual estimation of a patient’s general health often guides interventions, yet little is known of how this assessment relates to objectively measured frailty. Aims: To characterize the relationship between these two assessments and explore the implication of discordance. Methods: The study was performed in the OPRA cohort of 75-year old community-dwelling women (n = 1044). Visual perception of health (VPH) was estimated within 15 s from first sight and stratified into tertiles (poor/intermediate/good health). Frailty was measured using a frailty index (FI) (scored 0.0–1.0) and stratified into tertiles: ‘frail’ (≥ 0.22), ‘pre-frail’ (0.13–0-21) and ‘non-frail’ (≤ 0.12). Association between VPH and FI and with 10-year mortality was evaluated using Kaplan Meier curves and Cox proportional hazard models. Results: VPH and FI correlated, but was strongest in those perceived to be in poor health (rs = 0.424, p < 0.001). Approximately half of these women were also objectively frail (53.7%). Similarly, 50.7% perceived to be in good health were also objectively non-frail. However, for one in ten, perceived health was discordant with measured frailty. Subjective and objective measures were associated with mortality, but VPH lacked discrimination in healthier looking women (p = 0.372) compared to FI (p = 0.002). Discussion: Detecting pre-frailty is important to prevent or slow the transition into a frail state. The frailest can be identified with a visual estimation, but only objective frailty assessments can reliably identity pre-frailty. Conclusions: A visual estimation of health provides valuable complementary information on health, whereas objective assessment of frailty has a broader applicability for health in aging.
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| 4. |
- Bartosch, Patrik S., et al.
(author)
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Frailty and prediction of recurrent falls over 10 years in a community cohort of 75-year-old women
- 2020
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In: Aging clinical and experimental research. - : Springer Science and Business Media LLC. - 1594-0667 .- 1720-8319. ; 32:11, s. 2241-2250
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Journal article (peer-reviewed)abstract
- Background: Frailty captures the age-related declines in health leading to increased vulnerability, including falls which are commonplace in older women. The relationship between frailty and falls is complex, with one leading to the other in a vicious cycle. Aims: This study addresses the gap in understanding how patterns of frailty and falls propensity interact, particularly in those who have not yet entered the falls-frailty cycle. Methods: The Osteoporosis Risk Assessment cohort consists of 1044 community-dwelling women aged 75, with 10 years of follow-up. Investigations were performed and a frailty index constructed at baseline, 5 and 10 years. Falls were self-reported for each previous 12 months. Analysis was two-directional, firstly based on frailty status and second, based on falls status. Recurrent falls was the primary outcome. Results: Baseline frailty was a significant predictor of recurrent falls after 5 and 10 years [(OR 2.55 (1.62–3.99); 3.04 (1.63–5.67)]. Among women who had no history of falls at age 75, frailty was a stronger predictor of falls at 5 years [OR 3.06 (1.59–5.89)] than among women who had previously fallen. Discussion: Frailty is significantly associated with recurrent falls and most pronounced in those who are frail but have not yet fallen. Conclusions: This suggests that frailty should be an integral part of falls-risk assessment to improve identification of those at risk of becoming fallers.
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| 5. |
- Briggs, Andrew M., et al.
(author)
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Health systems strengthening to arrest the global disability burden : Empirical development of prioritised components for a global strategy for improving musculoskeletal health
- 2021
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In: BMJ Global Health. - : BMJ. - 2059-7908. ; 6:6
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Journal article (peer-reviewed)abstract
- Introduction Despite the profound burden of disease, a strategic global response to optimise musculoskeletal (MSK) health and guide national-level health systems strengthening priorities remains absent. Auspiced by the Global Alliance for Musculoskeletal Health (G-MUSC), we aimed to empirically derive requisite priorities and components of a strategic response to guide global and national-level action on MSK health. Methods Design: mixed-methods, three-phase design. Phase 1: qualitative study with international key informants (KIs), including patient representatives and people with lived experience. KIs characterised the contemporary landscape for MSK health and priorities for a global strategic response. Phase 2: scoping review of national health policies to identify contemporary MSK policy trends and foci. Phase 3: informed by phases 1-2, was a global eDelphi where multisectoral panellists rated and iterated a framework of priorities and detailed components/actions. Results Phase 1: 31 KIs representing 25 organisations were sampled from 20 countries (40% low and middle income (LMIC)). Inductively derived themes were used to construct a logic model to underpin latter phases, consisting of five guiding principles, eight strategic priority areas and seven accelerators for action. Phase 2: of the 165 documents identified, 41 (24.8%) from 22 countries (88% high-income countries) and 2 regions met the inclusion criteria. Eight overarching policy themes, supported by 47 subthemes, were derived, aligning closely with the logic model. Phase 3: 674 panellists from 72 countries (46% LMICs) participated in round 1 and 439 (65%) in round 2 of the eDelphi. Fifty-nine components were retained with 10 (17%) identified as essential for health systems. 97.6% and 94.8% agreed or strongly agreed the framework was valuable and credible, respectively, for health systems strengthening. Conclusion An empirically derived framework, co-designed and strongly supported by multisectoral stakeholders, can now be used as a blueprint for global and country-level responses to improve MSK health and prioritise system strengthening initiatives.
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| 6. |
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| 7. |
- Buchebner, David, et al.
(author)
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Association Between Hypovitaminosis D in Elderly Women and Long- and Short-Term Mortality-Results from the Osteoporotic Prospective Risk Assessment Cohort
- 2016
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In: Journal of the American Geriatrics Society. - : Wiley. - 0002-8614 .- 1532-5415. ; 64:5, s. 7-990
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Journal article (peer-reviewed)abstract
- OBJECTIVES: To investigate the association between low vitamin D levels (<50 nmol/L) and 10-year mortality in women aged 75 and older.DESIGN: Prospective with 15 years of follow-up.SETTING: Malmö, Sweden.PARTICIPANTS: Population-based cohort of 75-year-old women (N = 1,044).MEASUREMENTS: Serum 25-hydroxyvitamin D (25(OH)D) levels at age 75 (n = 1,011), 80 (n = 642), and 85 (n = 348) were categorized as low (<50 nmol/L), intermediate (50-75 nmol/L) and high (>75 nmol/L) at all ages. Hazard ratios (HRs) for all-cause mortality between ages 75 and 90 were calculated according to 25(OH)D category.RESULTS: Between ages 80 and 90, all-cause mortality (HR = 1.8, 95% confidence interval (CI) = 1.3-2.4, P < .001; adjusted for comorbidities (aHR) = 1.9, 95% CI = 1.4-2.6, P < .001) was significantly higher in women with low 25(OH)D levels than in those with high levels. Osteoporosis had the greatest effect on mortality, but even after excluding women with osteoporotic fracture during the risk of dying associated with low 25(OH)D remained greater (HR = 1.8, 95% CI = 1.2-2.7, P = .002; aHR = 1.7, 95% CI = 1.2-2.5, P = .006).CONCLUSION: In this observational study of women aged 75 and older, 25(OH)D levels of less than 50 nmol/L were associated with greater all-cause mortality for up to 10 years. This difference was at least partially independent of comorbidities and fracture, indicating that low 25(OH)D not only is an indicator of impaired health, but also plays a role in disease outcome.
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| 8. |
- Buchebner, David, et al.
(author)
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Association Between Vitamin D, Frailty, and Progression of Frailty in Community-Dwelling Older Women
- 2019
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In: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 104:12, s. 6139-6147
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Journal article (peer-reviewed)abstract
- CONTEXT: Vitamin D (25OHD) is involved in many physiological functions that decline with age, contributing to frailty and increased risk for negative health outcomes. Whether 25OHD is a long-term risk marker for frailty over a longer time and whether it is consistent with advancing age is unclear. OBJECTIVE: To investigate the association between 25OHD and frailty in older women followed for 10 years. DESIGN AND SETTING: Prospective, population-based, cohort study in Malmö, Sweden. PARTICIPANTS: Community-dwelling women, age 75 years (N = 1044) with reassessments at ages 80 (n = 715) and 85 (n = 382) years. METHODS: Frailty was quantified using a 10-variable frailty index. Women were categorized as 25OHD insufficient (<50 nmol/L) or sufficient (≥50 nmol/L). RESULTS: At ages 75 and 80 years, women with insufficient 25OHD were frailer than women with sufficient 25OHD (0.23 vs 0.18, P < 0.001; and 0.32 vs 0.25, P = 0.001, respectively). At age 80 years, 25OHD insufficiency was associated with subsequent frailty 5 years later (0.41 vs 0.32; P = 0.011). Accelerated progression of frailty was not associated with lower 25OHD levels, and 25OHD level >75 nmol/L was not additionally beneficial with regard to frailty. No association between 25OHD and frailty was observed at age 85 years. Within the frailty index, variables associated with 25OHD were related to muscle strength and function. CONCLUSION: In this study, 25OHD insufficiency was associated with increased frailty in all but the oldest old. This study supports the value of maintaining sufficient 25OHD levels for healthy aging.
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| 9. |
- Chan, Ding Cheng Derrick, et al.
(author)
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Consensus on best practice standards for Fracture Liaison Service in the Asia-Pacific region
- 2018
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In: Archives of Osteoporosis. - : Springer Science and Business Media LLC. - 1862-3522 .- 1862-3514. ; 13:1
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Journal article (peer-reviewed)abstract
- Summary: The Fracture Liaison Service (FLS) Consensus Meeting endorsed by the International Osteoporosis Foundation (IOF), Asian Federation of Osteoporosis Societies (AFOS), and Asia Pacific Osteoporosis Foundation (APOF) was hosted by the Taiwanese Osteoporosis Association on October 14, 2017. International and domestic experts reviewed the 13 Best Practice Framework (BPF) standards and concluded that all standards were generally applicable in the Asia-Pacific region and needed only minor modifications to fit the healthcare settings in the region. Purpose: To review and generate consensus on best practices of fracture liaison service (FLS) in the Asia-Pacific (AP) region. Methods: In October 2017, the Taiwanese Osteoporosis Association (TOA) invited experts from the AP region (n = 23), the Capture the Fracture Steering Committee (n = 2), and the USA (n = 1) to join the AP region FLS Consensus Meeting in Taipei. After two rounds of consensus generation, the recommendations on the 13 Best Practice Framework (BPF) standards were reported and reviewed by the attendees. Experts unable to attend the on-site meeting reviewed the draft, made suggestions, and approved the final version. Results: Because the number of FLSs in the region is rapidly increasing, experts agreed that it was timely to establish consensus on benchmark quality standards for FLSs in the region. They also agreed that the 13 BPF standards and the 3 levels of standards were generally applicable, but that some clarifications were necessary. They suggested, for example, that patient and family education be incorporated into the current standards and that communication with the public to promote FLSs be increased. Conclusions: The consensus on the 13 BPF standards reviewed in this meeting was that they were generally applicable and required only a few advanced clarifications to increase the quality of FLSs in the region.
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| 10. |
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| 11. |
- Ebeling, Peter R., et al.
(author)
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The Efficacy and Safety of Vertebral Augmentation : A Second ASBMR Task Force Report
- 2019
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In: Journal of Bone and Mineral Research. - : Wiley. - 0884-0431 .- 1523-4681. ; 34:1, s. 3-21
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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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| 12. |
- Ebrahimi, Parvaneh, et al.
(author)
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Epigenome-wide cross-tissue correlation of human bone and blood DNA methylation–can blood be used as a surrogate for bone?
- 2021
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In: Epigenetics. - : Informa UK Limited. - 1559-2294 .- 1559-2308. ; 16:1, s. 92-105
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Journal article (peer-reviewed)abstract
- Difficulty in obtaining bone tissue is an obstacle to studying epigenetics to understand gene–environment interactions, and their role in disease pathogenesis. Blood is an obvious alternative and in this proof of principle study, our aim was to systematically investigate whether blood is a viable surrogate for bone. We measured epigenome-wide DNA methylation at 850 K CpG sites in matched trabecular bone and peripheral blood collected from the same patients at the same time-point (n = 12 women; 66–85y), to investigate the between-tissue correspondence. What constituted a CpG site with corresponding methylation in both tissues was stringently defined. Only sites highly correlated (r2 > 0.74; FDR q-value <0.05) and at least 80% similarity in methylation level (Δβ <0.2) between paired samples were retained. In total, 28,549 CpG sites were similarly methylated in bone and blood. Between 33% and 49% of loci associated with bone phenotypes through GWAS were represented among these sites, and major pathways relevant to bone regulation were enriched. The results from this study indicate that blood can mirror the bone methylome and capture sites related to bone regulation. This study shows that in principal, peripheral blood is a feasible surrogate for bone tissue in DNA methylation investigations. As the first step, this will provide a platform for future studies in bone epigenetics, and possibly for larger-scale epidemiological studies.
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| 13. |
- Egund, Lisa, et al.
(author)
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High Prevalence of Osteoporosis in Men with Distal Radius Fracture : A Cross-Sectional Study of 233 Men
- 2016
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In: Calcified Tissue International. - : Springer Science and Business Media LLC. - 0171-967X .- 1432-0827. ; 99:3, s. 250-258
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Journal article (peer-reviewed)abstract
- Distal radius fracture is an early indicator of osteoporosis, yet little is known about men with this fracture and osteoporosis prevalence. The purpose of this cross-sectional, controlled study was to evaluate bone mineral density (BMD) in men, from working age to the elderly, with distal radius fracture. Recruitment was as follows: men who fractured during 1999–2000 were evaluated retrospectively in 2003 and men who fractured during 2003–2007 were followed prospectively for one year post-fracture. A total of 233 patients, response rate 40 %, were enrolled and compared with 643 controls. Fractures from all degrees of trauma were included. BMD was measured at femoral neck, total hip, and lumbar spine. Mean age at fracture was 52 years (21–88 years). Men aged 40–64 years had 5.4–6.7 % lower BMD at all sites compared to controls (p = 0.001) and in >65 years BMD was lower by 10.7–13.8 % (p <0.001), while not significant at 65 years: 23.3 vs 8.3 %) BMD did not differ with trauma level. Already from age 40, men with a distal radius fracture had lower BMD, the difference becoming more pronounced with increasing age. Also, the prevalence of osteoporosis was higher, surprisingly even in the youngest age group.
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| 14. |
- Ericsson, Ylva B., et al.
(author)
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Knee pain in young adult women- associations with muscle strength, body composition and physical activity
- 2021
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In: BMC Musculoskeletal Disorders. - : Springer Science and Business Media LLC. - 1471-2474. ; 22:1
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Journal article (peer-reviewed)abstract
- Background: Knee pain is studied mostly in older age groups, although in young adults it may be an indicator of future impaired musculoskeletal health. Therefore, the aim of this study was to examine the longitudinal association between knee pain and thigh muscle strength in young adult women and to explore the associations between muscle strength, body composition, physical activity and knee pain. Methods: The PEAK-25 cohort consists of women aged 25 at baseline (N=1064). At the 10-year follow-up n=728 attended for DXA-measured body composition and muscle strength assessment and n=797 answered the questionnaire on health and lifestyle. Independent samples t-test was used to compare women with and without knee pain, Spearman correlation was used to test the longitudinal association between strength and knee pain. Results: Knee pain was reported by one third of the women at follow-up (n=260, 33%), although physical activity levels were similar in those with and without pain (high level 50 vs 45 % (p= 0.18). Body composition differed, however. Women with knee pain had higher BMI (25.6 vs 24.1), fat mass index (9.2 vs 8.2) and % total body fat mass (34.7 vs 33.2). Simultaneously, they had lower % lean mass (total body 61.5 vs 62.8; legs 20.6 vs 21.0) and lower thigh muscle strength (extensors 184.9 vs 196.8, flexors 96.6 vs 100.9, p<0.05), but slightly higher hamstrings-to -quadriceps ratio (0.53 vs 0.51, p=0.04). Muscle strength at baseline weakly correlated with knee pain at follow-up (extensor rs= -0.04; flexor -0.02, p>0.2). Overweight women had higher absolute thigh muscle strength, but lower weight-adjusted strength than normal weight women (p<0.001). Leg lean mass explained 26-34% of the variation in muscle strength and adjustment for physical activity level had little effect. Conclusion: Knee pain is already common among women in their mid-thirties. Lower thigh muscle strength in the mid-twenties was not associated with future knee pain, however women with knee pain tended to have lower thigh muscle strength and a body composition of higher body fat combined with lower lean mass. Maintaining a healthy body composition and adequate thigh muscle strength may be beneficial for knee joint health.
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| 15. |
- Garg, Gaurav, et al.
(author)
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Glucose-dependent insulinotropic polypeptide (GIP) and GIP receptor (GIPR) genes : An association analysis of polymorphisms and bone in young and elderly women
- 2016
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In: Bone Reports. - : Elsevier BV. - 2352-1872. ; 4, s. 23-27
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Journal article (peer-reviewed)abstract
- Introduction: The gastro-intestinal hormone glucose-dependent insulinotropic polypeptide (GIP) potentiates glucose-induced insulin secretion, with bone anabolic effects through GIP receptor (GIPR) in animal models. We explore its potential in humans by analyzing association between polymorphisms (SNPs) in the GIP and GIPR genes with bone phenotypes in young and elderly women. Methods: Association between GIP (rs2291725) and GIPR (rs10423928) and BMD, bone mineral content (BMC), bone microarchitecture, fracture and body composition was analyzed in the OPRA (75y, n. =. 1044) and PEAK-25 (25y; n. =. 1061) cohorts and serum-GIP in OPRA. Results: The GIP receptor AA-genotype was associated with lower ultrasound values in young women (BUA p=0.011; SI p=0.030), with no association to bone phenotypes in the elderly. In the elderly, the GIP was associated with lower ultrasound (GG vs. AA; SOS padj=0.021) and lower femoral neck BMD and BMC after adjusting for fat mass (padj=0.016 and padj=0.03). In young women, neither GIPR nor GIP associated with other bone phenotypes including spine trabecular bone score. In the elderly, neither SNP associated with fracture. GIP was associated with body composition only in Peak-25; GIPR was not associated with body composition in either cohort. Serum-GIP levels (in elderly) were not associated with bone phenotypes, however lower levels were associated with the GIPR A-allele (β=-6.93; padj=0.03). Conclusions: This first exploratory association study between polymorphisms in GIP and GIPR in relation to bone phenotypes and serum-GIP in women at different ages indicates a possible, albeit complex link between glucose metabolism genes and bone, while recognizing that further studies are warranted.
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| 16. |
- Grundberg, Elin, et al.
(author)
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The impact of estradiol on bone mineral density is modulated by the specific estrogen receptor-alpha cofactor retinoblastoma-interacting zinc finger protein-1 insertion/deletion polymorphism.
- 2007
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In: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 92:6, s. 2300-6
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Journal article (peer-reviewed)abstract
- CONTEXT: Estrogens regulate bone mass by binding to the estrogen receptor (ER)-alpha as well as ER-beta. The specific ERalpha cofactor retinoblastoma-interacting zinc finger protein (RIZ)-1 enhances ERalpha function in the presence of estrogen. OBJECTIVE: The objective of the study was to determine whether a RIZ P704 insertion (+)/deletion (-) (indel) polymorphism modulates the impact of estradiol on bone mineral density (BMD) and study the association between the polymorphism and BMD in elderly subjects. DESIGN: This was a population-based, prospective, and cross-sectional study, the Swedish MrOS Study, and the Malmö OPRA Study, respectively. SETTING: The study was conducted at three academic medical centers: Sahlgrenska Academy in Gothenburg, Malmö University Hospital, and Uppsala University Hospital. PARTICIPANTS: In total, 4058 men and women, aged 69-81 yr, were randomly selected from population registries. MAIN OUTCOME MEASURES: BMD (grams per square centimeter) was measured at femoral neck, trochanter, lumbar spine, and total body. RESULTS: The RIZ P704(+/+) genotype was associated with low BMD in both women (femoral neck, P < 0.001; trochanter, P < 0.01; lumbar spine, P < 0.05; total body, P < 0.01) and men (lumbar spine, P < 0.05). However, the association between the polymorphism and BMD was dependent on estradiol status. The positive correlation between serum estradiol and BMD was significantly modulated by the genotype with a stronger correlation in the P704(+/+) group than the P704(-/-) group (r = 0.19 vs. r = 0.08, P < 0.05). CONCLUSIONS: These large-scale studies of elderly men and women indicate that the ERalpha cofactor RIZ gene has a prominent effect on BMD, and the P704 genotype modulates the impact of estradiol on BMD. Further studies are required to determine whether this polymorphism modulates the estrogenic response to estradiol treatment.
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| 17. |
- Hsu, Y. H., et al.
(author)
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Meta-Analysis of Genomewide Association Studies Reveals Genetic Variants for Hip Bone Geometry
- 2019
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In: Journal of Bone and Mineral Research. - : Wiley. - 0884-0431 .- 1523-4681. ; 34:7, s. 1284-1296
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Journal article (peer-reviewed)abstract
- Hip geometry is an important predictor of fracture. We performed a meta-analysis of GWAS studies in adults to identify genetic variants that are associated with proximal femur geometry phenotypes. We analyzed four phenotypes: (i) femoral neck length; (ii) neck-shaft angle; (iii) femoral neck width, and (iv) femoral neck section modulus, estimated from DXA scans using algorithms of hip structure analysis. In the Discovery stage, 10 cohort studies were included in the fixed-effect meta-analysis, with up to 18,719 men and women ages 16 to 93 years. Association analyses were performed with similar to 2.5 million polymorphisms under an additive model adjusted for age, body mass index, and height. Replication analyses of meta-GWAS significant loci (at adjusted genomewide significance [GWS], threshold p <= 2.6 x 10(-8)) were performed in seven additional cohorts in silico. We looked up SNPs associated in our analysis, for association with height, bone mineral density (BMD), and fracture. In meta-analysis (combined Discovery and Replication stages), GWS associations were found at 5p15 (IRX1 and ADAMTS16); 5q35 near FGFR4; at 12p11 (in CCDC91); 11q13 (near LRP5 and PPP6R3 (rs7102273)). Several hip geometry signals overlapped with BMD, including LRP5 (chr. 11). Chr. 11 SNP rs7102273 was associated with any-type fracture (p = 7.5 x 10(-5)). We used bone transcriptome data and discovered several significant eQTLs, including rs7102273 and PPP6R3 expression (p = 0.0007), and rs6556301 (intergenic, chr.5 near FGFR4) and PDLIM7 expression (p = 0.005). In conclusion, we found associations between several genes and hip geometry measures that explained 12% to 22% of heritability at different sites. The results provide a defined set of genes related to biological pathways relevant to BMD and etiology of bone fragility. (c) 2019 American Society for Bone and Mineral Research.
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| 18. |
- Ivaska, Kaisa K., et al.
(author)
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Bone Turnover Marker Profiling and Fracture Risk in Older Women : Fracture Risk from Age 75 to 90
- 2022
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In: Calcified Tissue International. - : Springer Science and Business Media LLC. - 0171-967X .- 1432-0827. ; 111:3, s. 288-299
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Journal article (peer-reviewed)abstract
- Purpose: A major challenge in osteoporosis is to identify individuals at high fracture risk. We investigated six bone turnover markers (BTMs) to determine association with specific fracture types; the time-frame for risk prediction and whether these are influenced by age at assessment. Methods: Population-based OPRA cohort (n = 1044) was assessed at ages 75, 80, 85 and fractures documented for up to 15 years. Six BTMs were analyzed at each time-point (N-terminal propeptide of type I collagen, PINP; total osteocalcin, OC; bone-specific alkaline phosphatase, BALP; C-terminal telopeptide of type I collagen, CTX; tartrate-resistant acid phosphatase 5b, TRAcP5b; urinary osteocalcin). Hazard ratios (HR) for any, major osteoporotic, vertebral and hip fractures were calculated as short (1, 2, 3 years) and long-term risk (5, 10, 15 years). Results: At 75 year, high CTX levels were associated with an increased risk of all fractures, including major osteoporotic fractures, across most time-frames (HRs ranging: 1.28 to 2.28). PINP was not consistently associated. Urinary osteocalcin was consistently associated with elevated short-term risk (HRs ranging: 1.83–2.72). Other BTMs were directionally in accordance, though not all statistically significant. BTMs were not predictive for hip fractures. Association of all BTMs attenuated over time; at 80 year none were associated with an increased fracture risk. Conclusion: CTX, urinary OC and TRAcP5b are predictive for fracture in a 1 to 3 year, perspective, whereas in the long-term or above age 80 years, BTMs appear less valuable. Resorption markers, particularly CTX, were more consistently associated with fracture risk than formation markers in the very elderly.
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| 19. |
- Jensen, Vivi Fh, et al.
(author)
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Differential expression of the inflammatory ciita gene may be accompanied by altered bone properties in intact sex steroid-deficient female rats
- 2023
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In: BMC Research Notes. - 1756-0500. ; 16:1
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Journal article (peer-reviewed)abstract
- Objective: The class II transactivator (CIITA), encoded by the CIITA gene, controls expression of immune response regulators, which affect bone homeostasis. Previously, we investigated a functional CIITA polymorphism in elderly women. Women carrying the allele associated with lower CIITA levels displayed higher bone mineral density (BMD), but also higher bone loss. The present exploratory study in a rat model sought to investigate effects of differential expression of Ciita on bone structural integrity and strength. Two strains DA (normal-to-high expression) and DA.VRA4 (lower expression) underwent ovariectomy (OVX) or sham-surgery at ~ 14-weeks of age (DA OVX n = 8, sham n = 4; DA.VRA4 OVX n = 10, sham n = 2). After 16-weeks, femoral BMD and bone mineral content (BMC) were measured and morphometry and biomechanical testing performed. Results: In DA.VRA4 rats, BMD/BMC, cross-sectional area and biomechanical properties were lower. Ciita expression was accompanied by OVX-induced changes to cross-sectional area and femoral shaft strength; DA rats had lower maximum load-to-fracture. Thus, while lower Ciita expression associated with lower bone mass, OVX induced changes to structural and mechanical bone properties were less pronounced. Conclusion: The data tentatively suggests association between Ciita expression and structural and mechanical bone properties, and a possible role in bone changes resulting from estrogen deficiency.
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| 20. |
- Jensen, Vivi F.H., et al.
(author)
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Changes in bone mass associated with obesity and weight loss in humans : Applicability of animal models
- 2021
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In: Bone. - : Elsevier BV. - 8756-3282. ; 145
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Research review (peer-reviewed)abstract
- The implications of obesity and weight loss for human bone health are not well understood. Although the bone changes associated with weight loss are similar in humans and rodents, that is not the case for obesity. In humans, obesity is generally associated with increased bone mass, an outcome which is exacerbated by advanced age and menopause. In rodents, by contrast, bone mass decreases in proportion to severity and duration of obesity, and is influenced by sex, age and mechanical load. Despite these discrepancies, rodents are frequently used to model the situation in humans. In this review, we summarise the existing knowledge of the effects of obesity and weight loss on bone mass in humans and rodents, focusing on the translatability of findings from animal models. We then describe how animal models should be used to broaden the understanding of the relationship between obesity, weight loss, and skeletal health in humans. Specifically, we highlight the aspects of study design that should be considered to optimise translatability of the rodent models of obesity and weight loss. Notably, the sex, age, and nutritional status of the animals should ideally match those of interest in humans. With these caveats in mind, and depending on the research question asked, our review underscores that animal models can provide valuable information for obesity and weight-management research.
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| 21. |
- Jensen, Vivi F.H., et al.
(author)
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Inner histopathologic changes and disproportionate zone volumes in foetal growth plates following gestational hypoglycaemia in rats
- 2020
-
In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1
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Journal article (peer-reviewed)abstract
- Maternal hypoglycaemia throughout gestation until gestation day (GD)20 delays foetal growth and skeletal development. While partially prevented by return to normoglycaemia after completed organogenesis (GD17), underlying mechanisms are not fully understood. Here, we investigated the pathogenesis of these changes and significance of maternal hypoglycaemia extending beyond organogenesis in non-diabetic rats. Pregnant rats received insulin-infusion until GD20 or GD17, with sacrifice on GD20. Hypoglycaemia throughout gestation increased maternal corticosterone levels, which correlated with foetal levels. Growth plates displayed central histopathologic changes comprising disrupted cellular organisation, hypertrophic chondrocytes, and decreased cellular density; expression of pro-angiogenic factors, HIF-1α and VEGF-A increased in surrounding areas. Disproportionately decreased growth plate zone volumes and lower expression of the structural protein MATN-3 were seen, while bone ossification parameters were normal. Ending maternal/foetal hypoglycaemia on GD17 reduced incidence and severity of histopathologic changes and with normal growth plate volume. Compromised foetal skeletal development following maternal hypoglycaemia throughout gestation is hypothesised to result from corticosterone-induced hypoxia in growth plates, where hypoxia disrupts chondrocyte maturation and growth plate structure and volume, decreasing long bone growth. Maternal/foetal hypoglycaemia lasting only until GD17 attenuated these changes, suggesting a pivotal role of glucose in growth plate development.
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| 22. |
- Khan, Jalaluddin A., et al.
(author)
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Osteoporosis knowledge and awareness among university students in Saudi Arabia
- 2019
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In: Archives of Osteoporosis. - : Springer Science and Business Media LLC. - 1862-3522 .- 1862-3514. ; 14:1
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Journal article (peer-reviewed)abstract
- Awareness and knowledge about any disease is the first step to prevent and treat it, so this study evaluates osteoporosis awareness and knowledge in university students. Our results showed a high awareness and good knowledge of osteoporosis. Females were better informed than males. Knowledge increased with increasing education level. PURPOSE: Osteoporosis is a worldwide health problem, including Saudi Arabia where vitamin D deficiency is common. Prevention of osteoporosis must begin by increasing awareness of the disease from a young age. This study aimed to assess awareness and knowledge of osteoporosis among young adults (18-30 years) attending Saudi universities, exploring the relationship between education and gender and the sources of information in this age group. METHODS: A cross-sectional survey was conducted in 337 students (176 females; 161 males) randomly selected from four Saudi universities during January-December 2017. Education level ranged from preparatory year to undergraduate and postgraduate levels. A self-reported questionnaire was designed to assess awareness and knowledge of osteoporosis across several domains, including risk factors for the disease, prevalence, symptoms, prevention, and treatment. RESULTS: Overall, 92% of students had some awareness of osteoporosis through a variety of sources, predominantly via friends. Just over half of all students had a good or high knowledge level overall (53.4 ± 16.6%). Knowledge score correlated with education (r2 = 0.28) and gender (r2 = 0.27); p < 0.0001. Females were better informed than males (57.7 ± 15.4% vs 48.8 ± 16.8%; p < 0.0001). Knowledge increased with increasing education level (preparatory year (47.8 ± 15.3%), undergraduate (53.5 ± 16.5%), and postgraduate (61.8 ± 15.8%); all p < 0.0001). CONCLUSION: Knowledge of osteoporosis was good among university students in Saudi Arabia, higher in females and with increasing years of education. Overall, students were more knowledgeable about risk factors compared to other aspects such as symptoms, prevention, or treatment of osteoporosis.
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| 23. |
- Lagerholm, Sofia, et al.
(author)
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Genetic regulation of bone traits is influenced by sex and reciprocal cross in F(2) progeny from GK and F344 rats.
- 2009
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In: Journal of bone and mineral research. - : Wiley. - 1523-4681 .- 0884-0431. ; 24:6, s. 1066-74
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Journal article (peer-reviewed)abstract
- A genome-wide linkage analysis to identify quantitative trait loci (QTLs) for bone phenotypes was performed in an F(2) intercross of inbred spontaneously type 2 diabetic GK and normoglycemic F344 rats (108 males and 98 females). The aim of the study was to locate genome regions with candidate genes affecting trabecular and cortical bone and to investigate the effects of sex and reciprocal cross. pQCT was used to determine tibial bone phenotypes in the F(2) rats, comprising reciprocal crosses with divergent mitochondrial (mt) DNA. Sex and reciprocal cross-separated QTL analyses were performed followed by assessment of specific interactions. Four genome-wide significant QTLs linked to either cortical vBMD, tibia length, body length, or metaphyseal area were identified in males on chromosomes (chr) 1, 8, and 15. In females, three significant QTLs linked to cortical BMC or metaphyseal total vBMD were identified on chr 1 and 2. Several additional suggestive loci for trabecular and cortical traits were detected in both males and females. Four female-specific QTLs on chr 2, 3, 5, and 10 and four reciprocal cross-specific QTLs on chr 1, 10, and 18 were identified, suggesting that both sex and mt genotype influence the expression of bone phenotypes.
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| 24. |
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| 25. |
- Malmgren, Linnea, et al.
(author)
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Impaired selective renal filtration captured by eGFRcysC/eGFRcrea ratio is associated with mortality in a population based cohort of older women
- 2022
-
In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 12:1
-
Journal article (peer-reviewed)abstract
- Deranged renal filtration of mid-sized (5-30 kDa) compared to smaller molecules (< 0.9 kDa) results in increased plasma levels of cystatin C (cysC) compared to creatinine resulting in a low eGFRcysC/eGFRcrea ratio. A ratio below 0.6 or 0.7, is termed shrunken pore syndrome (SPS), which in patient based studies is associated with mortality. Reference values for eGFRcysC/eGFRcrea ratio, the prevalence of SPS and the consequence of low eGFRcysC/eGFRcrea ratio in the general, elderly population are unknown. 75-yr old women (n = 849) from the population-based OPRA cohort, followed for 10-years had eGFR calculated with CKD-EPI study equation, and eGFRcysC/eGFRcrea ratio calculated. Mortality risk (HR [95% CI]) was estimated. Women with sarcopenia or on glucocorticoids were excluded. Almost 1 in 10 women (9%) had eGFRcysC/eGFRcrea ratio < 0.6 at age 75 and this did not increase appreciably with age. Women with ratio < 0.6 had higher 10-yr mortality risk compared with ratios > 0.9 (HRadj 1.6 [95% CI 1.1-2.5]). In elderly women eGFRcysC/eGFRcrea ratio < 0.6 is common and associated with increased mortality. Our results confirm patient-based findings, suggesting that identifying individuals with SPS may be clinically relevant to assessing mortality risk in the elderly.
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| 26. |
- Malmgren, Linnea, et al.
(author)
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Longitudinal Changes in Kidney Function Estimated from Cystatin C and Its Association with Mortality in Elderly Women
- 2020
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In: Nephron. - : S. Karger AG. - 1660-8151 .- 2235-3186. ; 144:6, s. 290-298
-
Journal article (peer-reviewed)abstract
- Background/Aims: Prospective data on age-related changes in kidney function are required, especially since the current Kidney Disease Improving Global Outcomes (KDIGO) definition has been suggested to classify a large number of elderly people with CKD. Objective: This study, a complement to our previous Cr-based study in the same cohort, is aimed at evaluating cystatin C (cysC)-based changes in kidney function during aging in older women and analyzing the association between CKD and mortality through 10 years of follow-up. Methods: cysC was available in 981 women from the Osteoporosis Prospective Risk Assessment (OPRA) cohort, all aged 75 years on entry. Reinvestigations were made after 5 (n = 685) and 10 years (n = 365). Kidney function was estimated (estimated glomerular filtration rate [eGFR]) using Chronic Kidney Disease Epidemiology Collaboration cysC and Caucasian, Asian, Pediatric, and Adult cysC equations and the change in function calculated. Women were staged equivalent to CKD stage 1, 2, 3a, or 3b-5 according to the KDIGO classification. Mortality risk was estimated for 5-year or 10-year follow-up time using Cox proportional hazard analyses (reference category, CKD stages 1 and 2). Results: Mortality risk for women with the worst kidney function (CKD stages 3b-5) increased during both 5-year follow-up times compared to that for women in stages 1 and 2 (age 75-80 years: adjusted Hazard Ratio [HRadj] 3.9, 95% confidence interval [CI] 2.3-6.5; age 80-85 years: HRadj 1.7, 95% CI 1.0-2.7). In contrast, women in stage 3a had increased risk only in the first 5-year follow-up (HRadj 1.7, 95% CI 1.0-3.0, age 75-80 years). Change in kidney function amounted to a loss of 1.9 (±1.4) mL/min/1.73 m2 per year during the 10-year follow-up, and at age 85 years, 4 of every 5 women had an eGFR equivalent to CKD. Conclusion: In the future, an age-adapted definition of CKD, lowering the threshold for CKD in the elderly, may be beneficial to avoid overdiagnosis of CKD.
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| 27. |
- Medina-Gomez, C., et al.
(author)
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Life-Course Genome-wide Association Study Meta-analysis of Total Body BMD and Assessment of Age-Specific Effects
- 2018
-
In: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297. ; 102:1, s. 88-102
-
Journal article (peer-reviewed)abstract
- Bone mineral density (BMD) assessed by DXA is used to evaluate bone health. In children, total body (TB) measurements are commonly used; in older individuals, BMD at the lumbar spine (LS) and femoral neck (FN) is used to diagnose osteoporosis. To date, genetic variants in more than 60 loci have been identified as associated with BMD. To investigate the genetic determinants of TB-BMD variation along the life course and test for age-specific effects, we performed a meta-analysis of 30 genome-wide association studies (GWASs) of TB-BMD including 66,628 individuals overall and divided across five age strata, each spanning 15 years. We identified variants associated with TB-BMD at 80 loci, of which 36 have not been previously identified; overall, they explain approximately 10% of the TB-BMD variance when combining all age groups and influence the risk of fracture. Pathway and enrichment analysis of the association signals showed clustering within gene sets implicated in the regulation of cell growth and SMAD proteins, overexpressed in the musculoskeletal system, and enriched in enhancer and promoter regions. These findings reveal TB-BMD as a relevant trait for genetic studies of osteoporosis, enabling the identification of variants and pathways influencing different bone compartments. Only variants in ESR1 and close proximity to RANKL showed a clear effect dependency on age. This most likely indicates that the majority of genetic variants identified influence BMD early in life and that their effect can be captured throughout the life course. © 2017 American Society of Human Genetics
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| 28. |
- Mitchell, Adam, et al.
(author)
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Pro-Inflammatory Proteins Associated with Frailty and Its Progression—A Longitudinal Study in Community-Dwelling Women
- 2023
-
In: Journal of Bone and Mineral Research. - 0884-0431. ; 38:8, s. 1076-1091
-
Journal article (peer-reviewed)abstract
- The complex pathophysiology underlying biological aging creates challenges for identifying biomarkers associated with frailty. This longitudinal, nontargeted proteomics study aimed to identify proteins associated with frailty, particularly the change from nonfrail to frail. The population-based Osteoporosis Prospective Risk Assessment cohort includes women all of whom are 75 years old at inclusion (n = 1044) and reassessed at 80 years (n = 715) and 85 years (n = 382). A deficits in health frailty index (FI) and 92 plasma proteins (Olink CVD-II panel) were available at all ages. The identical age facilitated differentiating chronological and biological aging. Bidirectional analyses, performed cross-sectionally and longitudinally, used regression models controlled for false discovery rate (FDR), across 5- and 10-year time windows and longitudinal mixed models. Frailty outcomes were frailty index, frailty status (frail defined as FI ≥ 0.25), change in frailty index, and change in frailty status, together with protein expression or change in protein expression. Elevated levels of 32 proteins were positively associated with the FI, cross-sectionally at all ages (range: β-coefficients 0.22–2.06; FDR 0.021–0.024), of which 18 were also associated with frailty status (range: odds ratios 1.40–5.77; FDR 0.022–0.016). Based on the accrued data, eight core proteins (CD4, FGF23, Gal-9, PAR-1, REN, TNFRSF10A TNFRSF11A, and TNFRSF10B) are proposed. A one-unit change in the FI was additively associated with increased protein expression over 5 and 10 years (range: β-coefficients 0.52–1.59; p < 0.001). Increments in baseline FI consistently associated with a change in protein expression over time (5 years, β-range 0.05–1.35; 10 years, β-range 0.51–1.48; all p < 0.001). A one-unit increase in protein expression was also associated with an increased probability of being frail (FI ≥ 0.25) (β-range: 0.14–0.61). Mirroring the multisystem deterioration that typifies frailty, the proteins and their associated biological pathways reflect pathologies, including the renal system, skeletal homeostasis, and TRAIL-activated apoptotic signaling. The core proteins are compelling candidates for understanding the development and progression of frailty with advancing age, including the intrinsic musculoskeletal component.
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| 29. |
- Paulin, Tine Kolenda, et al.
(author)
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Osteosarcopenia : Prevalence and 10-Year Fracture and Mortality Risk – A Longitudinal, Population-Based Study of 75-Year-Old Women
-
In: Calcified Tissue International. - 0171-967X.
-
Journal article (peer-reviewed)abstract
- Osteosarcopenia is the coexistence of low bone mass and sarcopenia. In older women, its prevalence is not well described, and it is unknown if sarcopenia is additive to low bone mass for fracture and mortality risk. The study investigated prevalence of osteosarcopenia and if osteosarcopenia is associated with higher fracture and mortality risk than low bone mass alone in older community-dwelling women. The longitudinal, population-based OPRA Cohort (n = 1044), all aged 75 at inclusion, followed for 10 years. Using WHO and EWGSOP2 definitions for low bone mass (T-score < −1.0 femoral neck) and sarcopenia (knee strength; appendicular lean muscle mass) women were categorized (1) Normal, (2) Low bone mass (LBM), and 3) Osteosarcopenia (probable; confirmed). Risk of hip, major osteoporotic fracture, and mortality were estimated. Osteosarcopeniaconfirmed prevalence increased from age 75 to 80 and 85 from 3.0% (29/970) to 4.9% (32/656) to 9.2% (33/358) but prevalence is potentially 2–4 times higher (11.8%, 13.4%, 20.3%) based on osteosarcopeniaprobable. Having osteosarcopeniaprobable significantly increased 10-year risk of hip fracture (HRadj 2.67 [1.34–5.32]), major osteoporotic fracture (HRadj 2.04 [1.27–3.27]), and mortality (HRadj 1.91 [1.21–3.04]). In contrast, LBM increased osteoporotic fracture risk (HRadj 2.08 [1.46–2.97], but not hip fracture (HRadj 1.62 [0.92–2.85]) or mortality (HRadj 0.94 [0.64–1.38]). Median time-to-hip fracture was 7.6 years (normal), 6.0 years (LBM), and 5.7 years (osteosarcopeniaprobable). Prevalence of confirmed osteosarcopenia is almost 10% at age 85. Probable osteosarcopenia significantly increased risk of hip and major osteoporotic fractures and mortality more so than low bone mass alone.
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| 30. |
- Prakash, Jai, et al.
(author)
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Analysis of RAMP3 gene polymorphism with body composition and bone density in young and elderly women
- 2019
-
In: Gene: X. - : Elsevier BV. - 2590-1583. ; 2
-
Journal article (peer-reviewed)abstract
- Background and aim: The Receptor Activity Modifying Proteins (RAMPs) are a group of accessory proteins, of which there are three in humans, that interact with a number of G-protein coupled receptors (GPCR) and play various roles in regulation of endocrine signaling. Studies in RAMP3 knockout (KO) mice reveal an age related phenotype with altered metabolic regulation and high bone mass. To translate these findings into a clinically relevant perspective, we investigated the association between RAMP3 gene variants, body composition and bone phenotypes in two population-based cohorts of Swedish women. Methods: Five single nucleotide polymorphisms (SNP) in the vicinity of the RAMP3 gene were genotyped in the PEAK-25 cohort (n = 1061; 25 years) and OPRA (n = 1044; 75 years). Bone mineral density (BMD), fat mass and lean mass (total body; regional) were measured by DXA at baseline, 5 and 10 year follow-up. Results: BMD did not differ with RAMP3 genotype in either cohort, although fracture risk was increased in the elderly women (OR 2.695 [95% CI 1.514–4.801]). Fat mass tended to be higher with RAMP3 SNPs; although only in elderly women. In the young women, changes in BMI and fat mass between ages 25–35 differed by genotype (p = 0.001; p < 0.001). Conclusion: Variation in RAMP3 may contribute to age-related changes in body composition and risk of fracture.
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| 31. |
- Robinson-Cohen, Cassianne, et al.
(author)
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Genetic Variants Associated with Circulating Fibroblast Growth Factor 23
- 2018
-
In: Journal of the American Society of Nephrology. - : AMER SOC NEPHROLOGY. - 1046-6673 .- 1533-3450. ; 29:10, s. 2583-2592
-
Journal article (peer-reviewed)abstract
- Background: Fibroblast growth factor 23 (FGF23), a bone-derived hormone that regulates phosphorus and vitamin D metabolism, contributes to the pathogenesis of mineral and bone disorders in CKD and is an emerging cardiovascular risk factor. Central elements of FGF23 regulation remain incompletely understood; genetic variation may help explain interindividual differences.Methods: We performed a meta-analysis of genome-wide association studies of circulating FGF23 concentrations among 16,624 participants of European ancestry from seven cohort studies, excluding participants with eGFR<30 ml/min per 1.73 m(2) to focus on FGF23 under normal conditions. We evaluated the association of single-nucleotide polymorphisms (SNPs) with natural log-transformed FGF23 concentration, adjusted for age, sex, study site, and principal components of ancestry. A second model additionally adjusted for BMI and eGFR.Results: We discovered 154 SNPs from five independent regions associated with FGF23 concentration. The SNP with the strongest association, rs17216707 (P=3.0x10(-24)), lies upstream of CYP24A1, which encodes the primary catabolic enzyme for 1,25-dihydroxyvitamin D and 25-hydroxyvitamin D. Each additional copy of the T allele at this locus is associated with 5% higher FGF23 concentration. Another locus strongly associated with variations in FGF23 concentration is rs11741640, within RGS14 and upstream of SLC34A1 (a gene involved in renal phosphate transport). Additional adjustment for BMI and eGFR did not materially alter the magnitude of these associations. Another top locus (within ABO, the ABO blood group transferase gene) was no longer statistically significant at the genome-wide level.Conclusions: Common genetic variants located near genes involved in vitamin D metabolism and renal phosphate transport are associated with differences in circulating FGF23 concentrations.
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| 32. |
- Rodriguez, Alexander J., et al.
(author)
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Pain, Quality of Life, and Safety Outcomes of Kyphoplasty for Vertebral Compression Fractures : Report of a Task Force of the American Society for Bone and Mineral Research
- 2017
-
In: Journal of Bone and Mineral Research. - : Wiley. - 0884-0431. ; 32:9, s. 1935-1944
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Journal article (peer-reviewed)abstract
- The relative efficacy and harms of balloon kyphoplasty (BK) for treating vertebral compression fractures (VCF) are uncertain. We searched multiple electronic databases to March 2016 for randomized and quasi-randomized controlled trials comparing BK with control treatment (nonsurgical management [NSM], percutaneous vertebroplasty [PV], KIVA VCF treatment system [Benvenue Medical, Inc., Santa Clara, CA, USA], vertebral body stenting, or other) in adults with VCF. Outcomes included back pain, back disability, quality of life, new VCF, and adverse events (AEs). One reviewer extracted data, a second checked accuracy, and two rated risk of bias (ROB). Mean differences and 95% confidence intervals (CIs) were calculated using inverse-variance models. Risk ratios of new VCF and AE were calculated using Mantel-Haenszel models. Ten unique trials enrolled 1837 participants (age range, 61 to 76 years; 74% female), all rated as having high or uncertain ROB. Versus NSM, BK was associated with greater reductions in pain, back-related disability, and better quality of life (k = 1 trial) that appeared to lessen over time, but were less than minimally clinically important differences. Risk of new VCF at 3 and 12 months was not significantly different (k = 2 trials). Risk of any AE was increased at 1 month (RR = 1.73; 95% CI, 1.36 to 2.21). There were no significant differences between BK and PV in back pain, back disability, quality of life, risk of new VCF, or any AE (k = 1 to 3 trials). Limitations included lack of a BK versus sham comparison, availability of only one RCT of BK versus NSM, and lack of study blinding. Individuals with painful VCF experienced symptomatic improvement compared with baseline with all interventions. The clinical importance of the greater improvements with BK versus NSM is unclear, may be due to placebo effect, and may not counterbalance short-term AE risks. Outcomes appeared similar between BK and other surgical interventions. Well-conducted randomized trials comparing BK with sham would help resolve remaining uncertainty about the relative benefits and harms of BK.
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| 33. |
- Tarantino, Umberto, et al.
(author)
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Gaps and alternative surgical and non-surgical approaches in the bone fragility management : an updated review
- 2022
-
In: Osteoporosis International. - : Springer Science and Business Media LLC. - 0937-941X .- 1433-2965. ; 33:12, s. 2467-2478
-
Research review (peer-reviewed)abstract
- Osteoporotic fractures are one of the major problems facing healthcare systems worldwide. Undoubtedly, fragility fractures of the hip represent a far greater burden in terms of morbidity, mortality, and healthcare costs than other fracture sites. However, despite the significant impact on the health and quality of life of older adults, there is a general lack of awareness of osteoporosis, which results in suboptimal care. In fact, most high-risk individuals are never identified and do not receive adequate treatment, leading to further fragility fractures and worsening health status. Furthermore, considering the substantial treatment gap and the proven cost-effectiveness of fracture prevention programs such as Fracture Liaison Services, urgent action is needed to ensure that all individuals at high risk of fragility fracture are adequately assessed and treated. Based on this evidence, the aim of our review was to (i) provide an overview and comparison of the burden and management of fragility fractures, highlighting the main gaps, and (ii) highlight the importance of using alternative approaches, both surgical and non-surgical, with the aim of implementing early prevention of osteoporotic fractures and improving the management of osteoporotic patients at imminent and/or very high risk of fracture.
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| 34. |
- van Meurs, Joyce B, et al.
(author)
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Large-scale analysis of association between LRP5 and LRP6 variants and osteoporosis.
- 2008
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In: JAMA : the journal of the American Medical Association. - Chicago : American Medical Association (AMA). - 1538-3598 .- 0098-7484. ; 299:11, s. 1277-90
-
Journal article (peer-reviewed)abstract
- CONTEXT: Mutations in the low-density lipoprotein receptor-related protein 5 (LRP5) gene cause rare syndromes characterized by altered bone mineral density (BMD). More common LRP5 variants may affect osteoporosis risk in the general population. OBJECTIVE: To generate large-scale evidence on whether 2 common variants of LRP5 (Val667Met, Ala1330Val) and 1 variant of LRP6 (Ile1062Val) are associated with BMD and fracture risk. DESIGN AND SETTING: Prospective, multicenter, collaborative study of individual-level data on 37,534 individuals from 18 participating teams in Europe and North America. Data were collected between September 2004 and January 2007; analysis of the collected data was performed between February and May 2007. Bone mineral density was assessed by dual-energy x-ray absorptiometry. Fractures were identified via questionnaire, medical records, or radiographic documentation; incident fracture data were available for some cohorts, ascertained via routine surveillance methods, including radiographic examination for vertebral fractures. MAIN OUTCOME MEASURES: Bone mineral density of the lumbar spine and femoral neck; prevalence of all fractures and vertebral fractures. RESULTS: The Met667 allele of LRP5 was associated with reduced lumbar spine BMD (n = 25,052 [number of participants with available data]; 20-mg/cm2 lower BMD per Met667 allele copy; P = 3.3 x 10(-8)), as was the Val1330 allele (n = 24,812; 14-mg/cm2 lower BMD per Val1330 copy; P = 2.6 x 10(-9)). Similar effects were observed for femoral neck BMD, with a decrease of 11 mg/cm2 (P = 3.8 x 10(-5)) and 8 mg/cm2 (P = 5.0 x 10(-6)) for the Met667 and Val1330 alleles, respectively (n = 25 193). Findings were consistent across studies for both LRP5 alleles. Both alleles were associated with vertebral fractures (odds ratio [OR], 1.26; 95% confidence interval [CI], 1.08-1.47 for Met667 [2001 fractures among 20 488 individuals] and OR, 1.12; 95% CI, 1.01-1.24 for Val1330 [1988 fractures among 20,096 individuals]). Risk of all fractures was also increased with Met667 (OR, 1.14; 95% CI, 1.05-1.24 per allele [7876 fractures among 31,435 individuals)]) and Val1330 (OR, 1.06; 95% CI, 1.01-1.12 per allele [7802 fractures among 31 199 individuals]). Effects were similar when adjustments were made for age, weight, height, menopausal status, and use of hormone therapy. Fracture risks were partly attenuated by adjustment for BMD. Haplotype analysis indicated that Met667 and Val1330 variants both independently affected BMD. The LRP6 Ile1062Val polymorphism was not associated with any osteoporosis phenotype. All aforementioned associations except that between Val1330 and all fractures and vertebral fractures remained significant after multiple-comparison adjustments. CONCLUSIONS: Common LRP5 variants are consistently associated with BMD and fracture risk across different white populations. The magnitude of the effect is modest. LRP5 may be the first gene to reach a genome-wide significance level (a conservative level of significance [herein, unadjusted P < 10(-7)] that accounts for the many possible comparisons in the human genome) for a phenotype related to osteoporosis.
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| 35. |
- Woolf, Anthony D., et al.
(author)
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Clinical advances – from bench to bedside
- 2020
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In: Best Practice and Research: Clinical Rheumatology. - : Elsevier BV. - 1521-6942. ; 34:5
-
Research review (peer-reviewed)
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| 36. |
- Woolf, Anthony D., et al.
(author)
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Musculoskeletal health – The case for action
- 2020
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In: Best Practice and Research: Clinical Rheumatology. - : Elsevier BV. - 1521-6942. ; 34:5
-
Journal article (other academic/artistic)abstract
- Musculoskeletal health is critical for human function, enabling mobility, dexterity and the ability to work and actively participate in all aspects of life. It is essential for maintaining economic, social and functional independence as well as human capital across the life course. Action is needed and the Global Alliance for Musculoskeletal Health (G-MUSC) is working with the entire musculoskeletal community to develop a global consensus on the important components of a global strategy. This will serve to influence and accelerate the priorities and actions of countries and international agencies such as the WHO. This issue aims to provide a background for developing such a global strategy for improving musculoskeletal health.
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