| 1. |
- Briggs, Andrew M., et al.
(författare)
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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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Ingår i: BMJ Global Health. - : BMJ. - 2059-7908. ; 6:6
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Tidskriftsartikel (refereegranskat)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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| 2. |
- Albaik, Mai, et al.
(författare)
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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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Ingår i: Archives of Osteoporosis. - : Springer Science and Business Media LLC. - 1862-3522 .- 1862-3514. ; 17:1
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Tidskriftsartikel (refereegranskat)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 S., et al.
(författare)
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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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Ingår i: Aging clinical and experimental research. - : Springer Science and Business Media LLC. - 1594-0667 .- 1720-8319. ; 32:11, s. 2241-2250
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Tidskriftsartikel (refereegranskat)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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| 4. |
- Ebrahimi, Parvaneh, et al.
(författare)
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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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Ingår i: Epigenetics. - : Informa UK Limited. - 1559-2294 .- 1559-2308. ; 16:1, s. 92-105
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Tidskriftsartikel (refereegranskat)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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| 5. |
- Ericsson, Ylva B., et al.
(författare)
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Knee pain in young adult women- associations with muscle strength, body composition and physical activity
- 2021
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Ingår i: BMC Musculoskeletal Disorders. - : Springer Science and Business Media LLC. - 1471-2474. ; 22:1
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Tidskriftsartikel (refereegranskat)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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| 6. |
- Ivaska, Kaisa K., et al.
(författare)
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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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Ingår i: Calcified Tissue International. - : Springer Science and Business Media LLC. - 0171-967X .- 1432-0827. ; 111:3, s. 288-299
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Tidskriftsartikel (refereegranskat)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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| 7. |
- Jensen, Vivi Fh, et al.
(författare)
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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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Ingår i: BMC Research Notes. - 1756-0500. ; 16:1
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Tidskriftsartikel (refereegranskat)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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| 8. |
- Jensen, Vivi F.H., et al.
(författare)
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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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Ingår i: Bone. - : Elsevier BV. - 8756-3282. ; 145
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Forskningsöversikt (refereegranskat)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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| 9. |
- Jensen, Vivi F.H., et al.
(författare)
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Inner histopathologic changes and disproportionate zone volumes in foetal growth plates following gestational hypoglycaemia in rats
- 2020
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1
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Tidskriftsartikel (refereegranskat)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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| 10. |
- Malmgren, Linnea, et al.
(författare)
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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
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 12:1
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Tidskriftsartikel (refereegranskat)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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