| 1. |
- Bergström, Ulrica, 1970-
(författare)
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Fragility fractures in fragile people : epidemiology of the age quake
- 2009
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Osteoporosis-related fracture is already today a major public health problem and the number of hip fractures is expected to double to 2030. Sweden has one of the highest hip fracture incidences worldwide. This may be explained by several factors: e.g. age, genetic, climatologic, geographic and a relative vitamin D deficiency, secondary to the limited sunlight exposure especially during winter months. Intrinsic and extrinsic factors contribute to a fracture, although a prior low energy fracture is one of the strongest predictors for a subsequent one and this should be a target for secondary fracture prevention in an orthopaedic setting. Since 1993 all injured patients admitted to the emergency floor and all in-hospital fractures at Umeå University Hospital, Sweden, were registered according to the Injury Data Base, former EHLASS. There were 31,173 fracture events (one or more fractures at the same time), of which 13,931 were in patients’ ≥ 50 years old. The fracture database was co analyzed with the Northern Sweden Health and Disease Study cohort in a nested case-control study for investigations of associations between osteoporotic fracture and serum markers, lifestyle data, nutrition etc. We found that there were differences in fracture pattern depending on age and sex. Both injury mechanism and fracture site were strongly dependent of age. The most severe fragility fracture, hip fracture, had a decreasing incidence. However, the incidence curve was right-shifting leading to an increase, both in numbers and in incidence of hip fractures among the oldest female. To identify people at high risk for fractures, re-fracture patients are useful. No less than 21% of the fracture patients had suffered more than one fracture event, accounting for 38% of all fracture events. The total risk ratio for a subsequent fracture was 2.2 (2.1-2.3 95% CI). In males the highest risk for re fracture was in the age cohort 70-79 years (RR 2.7, 2.3-3.2 95% CI), in females > 90 years (RR 3.9, 3.2-4.8 95% CI). Another possible risk factor in this subarctic population is the lack of sunlight, leading to a vitamin D deficit. The overall adjusted risk of sustaining a hip fracture in this population was 2.7 (95%CI:1.3-5.4) in subjects with a serum 25 hydroxyvitamin D below 50 nmol/l. The association was, however, different according to age at baseline. Thus in subjects aged 60 years and above at baseline, the adjusted odds ratio of sustaining a hip fracture was 6.2 (1.2-32.5 95%CI) for the group of individuals with a serum 25OHD below 50 nmol/l, whereas no significant association was found in the youngest age group. In the next 30 years the ongoing demographic changes will accelerate. The World War II baby boomers will cause an age quake. We can already see signs heralding a new fracture pattern: an increasing cohort of mobile but fragile elderly, with considerable co-morbidity is now at risk for fragility fractures. In fracture patients, clinical information is sufficient to pinpoint patients with a high risk for re-fractures. It is therefore clinically important to use the information provided by the fracture event. We suggest that trauma units and primary care units should screen for risk factors and inform patients about the treatment options, and to organize fracture liaison services. This seems to be especially cost-efficient for our oldest and frailest patients. Secondary prophylaxis and follow-up treatment after cardiovascular disorders are now a matter of course worldwide, but the screening for risk factors, in order to prevent a second fracture, is often neglected. This is one of the most important issues of fracture care in the future in order to improve general health.
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| 2. |
- Bergström, Ulrica, 1970-, et al.
(författare)
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The hip fracture incidence curve is shifting to the right : a forecast of the age-quake
- 2009
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Ingår i: Acta Orthopaedica. - : Medical Journals Sweden AB. - 1745-3674 .- 1745-3682. ; 80:5, s. 520-524
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Tidskriftsartikel (refereegranskat)abstract
- Background The number of hip fractures has doubled in the last 30–40 years in many countries. Age-adjusted incidence has been reported to be decreasing in Europe and North America, but is there a decreasing trend in all age groups? Patients and methods This population-based study included all hip-fracture patients over 50 years of age (a total of 2,919 individuals, 31% of whom were men) admitted to Umeå University Hospital, Sweden, from 1993 through 2005. Results The incidence of hip fracture declined between the periods 1993–1996 and 2001–2005: from 706 to 625 hip fractures per 105 women and from 390 to 317 hip fractures per 105 men. However, there was a 114% increase in the number of fractures in women aged 90 or older (12 and 25 hip fractures/year, respectively, in the two time periods). For the period 2001–05, women ≥ 90 years of age accounted for almost the same numbers of hip fractures as women aged 75–79 (27 fractures/year). The rate increased during this period, from 2,700 per 105 women to 3,900 per 105 women > 90 years. In men there were declining trends for both relative and absolute numbers. Interpretation Although age-adjusted incidence declined in the population > 50 years of age, absolute fracture rate and incidence increased in the very old. Women over 90 now have the same absolute number of hip fractures every year as women aged 75–79 years. There was a right-shift in hip fracture distribution towards the oldest old, probably due to an increased number of octo/nonagenarians, a new population of particularly frail old people that hardly existed earlier. Better health among septuagenarians may also have delayed the age at which fractures occurred. This changing pattern will strain orthopedic and geriatric resources even more.
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| 3. |
- Eriksson, Anna-Lena, 1971, et al.
(författare)
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[Preparing for the licence to prescribe in medical school - a questionnaire study on medical students professional confidence in the art of prescribing]. : Läkemedelsarbete behöver vara integrerat i klinisk utbildning - Att göra många läkemedelsgenomgångar ökar trygghet och reflektion över patientens behandling, visar enkätstudie.
- 2019
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Ingår i: Lakartidningen. - 1652-7518. ; 116
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Tidskriftsartikel (refereegranskat)abstract
- A prerequisite for rational use of medicines is adequate prescribing skills; drug treatment isa complex task requiring diagnostic competence combined with pharmacologic knowledge and patient communication skills.Acquiring professional confidence in the art of prescribing is essential during medical training.The results of this questionnaire study, conducted in four medical schools in Sweden after the course in internal medicine (252 respondents; response rate: 74%; median age: 24 years, 61% female), show that 45% and 62% were confident in performing medication reviews and writing medication summary reports, respectively, i.e. the basics of prescribing. The confidence increased by the number of reviews and reports performed, i.e. the extent of practice (correlation coefficients: 0.41 and 0.38, respectively, both p<0.0001), as did the extent of the students' reflection on important aspects of drug treatment such as adherence, adverse reactions, renal function, dosing, and drug interactions. In multivariate regression analyses, major predictors for confidence in performing medication reviews were extent of practice and extent of clinical supervision. The results suggest that these factors are keys to acquiring professional confidence in the art of prescribing.
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| 4. |
- Estrada, Karol, et al.
(författare)
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Genome-wide meta-analysis identifies 56 bone mineral density loci and reveals 14 loci associated with risk of fracture.
- 2012
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 44:5, s. 491-501
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Tidskriftsartikel (refereegranskat)abstract
- Bone mineral density (BMD) is the most widely used predictor of fracture risk. We performed the largest meta-analysis to date on lumbar spine and femoral neck BMD, including 17 genome-wide association studies and 32,961 individuals of European and east Asian ancestry. We tested the top BMD-associated markers for replication in 50,933 independent subjects and for association with risk of low-trauma fracture in 31,016 individuals with a history of fracture (cases) and 102,444 controls. We identified 56 loci (32 new) associated with BMD at genome-wide significance (P < 5 × 10(-8)). Several of these factors cluster within the RANK-RANKL-OPG, mesenchymal stem cell differentiation, endochondral ossification and Wnt signaling pathways. However, we also discovered loci that were localized to genes not known to have a role in bone biology. Fourteen BMD-associated loci were also associated with fracture risk (P < 5 × 10(-4), Bonferroni corrected), of which six reached P < 5 × 10(-8), including at 18p11.21 (FAM210A), 7q21.3 (SLC25A13), 11q13.2 (LRP5), 4q22.1 (MEPE), 2p16.2 (SPTBN1) and 10q21.1 (DKK1). These findings shed light on the genetic architecture and pathophysiological mechanisms underlying BMD variation and fracture susceptibility.
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| 5. |
- Grahnemo, Louise, et al.
(författare)
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Low Circulating Valine Associate With High Risk of Hip Fractures
- 2023
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Ingår i: Journal of Clinical Endocrinology & Metabolism. - : Oxford University Press. - 0021-972X .- 1945-7197. ; 108:11
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Tidskriftsartikel (refereegranskat)abstract
- Context Hip fractures constitute a major health concern. An adequate supply of amino acids is crucial to ensure optimal acquisition and remodeling of bone. Circulating amino acid levels have been proposed as markers of bone mineral density, but data on their ability to predict incident fractures are scarce. Objectives To investigate the associations between circulating amino acids and incident fractures. Methods We used UK Biobank (n = 111 257; 901 hip fracture cases) as a discovery cohort and the Umea Fracture and Osteoporosis (UFO) hip fracture study (hip fracture cases n = 2225; controls n = 2225) for replication. Associations with bone microstructure parameters were tested in a subsample of Osteoporotic Fractures in Men Sweden (n = 449). Results Circulating valine was robustly associated with hip fractures in the UK Biobank (HR per SD increase 0.79, 95% CI 0.73-0.84), and this finding was replicated in the UFO study (combined meta-analysis including 3126 incident hip fracture cases, odds ratio per SD increase 0.84, 95% CI 0.80-0.88). Detailed bone microstructure analyses showed that high circulating valine was associated with high cortical bone area and trabecular thickness. Conclusion Low circulating valine is a robust predictor of incident hip fractures. We propose that circulating valine may add information for hip fracture prediction. Future studies are warranted to determine whether low valine is causally associated with hip fractures.
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| 6. |
- Nethander, Maria, 1980, et al.
(författare)
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BMD-Related Genetic Risk Scores Predict Site-Specific Fractures as Well as Trabecular and Cortical Bone Microstructure
- 2020
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Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 105:4
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Tidskriftsartikel (refereegranskat)abstract
- CONTEXT: It is important to identify patients at highest risk of fractures. OBJECTIVE: To compare the separate and combined performances of bone-related genetic risk scores (GRSs) for prediction of forearm, hip and vertebral fractures separately, as well as of trabecular and cortical bone microstructure parameters separately. DESIGN, SETTING, AND PARTICIPANTS: Using 1103 single nucleotide polymorphisms (SNPs) independently associated with estimated bone mineral density of the heel (eBMD), we developed a weighted GRS for eBMD and determined its contribution to fracture prediction beyond 2 previously developed GRSs for femur neck BMD (49 SNPs) and lumbar spine BMD (48 SNPs). Associations between these GRSs and forearm (ncases = 1020; ncontrols = 2838), hip (ncases = 1123; ncontrols = 2630) and vertebral (ncases = 288; ncontrols = 1187) fractures were evaluated in 3 Swedish cohorts. Associations between the GRSs and trabecular and cortical bone microstructure parameters (n = 426) were evaluated in the MrOS Sweden cohort. RESULTS: We found that eBMDGRS was the only significant independent predictor of forearm and vertebral fractures while both FN-BMDGRS and eBMDGRS were significant independent predictors of hip fractures. The eBMDGRS was the major GRS contributing to prediction of trabecular bone microstructure parameters while both FN-BMDGRS and eBMDGRS contributed information for prediction of cortical bone microstructure parameters. CONCLUSIONS: The eBMDGRS independently predicts forearm and vertebral fractures while both FN-BMDGRS and eBMDGRS contribute independent information for prediction of hip fractures. We propose that eBMDGRS captures unique information about trabecular bone microstructure useful for prediction of forearm and vertebral fractures. These findings may facilitate personalized medicine to predict site-specific fractures as well as cortical and trabecular bone microstructure separately.
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| 7. |
- Pettersson, Ulrika, 1970-
(författare)
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Bone mass in the young athlete
- 1999
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Bone mass and bone size accumulate during childhood and adolescence and peak in the twenties. The obtained peak bone mass has been suggested to be a major determinant of bone mass even in the very elderly. Although, genetic factors are the main determinants, environmental and lifestyle factors also play a crucial role in modulating maximal bone mass. Assessing these lifestyle factors would be of great importance for the intervention strategies against osteoporosis. The first aim of this thesis was to compare the bone mass and bone size in male and female young adults on a high level of physical activity with males or females on a low level of physical activity. Furthermore, it also aimed to investigate the influence of pubertal maturity, menstrual disturbances, and different body constitutional factors on bone mass and size during adolescence and young adulthood. The female activity groups consisted of cross-county skiers, soccer players, and rope skippers. Compared to their age-matched inactive controls, all these athletic groups demonstrated a significantly higher bone mineral density (BMD) at those sites subjected to the sport-specific loading. Rope-skipping, a very high impact activity was associated with a higher bone size, preferentially in the lower extremity, suggesting an effect of weight-bearing activity also on bone geometry. The effect of menstrual disturbances was evaluated in a group of long-distance runners, where amenorrheic runners had significantly lower BMD in both trabecular and also cortical bone in the lower extremity compared to eumenorrheic runners, suggesting that weight-bearing activity cannot compensate for the shortfall of reduced estrogen levels. The male activity groups consisted of ice hockey players and badminton players. Compared to their age-matched controls, both athletic groups demonstrated a significantly higher BMD at those sites subjected to the sport-specific loading. Especially badminton was associated with a high BMD, suggesting that physical activity, including jumps in unusual directions has a great osteogenic potential. The main determinants of BMD in both male and females were, except for type of physical activity, activity, muscle strength, height, and different body constitutional factors. However, the relationships with muscle strength and body constitution were somewhat weaker in the athletic groups, especially in the males, indicating that impact forces may be of greater importance in regulating bone mass in highly trained athletes. Yet bone size was largely determined by parameters related to body size and less strongly to physical activity. In a prospective study on adolescent boys, the changes in bone mass during late puberty were mainly accounted for by growth and development, including height and pubertal maturation, and less to physical activity level. Thus, the osteogenic effect from physical activity seems to be of importance for bone mass achievement predominantly before late puberty.
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| 8. |
- Pettersson, Ulrika, et al.
(författare)
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Physical activity is the strongest predictor of calcaneal peak bone mass in young Swedish men
- 2010
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Ingår i: Osteoporosis International. - : Springer. - 0937-941X .- 1433-2965. ; 21:3, s. 447-455
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Tidskriftsartikel (refereegranskat)abstract
- In a highly representative sample of young adult Swedish men (n = 2,384), we demonstrate that physical activity during childhood and adolescence was the strongest predictor of calcaneal bone mineral density (BMD), and that peak bone mass was reached at this site at the age of 18 years.INTRODUCTION: The purpose of the present study was to determine if physical activity during growth is associated with peak calcaneal BMD in a large, highly representative cohort of young Swedish men.METHODS: In this study, 2,384 men, 18.3 +/- 0.3 (mean +/- SD) years old, were included from a population attending the mandatory tests for selection to compulsory military service in Sweden. BMD (g/cm(2)) of the calcaneus was measured using dual-energy X-ray absorptiometry. Training habits were investigated using a standardized questionnaire.RESULTS: Regression analysis (with age, height, weight, smoking, and calcium intake as covariates) demonstrated that history of regular physical activity was the strongest predictor and could explain 10.1% of the variation in BMD (standardized beta = 0.31, p < 0.001). A regression model with quadratic age effect revealed maximum BMD at 18.4 years.CONCLUSIONS: We found that history of physical activity during growth was the strongest predictor of peak calcaneal BMD in young men.
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| 9. |
- Ramnemark, Anna, et al.
(författare)
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Adequate vitamin D levels in a Swedish population living above latitude 63°N : The 2009 Northern Sweden MONICA study
- 2015
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Ingår i: International Journal of Circumpolar Health. - : CoAction Publishing. - 1239-9736 .- 2242-3982. ; 74:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Even though vitamin D is mainly produced by exposure to sunlight, little is known regarding vitamin D levels in populations living in sub-Arctic areas with little or no daylight during winter.OBJECTIVE: We describe distributions of vitamin D3 and the prevalence of adequate levels in a population living above 63°N.DESIGN: We sampled 1,622 randomly selected subjects, aged 25-74 years, between January and May, 2009, as part of the Northern Sweden MONICA study (69.2% participation rate). By using HPLC, 25(OH) vitamin D3 was analysed. Levels used for definitions were deficient, D3<25 nmol/l (<10 ng/ml); insufficient, D3 25-49.9 nmol/l (10-20 ng/ml); and adequate, D3≥50 nmol/l (20 ng/ml).RESULTS: Mean (median) level of vitamin D3 was 65.2 (63.6) nmol/l in men and 71.0 (67.7) nmol/l in women. Adequate levels were found in 79.2%, more often in women (82.7%) than in men (75.6%). Only 0.7% of the population were vitamin D3-deficient but 23.1% of men and 17.1% of women had insufficient levels. Levels of vitamin D3 increased with age and insufficient status was most common among those aged 25-34 years, 41.0% in men and 22.3% in women. If subjects using vitamin D-supplementation are excluded, the population level of D3 is 1-2 nmol/l lower than in the general population across sex- and age groups. There were no differences between the northern or the southern parts, between urban or rural living or according to educational attainment. Those subjects born outside of Sweden or Finland had lower levels.CONCLUSION: The large majority living close to the Arctic Circle in Sweden have adequate D3 levels even during the second half of the dark winter. Subjects with D3 deficiency were uncommon but insufficient levels were often found among young men.
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| 10. |
- van Meurs, Joyce B, et al.
(författare)
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Large-scale analysis of association between LRP5 and LRP6 variants and osteoporosis.
- 2008
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Ingår i: JAMA : the journal of the American Medical Association. - Chicago : American Medical Association (AMA). - 1538-3598 .- 0098-7484. ; 299:11, s. 1277-90
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Tidskriftsartikel (refereegranskat)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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