| 1. |
- Johansson, Helena, 1981, et al.
(författare)
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High serum adiponectin predicts incident fractures in elderly men: Osteoporotic fractures in men (MrOS) Sweden
- 2012
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Ingår i: Journal of Bone and Mineral Research. - : Wiley. - 1523-4681 .- 0884-0431. ; 27:6, s. 1390-1396
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Tidskriftsartikel (refereegranskat)abstract
- Adipocytes and osteoblasts share a common progenitor, and there is, therefore, potential for both autocrine and endocrine effects of adiponectin on skeletal metabolism. The aim of the present study was to determine whether high serum adiponectin was associated with an increased risk of fracture in elderly men. We studied the relationship between serum adiponectin and the risk of fracture in 999 elderly men drawn from the general population and recruited to the Osteoporotic Fractures in Men (MrOS) study in Gothenburg, Sweden. Baseline data included general health questionnaires, lifestyle questionnaires, body mass index (BMI), bone mineral density (BMD), serum adiponectin, osteocalcin, and leptin. Men were followed for up to 7.4 years (average, 5.2 years). Poisson regression was used to investigate the relationship between serum adiponectin, other risk variables and the time-to-event hazard function of fracture. Median levels of serum adiponectin at baseline were 10.4 mu g/mL (interquartile range, 7.714.3). During follow-up, 150 men sustained one or more fractures. The risk of fracture increased in parallel with increasing serum adiponectin (hazard ratio [HR]/SD, 1.46; 95% confidence interval [CI], 1.231.72) and persisted after multivariate-adjusted analysis (HR/SD, 1.30; 95% CI, 1.091.55). Serum adiponectin shows graded stepwise association with a significant excess risk of fracture in elderly men that was independent of several other risk factors for fracture. Its measurement holds promise as a risk factor for fracture in men. (C) 2012 American Society for Bone and Mineral Research.
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| 2. |
- Kristjansdottir, Hallgerdur Lind, et al.
(författare)
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Anemia is associated with increased risk of non-vertebral osteoporotic fractures in elderly men: the MrOS Sweden cohort
- 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
- This study includes 1005 men from the Gothenburg part of the Osteoporotic Fracture in Men Study (MrOS). Included are 66 men with anemia (hemoglobin < 130 g/L). The follow-up time was up to 16 years, and the main results are that anemia is associated with all fractures and non-vertebral osteoporotic fractures. Introduction Anemia and osteoporotic fractures are conditions that are associated with increased morbidity and mortality. Clinical studies have suggested that anemia can be used as a predictor of future osteoporotic fractures. Method Men from the Osteoporotic Fractures in Men Study (MrOS) Sweden, Gothenburg, with available hemoglobin (Hb) values (n = 1005, median age 75.3 years (SD 3.2)), were included in the current analyses. Of these, 66 suffered from anemia, defined as Hb < 130 g/L. Median follow-up time for fracture was 10.1 years and the longest follow-up time was 16.1 years. Results Men with anemia had, at baseline, experienced more falls and had a higher prevalence of diabetes, cancer, prostate cancer, hypertension, and stroke. Anemia was not statistically significantly associated with bone mineral density (BMD). Men with anemia had higher serum levels of fibroblast growth factor 23 (iFGF23) (p < 0.001) and phosphate (p = 0.001) and lower serum levels of testosterone (p < 0.001) and estradiol (p < 0.001). Moreover, men with anemia had an increased risk of any fracture (hazard ratio (HR) 1.97, 95% CI 1.28-3.02) and non-vertebral osteoporotic fracture (HR 2.15, 95% CI 1.18-3.93), after adjustment for age and total hip BMD, in 10 years. The risk for any fracture was increased in 10 and 16 years independently of falls, comorbidities, inflammation, and sex hormones. The age-adjusted risk of hip fracture was increased in men with anemia (HR 2.32, 95% CI 1.06-5.12), in 10 years, although this was no longer statistically significant after further adjustment for total hip BMD. Conclusions Anemia is associated with an increased risk for any fracture and non-vertebral osteoporotic fracture in elderly men with a long follow-up time. The cause is probably multifactorial and our results support that anemia can be used as a predictor for future fracture.
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| 3. |
- Kristjansdottir, Hallgerdur Lind, et al.
(författare)
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High Plasma Erythropoietin Predicts Incident Fractures in Elderly Men with Normal Renal Function : The MrOS Sweden Cohort
- 2020
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Ingår i: Journal of Bone and Mineral Research. - : WILEY. - 0884-0431 .- 1523-4681. ; 35:2, s. 298-305
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Tidskriftsartikel (refereegranskat)abstract
- Preclinical studies on the role of erythropoietin (EPO) in bone metabolism are contradictory. Regeneration models indicate an anabolic effect on bone healing, whereas models on physiologic bone remodeling indicate a catabolic effect on bone mass. No human studies on EPO and fracture risk are available. It is known that fibroblast growth factor 23 (FGF23) affects bone mineralization and that serum concentration of FGF23 is higher in men with decreased estimated glomerular filtration rate (eGFR). Recently, a direct association between EPO and FGF23 has been shown. We have explored the potential association between EPO and bone mineral density (BMD), fracture risk, and FGF23 in humans. Plasma levels of EPO were analyzed in 999 men (aged 69 to 81 years), participating in the Gothenburg part of the population-based Osteoporotic Fractures in Men (MrOS) study, MrOS Sweden. The mean +/- SD EPO was 11.5 +/- 9.0 IU/L. Results were stratified by eGFR 60 mL/min. For men with eGFR >= 60 mL/min (n = 728), EPO was associated with age (r = 0.13, p < 0.001), total hip BMD (r = 0.14, p < 0.001), intact (i)FGF23 (r = 0.11, p = 0.004), and osteocalcin (r = -0.09, p = 0.022). The association between total hip BMD and EPO was independent of age, body mass index (BMI), iFGF23, and hemoglobin (beta = 0.019, p < 0.001). During the 10-year follow-up, 164 men had an X-ray-verified fracture, including 117 major osteoporotic fractures (MOF), 39 hip fractures, and 64 vertebral fractures. High EPO was associated with higher risk for incident fractures (hazard ratio [HR] = 1.43 per tertile EPO, 95% confidence interval [CI] 1.35-1.63), MOF (HR = 1.40 per tertile EPO, 95% CI 1.08-1.82), and vertebral fractures (HR = 1.42 per tertile EPO, 95% CI 1.00-2.01) in a fully adjusted Cox regression model. In men with eGFR<60 mL/min, no association was found between EPO and BMD or fracture risk. We here demonstrate that high levels of EPO are associated with increased fracture risk and increased BMD in elderly men with normal renal function.
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| 4. |
- Kristjansdottir, Hallgerdur Lind, et al.
(författare)
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High platelet count is associated with low bone mineral density: The MrOS Sweden cohort.
- 2021
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Ingår i: Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA. - : Springer Science and Business Media LLC. - 1433-2965 .- 0937-941X. ; 32:5, s. 865-871
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Tidskriftsartikel (refereegranskat)abstract
- In elderly ambulatory men, high platelet and high neutrophil counts are related to low bone mineral density (BMD), after adjustment for relevant covariates. Low hemoglobin (hgb) is even associated with low BMD, but this relationship seems to be dependent on estradiol and osteocalcin.Blood and bone cells exist in close proximity to each other in the bone marrow. Accumulating evidence, from both preclinical and clinical studies, indicates that these cell types are interconnected. Our hypothesis was that BMD measurements are associated with blood count variables and bone remodeling markers.We analyzed blood count variables, bone remodeling markers, and BMD, in subjects from the MrOS cohort from Gothenburg, Sweden. Men with at least one blood count variable (hgb, white blood cell count, or platelet count) analyzed were included in the current analysis (n=1005), median age 75.3years (range 69-81years).Our results show that high platelet counts were related to low BMD at all sites (total hip BMD; r=-0.11, P=0.003). No statistically significant association was seen between platelet counts and bone remodeling markers. Neutrophil counts were negatively associated with total body BMD (r=-0.09, P=0.006) and total hip BMD (r=-0.08, P=0.010), and positively related to serum ALP (r=0.15, P<0.001). Hgb was positively related to total hip BMD (r=0.16, P<0.001), and negatively to serum osteocalcin (r=-0.13, P<0.001). The association between platelet and neutrophil counts and total hip BMD was statistically significant after adjustments for other covariates, but the association between hgb and total hip BMD was dependent on estradiol and osteocalcin.Our observations support the hypothesis of an interplay between blood and bone components.
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| 5. |
- Kristjansdottir, Hallgerdur Lind, et al.
(författare)
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High Serum Serotonin Predicts Increased Risk for Hip Fracture and Nonvertebral Osteoporotic Fractures : The MrOS Sweden Study
- 2018
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Ingår i: Journal of Bone and Mineral Research. - : Wiley. - 0884-0431. ; 33:9, s. 1560-1567
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Tidskriftsartikel (refereegranskat)abstract
- Because several studies have implicated serotonin as a regulator of bone mass, we here explore its potential association on fracture risk and falls, as on bone mineral density (BMD) and muscle strength, in humans. Serum levels of serotonin were analyzed in 950 men (aged 69 to 81 years), participating in the Gothenburg part of the population-based study MrOS Sweden. Men taking selective serotonin reuptake inhibitors (SSRIs) had a mean value of 31.2 μg/L compared with 159.4 μg/L in those not taking SSRIs. SSRI users were excluded from further analysis. During 10-year follow-up, 224 men exhibited fractures, including 97 nonvertebral osteoporotic fractures (57 hip fractures), and 86 vertebral fractures. Serotonin was associated with hip fracture in linear analysis (hazard ratio [HR] = 1.27, 95% confidence interval [CI] 1.03–1.58) and to all fractures in a nonlinear manner, when quintiles of serotonin was included in quadratic terms (HR = 1.12, 95% CI 1.04–1.21). Men in serotonin quintile 5 had, in multivariable analysis, a HR of 2.30 (95% CI 1.31–4.02) for hip fracture and 1.82 (95% CI 1.17–2.85) for nonvertebral fractures compared with men in quintiles 1 to 4. Men in quintile 1 had, in multivariable analysis, a HR of 1.76 (95% CI 1.03–2.99) for nonvertebral fractures compared with men in quintiles 2 to 4. No association was found with vertebral fractures. Individuals in serotonin quintile 1 had higher prevalence of falls compared with quintiles 2 to 5 (odds ratio = 1.90, 95% CI 1.26–2.87). Serotonin was positively associated with hand-grip strength (r = 0.08, p = 0.02) and inversely with hip BMD (r = −0.10, p = 0.003). To assess the association between SSRIs and falls and fractures, the total MrOS Sweden cohort was examined (n = 3014). SSRI users (n = 90) had increased prevalence of falls (16% versus 33%, p = 0.0001) and increased rate of incident fractures (28.0 versus 44.7 per 1000 person-years, p = 0.018). We present novel data showing that high levels of serotonin predict an increased risk for hip fracture and nonvertebral osteoporotic fractures.
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| 6. |
- Lewerin, Catharina, 1961, et al.
(författare)
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High plasma osteocalcin is associated with low blood haemoglobin in elderly men: the MrOS Sweden Study
- 2016
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Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 280:4, s. 398-406
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: It has been suggested that osteoblasts are involved in the regulation of haematopoietic stem cells. Whether osteocalcin, which is derived from osteoblasts and is metabolically active, influences blood haemoglobin (Hb) levels is not known. OBJECTIVE: To determine whether plasma osteocalcin is a determinant of Hb in elderly men. METHODS: A total of 993 men (mean age 75.3 +/- 3.2 years) participated in the population-based MrOS (osteoporotic fractures in men) study. Plasma osteocalcin concentration was evaluated in relation to Hb and adjustments were made for potential confounders (i.e. age, body mass index, erythropoietin, total oestradiol, fasting insulin, adiponectin, ferritin and cystatin C). RESULTS: Hb correlated (age adjusted) negatively with osteocalcin in the total study group (r = -0.12, P < 0.001) as well as in the subgroup of nondiabetic men (r = -0.16, P < 0.001). In nondiabetic men with higher osteocalcin levels, it was more likely that Hb would be in the lowest quartile (odds ratio per SD decrease in osteocalcin 1.32, 95% confidence interval 1.13-1.53). Quartiles of Hb were negatively associated (age adjusted) with osteocalcin (P < 0.001). Anaemic men (47/812) (Hb <130 g L-1 ) had significantly higher mean osteocalcin levels than nonanaemic men (33.9 vs. 27.1 mug L-1 , P < 0.001). In multiple stepwise linear regression analyses (adjusted for age, body mass index, total oestradiol, adiponectin, erythropoietin, fasting insulin, cystatin C, leptin, ferritin and holotranscobalamin), osteocalcin was an independent predictor of Hb concentration in nondiabetic men (P < 0.05). CONCLUSIONS: These data add further support to the evidence indicating that the bone-specific protein osteocalcin has several endocrine functions targeting the pancreas, testes, adipocytes, brain. An additional novel finding is that osteocalcin may also have a paracrine function as a regulator of haematopoiesis.
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| 7. |
- Lewerin, Catharina, 1961, et al.
(författare)
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High serum adiponectin is associated with low blood haemoglobin in elderly men: the Swedish MrOS study
- 2015
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Ingår i: Journal of Internal Medicine. - : Wiley. - 1365-2796 .- 0954-6820. ; 278:1, s. 68-76
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Blood haemoglobin (Hb) concentration declines in elderly men, whilst the level of the adipocyte-derived protein adiponectin increases with age. The association between erythropoiesis and adiponectin in elderly men is unclear. The aim of this study was to determine whether adipokines such as adiponectin and leptin are associated with anaemia and Hb concentration in elderly community-dwelling men. Design and setting: The Gothenburg part of the population-based Swedish Osteoporotic Fractures in Men (MrOS) cohort (n=1010; median age 75.3years, range 69-81). Main outcome measures: We investigated the associations between levels of adiponectin and Hb before and after adjusting for potential confounders [i.e. age, body composition, erythropoietin (EPO), total oestradiol, leptin, cystatin C and iron and B vitamin status]. Results: In these elderly men, age was negatively associated with Hb (r=-0.12, P<0.001) and positively associated with adiponectin level (r=0.13, P<0.001). In age-adjusted partial correlations, Hb and adiponectin levels were negatively correlated (r=-0.20, P<0.001); this association remained significant after multivariable adjustment for age, body composition, EPO, fasting insulin, sex hormones, leptin and ferritin. Age-adjusted mean adiponectin concentrations were significantly higher in anaemic men (66/1005; Hb <130gL(-1)) compared to nonanaemic men (14.0 vs. 11.7 gmL(-1), P<0.05). In multivariate analysis, adiponectin together with EPO, total oestradiol, insulin, albumin, transferrin saturation, HDL cholesterol, cystatin C, total body fat mass and free thyroxine, but not leptin, explained 35% of the variation in Hb level. These results remained essentially unchanged after exclusion of men with diabetes. Conclusions: Serum adiponectin, but not leptin, was negatively and independently associated with Hb. This finding suggests a possible role of adiponectin in the age-related decline in Hb level observed in apparently healthy elderly men.
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| 8. |
- Lewerin, Catharina, 1961, et al.
(författare)
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Low holotranscobalamin and cobalamins predict incident fractures in elderly men: the MrOS Sweden.
- 2014
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Ingår i: Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA. - : Springer Science and Business Media LLC. - 1433-2965 .- 0937-941X. ; 25:1, s. 131-140
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Tidskriftsartikel (refereegranskat)abstract
- In a population-based study on cobalamin status and incident fractures in elderly men (n=790) with an average follow-up of 5.9years, we found that low levels of metabolically active and total cobalamins predict incident fractures, independently of body mass index (BMI), bone mineral density (BMD), plasma total homocysteine (tHcy), and cystatin C.
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| 9. |
- Nilsson, Karin H., et al.
(författare)
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RSPO3 is important for trabecular bone and fracture risk in mice and humans
- 2021
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Genetic association signals for fractures have been reported at the RSPO3 locus, but the causal gene and the underlying mechanism are unknown. Here, the authors show that RSPO3 exerts an important role for vertebral trabecular bone mass and bone strength in mice and fracture risk in humans. With increasing age of the population, countries across the globe are facing a substantial increase in osteoporotic fractures. Genetic association signals for fractures have been reported at the RSPO3 locus, but the causal gene and the underlying mechanism are unknown. Here we show that the fracture reducing allele at the RSPO3 locus associate with increased RSPO3 expression both at the mRNA and protein levels, increased trabecular bone mineral density and reduced risk mainly of distal forearm fractures in humans. We also demonstrate that RSPO3 is expressed in osteoprogenitor cells and osteoblasts and that osteoblast-derived RSPO3 is the principal source of RSPO3 in bone and an important regulator of vertebral trabecular bone mass and bone strength in adult mice. Mechanistic studies revealed that RSPO3 in a cell-autonomous manner increases osteoblast proliferation and differentiation. In conclusion, RSPO3 regulates vertebral trabecular bone mass and bone strength in mice and fracture risk in humans.
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| 10. |
- Nordström, Anna, 1973-, et al.
(författare)
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Interleukin-6 promoter polymorphism is associated with bone quality assessed by calcaneus ultrasound and previous fractures in a cohort of 75-year-old women.
- 2004
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Ingår i: Osteoporosis international. - : Springer Science and Business Media LLC. - 0937-941X .- 1433-2965. ; 15:10, s. 820-6
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Tidskriftsartikel (refereegranskat)abstract
- Interleukin 6 (IL-6) is a multifunctional cytokine and a potent stimulator of bone resorption and has been implicated in the pathogenesis of osteoporosis in postmenopausal women. The aim of this study was to investigate if a functional IL-6 promoter polymorphism (-174) was related to bone mass and fractures in a cohort consisting of 964 postmenopausal Caucasian women aged 75 years. Bone mineral density (BMD; g/cm2) of the femoral neck, lumbar spine and total body was measured using dual energy X-ray absorptiometry (DXA). Quantitative ultrasound (QUS) was also measured in the calcaneus and quantified as speed of sound (SOS; m/s), broadband ultrasound attenuation (BUA; dB/MHz), and stiffness index (SI). IL-6 genotypes was determined by restriction fragment length polymorphism (RFLP) using the restriction enzyme NlaIII. The frequencies of the different IL-6 genotypes were 27.5% (GG), 47.9% (GC), 24.6% (CC). The IL-6 polymorphism (presence of G) was independently related to a lower stiffness (beta=-0.07; P=0.03) and BUA (beta=-0.08; P=0.02), but not to BMD at any site measured by DXA. In the cohort, 420 subjects (44%) reported at least one fracture during their lifetime, and 349 (36%) reported at least one fracture after the age of 50. Using binary logistic regression, the IL-6 polymorphism (presence of G) was significantly related to an increased risk of a previous fracture during life (odds ratio 1.46, 95% CI 1.08-1.97) and to an increased risk of a fracture occurring after 50 years of age (odds ratio 1.37, 95% CI 1.004-1.88). The risk was further increased for fractures grouped as osteoporotic fractures (odds ratio 1.67, 95% CI 1.14-2.45), including forearm fractures (odds ratio 1.59, 95% CI 1.05-2.40). In conclusion, presence of G allele in the IL-6 promoter polymorphism at position -174 is independently related to previous fractures in postmenopausal women. This association may be related primarily to an altered bone quality identified by QUS and not a lower bone mass. This is also the first demonstration of association of IL-6 gene polymorphism to calcaneal QUS.
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