| 21. |
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| 22. |
- Buttazzoni, Christian, et al.
(författare)
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Does a childhood fracture predict low bone mass in young adulthood? - A 27-year prospective controlled study.
- 2013
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Ingår i: Journal of Bone and Mineral Research. - : Wiley. - 1523-4681 .- 0884-0431. ; 28:2, s. 351-359
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: A fracture in childhood is associated with low bone mineral density (BMD), but it is debated whether a fracture at growth also predicts low BMD in young adulthood. PURPOSE: To gender-specifically evaluate whether children with a fracture are at increased risk of low BMD in young adulthood. METHODS: Distal forearm BMD (g/cm(2) ) was measured with single photon absorptiometry (SPA) in 47 boys and 26 girls (mean age 10 years, range 3-16) with an index fracture and in 41 boys and 43 girls (mean age 10 years, range 4-16) with no fracture. BMD was re-measured mean 27 years later with the same SPA apparatus and with dual energy absorptiometry (DXA), quantitative ultrasound (QUS) and peripheral computed tomography (pQCT). Individual Z-scores were calculated using the control cohort as reference population. Data are presented as means with 95% confidence intervals (95% CI) within brackets and correlation with Pearson's correlation coefficient RESULTS: Boys with an index fracture had at fracture event a distal forearm BMD Z-score of -0.4 (-0.7, -0.1) and at follow-up -0.4 (-0.7, -0.1). Corresponding values in girls were -0.2 (-0.5, 0.1) and -0.3 (-0.7, 0.1). The deficit in absolute bone mass was driven by men with index fractures in childhood due to low rather than moderate or high energy. There were no changes in BMD Z-score during the follow-up period. The BMD deficit at follow-up was in boys with an index fracture verified with all advocated techniques CONCLUSIONS: A childhood fracture in men was associated with low BMD and smaller bone size in young adulthood while the deficit in women did not reach statistical significance. © 2012 American Society for Bone and Mineral Research.
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| 23. |
- Byberg, Liisa, et al.
(författare)
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Birth Weight is not Associated with Risk of Fracture : Results From Two Swedish Cohort Studies
- 2014
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Ingår i: Journal of Bone and Mineral Research. - : Wiley. - 0884-0431 .- 1523-4681. ; 29:10, s. 2152-2160
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Tidskriftsartikel (refereegranskat)abstract
- Development and growth in utero has been suggested to influence bone health. However, the relationship with risk of fracture in old age is largely unknown. Using Cox proportional hazards regression, we studied the association between birth weight and fractures at ages 50-94 among 10,893 men and women (48% women) from the Uppsala Birth Cohort Study (UBCoS, born 1915-29) and 1,334 men from the Uppsala Longitudinal Study of Adult Men (ULSAM, born 1920-24). Measured birth weight was collected from hospital or midwives' records and fractures from the Swedish National Patient Register. We observed 2,796 fractures (717 of these were hip fractures) in UBCoS and 335 fractures (102 hip fractures) in ULSAM. In UBCoS, the hazard ratio (HR) per 1 kg increase in birth weight, adjusted for sex and socioeconomic status at birth, was 1.01 (95% confidence interval [CI], 0.94-1.09) for any fracture and 1.06 (95% CI, 0.91-1.23) for hip fracture. Estimates in ULSAM were similar. We did not observe a differential association of birth weight with fractures occurring before age 70 or after age 70 years. Neither birth weight standardized for gestational age nor gestational duration was associated with fracture rate. In linear regression, birth weight was not associated with bone mineral density among 303 82-year-old men in ULSAM but showed positive associations with total body bone mineral content (β per kg increase in birth weight, adjusted for social class and age, 133; 95% CI, 30-227). This association was attenuated after further adjustment for body mass index and height (β, 41; 95% CI, -43 to 126). We conclude that birth weight is associated with bone mineral content but this association does not translate into an association with risk of fracture in men and women aged 50-94 years.
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| 24. |
- Byberg, Liisa, et al.
(författare)
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Fruit and vegetable intake and risk of hip fracture : A cohort study of Swedish men and women
- 2015
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Ingår i: Journal of Bone and Mineral Research. - : Wiley. - 0884-0431 .- 1523-4681. ; 30:6, s. 976-984
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Tidskriftsartikel (refereegranskat)abstract
- Dietary guidelines recommend a daily intake of five servings of fruit and vegetables. Whether such intakes are associated with a lower risk of hip fracture is at present unclear. The aim of the present study was to investigate the dose-response association between habitual fruit and vegetable intake and hip fracture in a cohort study based on 40,644 men from the Cohort of Swedish Men (COSM) and 34,947 women from the Swedish Mammography Cohort (SMC) (total n=75,591), free from cardiovascular disease and cancer, who answered lifestyle questionnaires in 1997 (age 45-83 years). Intake of fruit and vegetables (servings/day) was assessed by food frequency questionnaire and incident hip fractures were retrieved from the Swedish Patient Register (1998-2010). The mean follow-up time was 14.2 years. One third of the participants reported an intake of fruit and vegetables of >5 servings/day, one third >3 to ≤5 servings/day, 28% >1 to ≤3 servings/day, and 6% reported ≤1 serving/day. During 1,037,645 person-years we observed 3,644 hip fractures (2,266, 62%, in women). The doseresponse association was found to be strongly non-linear (P<0.001). Men and women with zero consumption had 88% higher rate of hip fracture compared with those consuming 5 servings/day; adjusted hazard ratio (HR), 1.88 (95% CI, 1.53-2.32). The rate was gradually lower with higher intakes; adjusted HR for 1 vs 5 servings/day, 1.35 (95% CI, 1.21-1.58). However, more than 5 servings/day did not confer additionally lower HRs (adjusted HR for 8 vs. 5 servings/day, 0.96 (95% CI, 0.90-1.03). Similar results were observed when men and women were analyzed separately. We conclude that there is a dose-response association between fruit and vegetable intake and hip fracture such that an intake below the recommended 5 servings/day confers higher rates of hip fracture. Intakes above this recommendation do not seem to further lower the risk.
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| 25. |
- Byberg, Liisa, et al.
(författare)
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Mediterranean Diet and Hip Fracture in Swedish Men and Women.
- 2016
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Ingår i: Journal of Bone and Mineral Research. - : Wiley. - 0884-0431 .- 1523-4681. ; 31:12, s. 2098-2105
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Tidskriftsartikel (refereegranskat)abstract
- A Mediterranean diet, known to have beneficial effects on cardiovascular health, may also influence the risk of hip fracture although previous studies present discrepant results. We therefore aimed to determine whether the rate of hip fracture was associated with degree of adherence to a Mediterranean diet. We combined two Swedish cohort studies consisting of 37,903 men and 33,403 women (total n = 71,333, mean age 60 years) free of previous cardiovascular disease and cancer who answered a medical and a food-frequency questionnaire in 1997. A modified Mediterranean diet score (mMED; range, 0 to 8 points) was created based on high consumption of fruits and vegetables, legumes and nuts, whole grains, fermented dairy products, fish, and olive/rapeseed oil, moderate intake of alcohol, and low intake of red and processed meat. Incident hip fractures between January 1, 1998, and December 31, 2012, were retrieved from the National Patient Register. Hazard ratios (HRs) and 95% confidence intervals (CIs) adjusted for potential confounders were calculated using Cox proportional hazards regression. Differences in age at hip fracture were calculated using multivariable Laplace regression. During follow-up, 3175 hip fractures occurred at a median age of 73.3 years. One unit increase in the mMED was associated with 6% lower hip fracture rate (adjusted HR = 0.94; 95% CI, 0.92 to 0.96) and with a 3-month higher median age at hip fracture (50th percentile difference = 2.8 months; 95% CI, 1.4 to 4.2). Comparing the highest quintile of adherence to the mMED (6 to 8 points) with the lowest (0 to 2 points) conferred an adjusted HR of hip fracture of 0.78 (95% CI, 0.69 to 0.89) and a 12-month higher median age of hip fracture (50th percentile difference = 11.6 months; 95% CI, 4.2 to 19.0). Results were similar in men and women. We conclude that higher adherence to a Mediterranean-like diet is associated with lower risk of future hip fracture.
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| 26. |
- Byberg, Liisa, et al.
(författare)
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Prediction of fracture risk in men : A cohort study
- 2012
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Ingår i: Journal of Bone and Mineral Research. - : Wiley. - 0884-0431 .- 1523-4681. ; 27:4, s. 797-807
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Tidskriftsartikel (refereegranskat)abstract
- FRAX is a tool that identifies individuals with high fracture risk who will benefit from pharmacological treatment of osteoporosis. However, a majority of fractures among elderly occur in people without osteoporosis and most occur after a fall. Our aim was to accurately identify men with a high future risk of fracture, independent of cause. In the population-based Uppsala Longitudinal Study of Adult Men (ULSAM) and using survival analysis we studied different models' prognostic values (R(2) ) for any fracture and hip fracture within 10 years from age 50 (n = 2322), 60 (n = 1852), 71 (n = 1221), and 82 (n = 526). During the total follow-up period from age 50, 897 fractures occurred in 585 individuals. Of these, 281 were hip fractures occurring in 189 individuals. The rates of any fracture were 5.7/1000 person-years at risk from age 50 and 25.9/1000 person-years at risk from age 82. Corresponding hip fractures rates were 2.9 and 11.7/1000 person-years at risk. The FRAX model included all variables in FRAX except bone mineral density. The full model combining FRAX variables, comorbidity, medications, and behavioral factors explained 25-45% of all fractures and 80-92% of hip fractures, depending on age. The corresponding prognostic values of the FRAX model were 7-17% for all fractures and 41-60% for hip fractures. Net reclassification improvement (NRI) comparing the full model with the FRAX model ranged between 40 and 53% for any fracture and between 40 and 87% for hip fracture. Within the highest quintile of predicted fracture risk with the full model, 1/3 of the men will have a fracture within 10 years after age 71 years and 2/3 after age 82 years. We conclude that the addition of comorbidity, medication and behavioral factors to the clinical components of FRAX can substantially improve the ability to identify men at high risk of fracture, especially hip fracture.
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| 27. |
- Börjesson, Anna E, et al.
(författare)
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The role of activation functions 1 and 2 of estrogen receptor-alpha for the effects of estradiol and selective estrogen receptor modulators in male mice
- 2013
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Ingår i: Journal of Bone and Mineral Research. - : Wiley. - 0884-0431 .- 1523-4681. ; 28:5, s. 1117-1126
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Tidskriftsartikel (refereegranskat)abstract
- Estradiol (E2) is important for male skeletal health and the effect of E2 is mediated via estrogen receptor (ER)-. This was demonstrated by the findings that men with an inactivating mutation in aromatase or a nonfunctional ER had osteopenia and continued longitudinal growth after sexual maturation. The aim of the present study was to evaluate the role of different domains of ER for the effects of E2 and selective estrogen receptor modulators (SERMs) on bone mass in males. Three mouse models lacking either ERAF-1 (ERAF-10), ERAF-2 (ERAF-20), or the total ER (ER/) were orchidectomized (orx) and treated with E2 or placebo. E2 treatment increased the trabecular and cortical bone mass and bone strength, whereas it reduced the thymus weight and bone marrow cellularity in orx wild type (WT) mice. These parameters did not respond to E2 treatment in orx ER/ or ERAF-20 mirx ERAF-10 mice were tissue-dependent, with a clear response in cortical bone parameters and bone marrow cellularity, but no response in trabecular bone. To determine the role of ERAF-1 for the effects of SERMs, we treated orx WT and ERAF-10 mice with raloxifene (Ral), lasofoxifene (Las), bazedoxifene (Bza), or vehicle. These SERMs increased total body areal bone mineral density (BMD) and trabecular volumetric BMD to a similar extent in orx WT mice. Furthermore, only Las increased cortical thickness significantly and only Bza increased bone strength significantly. However, all SERMs showed a tendency toward increased cortical bone parameters. Importantly, all SERM effects were absent in the orx ERAF-10 mice. In conclusion, ERAF-2 is required for the estrogenic effects on all evaluated parameters, whereas the role of ERAF-1 is tissue-specific. All evaluated effects of Ral, Las and Bza are dependent on a functional ERAF-1. Our findings might contribute to the development of bone-specific SERMs in males. (c) 2013 American Society for Bone and Mineral Research.
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| 28. |
- Börjesson, Anna E, et al.
(författare)
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The role of estrogen receptor-alpha in growth plate cartilage for longitudinal bone growth.
- 2010
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Ingår i: Journal of bone and mineral research. - : Wiley. - 1523-4681 .- 0884-0431. ; 25:12, s. 2414-24
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Tidskriftsartikel (refereegranskat)abstract
- Estrogens enhance skeletal growth during early sexual maturation while high estradiol levels during late puberty result in growth plate fusion in humans. Although the growth plates do not fuse directly after sexual maturation in rodents, a reduction in growth plate height is seen by treatment with a high dose of estradiol. It is unknown whether the effects of estrogens on skeletal growth are mediated directly via estrogen receptors (ERs) in growth plate cartilage and/or indirectly via other mechanisms such as the GH/IGF-I axis. To determine the role of ERalpha in growth plate cartilage for skeletal growth, we developed a mouse model with cartilage-specific inactivation of ERalpha. Although mice with total ERalpha inactivation displayed affected longitudinal bone growth associated with alterations in the GH/IGF-I axis, the skeletal growth was normal during sexual maturation in mice with cartilage-specific ERalpha inactivation. High dose estradiol treatment of adult mice reduced the growth plate height as a consequence of attenuated proliferation of growth plate chondrocytes in control mice but not in cartilage-specific ERalpha(-/-) mice. Adult cartilage-specific ERalpha(-/-) mice continued to grow after four months of age while growth was limited in control mice, resulting in increased femur length in one-year-old cartilage-specific ERalpha(-/-) mice compared with control mice. We conclude that during early sexual maturation ERalpha in growth plate cartilage is not important for skeletal growth. In contrast, it is essential for high dose estradiol to reduce the growth plate height in adult mice and for reduction of longitudinal bone growth in elderly mice. (c) 2010 American Society for Bone and Mineral Research.
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| 29. |
- Capulli, Mattia, et al.
(författare)
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The C-Terminal Domain of Chondroadherin: A New Regulator of Osteoclast Motility Counteracting Bone Loss
- 2014
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Ingår i: Journal of Bone and Mineral Research. - : Wiley. - 1523-4681 .- 0884-0431. ; 29:8, s. 1833-1846
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Tidskriftsartikel (refereegranskat)abstract
- Chondroadherin (CHAD) is a leucine-rich protein promoting cell attachment through binding to integrin alpha(2)beta(1) and syndecans. We observed that CHAD mRNA and protein were lower in bone biopsies of 50-year-old to 65-year-old osteoporotic women and in bone samples of ovariectomized mice versus gender/age-matched controls, suggesting a role in bone metabolism. By the means of an internal cyclic peptide (cyclicCHAD), we observed that its integrin binding sequence impaired preosteoclast migration through a nitric oxide synthase 2-dependent mechanism, decreasing osteoclastogenesis and bone resorption in a concentration-dependent fashion, whereas it had no effect on osteoblasts. Consistently, cyclicCHAD reduced transcription of two nitric oxide downstream genes, migfilin and vasp, involved in cell motility. Furthermore, the nitric oxide donor, S-nitroso-N-acetyl-D, L-penicillamine, stimulated preosteoclast migration and prevented the inhibitory effect of cyclicCHAD. Conversely, the nitric oxide synthase 2 (NOS2) inhibitor, N5-(1-iminoethyl)-l-ornithine, decreased both preosteoclast migration and differentiation, confirming a role of the nitric oxide pathway in the mechanism of action triggered by cyclicCHAD. In vivo, administration of cyclicCHAD was well tolerated and increased bone volume in healthy mice, with no adverse effect. In ovariectomized mice cyclicCHAD improved bone mass by both a preventive and a curative treatment protocol, with an effect in line with that of the bisphosphonate alendronate, that was mimicked by the NOS2 inhibitor [L-N6-(1-Iminoethyl)-lysine. 2 dihydrochloride]. In both mouse models, cyclicCHAD reduced osteoclast and bone resorption without affecting osteoblast parameters and bone formation. In conclusion, CHAD is a novel regulator of bone metabolism that, through its integrin binding domain, inhibits preosteoclast motility and bone resorption, with a potential translational impact for the treatment of osteoporosis. (C) 2014 American Society for Bone and Mineral Research.
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| 30. |
- Chagin, A S, et al.
(författare)
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Estrogen receptor-beta inhibits skeletal growth and has the capacity to mediate growth plate fusion in female mice.
- 2004
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Ingår i: Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. - 0884-0431 .- 1523-4681. ; 19:1, s. 72-7
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Tidskriftsartikel (refereegranskat)abstract
- To determine the long-term role of ER beta in the regulation of longitudinal bone growth, appendicular and axial skeletal growth was followed and compared in female ER beta-/-, ER alpha-/-, and ER alpha-/- beta-/- mice. Our results show that ER beta inhibits appendicular and axial skeletal growth and has the capacity to induce fusion of the growth plates. INTRODUCTION: Estrogen affects skeletal growth and promotes growth plate fusion in humans. In rodents, the growth plates do not fuse after sexual maturation, but prolonged treatment with supraphysiological levels of estradiol has the capacity to fuse the growth plates. It should be emphasized that the estrogen receptor (ER) alpha-/- and the ER alpha-/- beta-/-, but not the ER beta-/-, mouse models have clearly increased serum levels of estradiol. MATERIALS AND METHODS: The skeletal growth was monitored by X-ray and dynamic histomorphometry, and the growth plates were analyzed by quantitative histology, calcein double labeling, bromodeoxyuridine (BrdU) incorporation, and TUNEL assay in 4- and 18-month-old female ER beta-/-, ER alpha-/-, and ER alpha-/- beta-/- mice. RESULTS: Young adult (4-month-old) ER beta-/- mice demonstrated an increased axial- and appendicular-skeletal growth, supporting the notion that ER beta inhibits skeletal growth in young adult female mice. Interestingly, the growth plates were consistently fused in the appendicular skeleton of 18-month-old female ER alpha-/- mice. This fusion of growth plates, caused by a prolonged exposure to supraphysiological levels of estradiol in female ER alpha-/- mice, must be mediated through ER beta because old ER alpah-/- beta-/- mice displayed unchanged, unfused growth plates. CONCLUSIONS: Our results confirm that ER beta is a physiological inhibitor of appendicular- and axial-skeletal growth in young adult female mice. Furthermore, we made the novel observation that ER beta, after prolonged supraphysiological estradiol exposure, has the capacity to mediate growth plate fusion in old female mice.
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