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  • 1. Andersson, N.
    et al.
    Strandberg, L.
    Nilsson, S.
    Adamovic, S.
    Karlsson, M. K.
    Ljunggren, Östen
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Mellström, D.
    Lane, N. E.
    Zmuda, J. M.
    Nielsen, C.
    Orwoll, E.
    Lorentzon, M.
    Ohlsson, C.
    Jansson, J-O.
    A variant near the interleukin-6 gene is associated with fat mass in Caucasian men2010In: International Journal of Obesity, ISSN 0307-0565, E-ISSN 1476-5497, Vol. 34, no 6, p. 1011-1019Article in journal (Refereed)
    Abstract [en]

    Context:Regulation of fat mass appears to be associated with immune functions. Studies of knockout mice show that endogenous interleukin (IL)-6 can suppress mature-onset obesity.Objective:To systematically investigate associations of single nucleotide polymorphisms (SNPs) near the IL-6 (IL6) and IL-6 receptor (IL6R) genes with body fat mass, in support for our hypothesis that variants of these genes can be associated with obesity.Design and Study Subjects:The Gothenburg Osteoporosis and Obesity Determinants (GOOD) study is a population-based cross-sectional study of 18- to 20-year-old men (n=1049), from the Gothenburg area (Sweden). Major findings were confirmed in two additional cohorts consisting of elderly men from the Osteoporotic Fractures in Men (MrOS) Sweden (n=2851) and MrOS US (n=5611) multicenter population-based studies.Main Outcome:The genotype distributions and their association with fat mass in different compartments, measured with dual-energy X-ray absorptiometry.Results:Out of 18 evaluated tag SNPs near the IL6 and IL6R genes, a recently identified SNP rs10242595 G/A (minor allele frequency=29%) 3' of the IL6 gene was negatively associated with the primary outcome total body fat mass (effect size -0.11 standard deviation (s.d.) units per A allele, P=0.02). This negative association with fat mass was also confirmed in the combined MrOS Sweden and MrOS US cohorts (effect size -0.05 s.d. units per A allele, P=0.002). When all three cohorts were combined (n=8927, Caucasian subjects), rs10242595(*)A showed a negative association with total body fat mass (effect size -0.05 s.d. units per A allele, P<0.0002). Furthermore, the rs10242595(*)A was associated with low body mass index (effect size -0.03, P<0.001) and smaller regional fat masses. None of the other SNPs investigated in the GOOD study were reproducibly associated with body fat.Conclusions:The IL6 gene polymorphism rs10242595(*)A is associated with decreased fat mass in three combined cohorts of 8927 Caucasian men.

  • 2. Atroshi, Isam
    et al.
    Ahlander, Fredrik
    Billsten, Mats
    Ahlborg, Henrik G.
    Mellström, Dan
    Ohlsson, Claes
    Ljunggren, Östen
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Karlsson, Magnus K.
    Low calcaneal bone mineral density and the risk of distal forearm fracture in women and men: a population-based case-control study2009In: Bone, ISSN 8756-3282, E-ISSN 1873-2763, Vol. 45, no 4, p. 789-793Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: We used dual X-ray absorptiometry (DXA) to measure calcaneal bone mineral density (BMD) and estimate the prevalence of osteoporosis in a population with distal forearm fracture and a normative cohort. METHODS: Patients 20 to 80 years of age with distal forearm fracture treated at one emergency hospital during two consecutive years were invited to calcaneal BMD measurement; 270 women (81%) and 64 men (73%) participated. A DXA heel scanner estimated BMD (g/cm(2)) and T-scores. Osteoporosis was defined as T-score< or =-2.5 SD. Of the fracture cohort, 254 women aged 40-80 years and 27 men aged 60-80 years were compared with population-based control cohorts comprising 171 women in the age groups 50, 60, 70 and 80 years and 75 men in the age groups 60, 70, and 80 years. RESULTS: In the fracture population no woman below 40 years or man below 60 years of age had osteoporosis. In women aged 40-80 years the prevalence of osteoporosis in the distal forearm fracture cohort was 34% and in the population-based controls was 25%; the age-adjusted prevalence ratio (PR) was 1.32 (95% CI 1.00-1.76). In the subgroup of women aged 60-80 years the age-adjusted prevalence ratio of osteoporosis was 1.28 (95% CI 0.95-1.71). In men aged 60-80 years the prevalence of osteoporosis in the fracture cohort was 44% and in the population-based controls was 8% (PR 6.31, 95% CI 2.78-14.4). The age-adjusted odds ratio for fracture associated with a 1-SD reduction in calcaneal BMD was in women aged 40-80 years 1.4 (95% CI 1.1-1.8), in the subgroup of women aged 60-80 years 1.2 (95% CI 0.95-1.6), and in men aged 60-80 years 2.6 (95% CI 1.7-4.1). Among those aged 60-80 years the area under the ROC curve was in women 0.56 (95% CI 0.49-0.63) and in men 0.80 (95% CI 0.70-0.80). CONCLUSIONS: The age-adjusted prevalence of osteoporosis based on calcaneal BMD is higher in individuals with distal forearm fracture than in population-based controls. BMD impairment is associated with increased odds ratio for forearm fracture in both women and men but the differences between cases and controls are more pronounced in men than in women, which may have implications in fracture prevention.

  • 3.
    Banefelt, J.
    et al.
    Quantify Res, Stockholm, Sweden..
    Akesson, K.
    Lund Univ, Dept Orthopaed, Skane Univ Hosp, Malmo, Sweden..
    Ljunggren, Östen
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology and mineral metabolism.
    Spangeus, A.
    Linkoping Univ, Dept Endocrinol, Dept Med & Hlth Sci, Linkoping, Sweden..
    Karlsson, L.
    Quantify Res, Stockholm, Sweden..
    Strom, O.
    Quantify Res, Stockholm, Sweden.;Karolinska Inst, Dept Learning Informat Management & Eth, Stockholm, Sweden..
    Ortsater, G.
    Quantify Res, Stockholm, Sweden..
    Libanati, C.
    UCB Pharma, Brussels, Belgium..
    Toth, E.
    UCB Pharma, Brussels, Belgium..
    Short-Term Fracture (Fx) Incidence And Risk Factors Following Fracture In A Swedish Database Study2017In: Osteoporosis International, ISSN 0937-941X, E-ISSN 1433-2965, Vol. 28, p. S365-S365Article in journal (Other academic)
  • 4. Binkley, Neil
    et al.
    Ringe, Johann D.
    Reed, John I.
    Ljunggren, Östen
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Holick, Michael F.
    Minne, Helmut W.
    Liu, Minzhi
    Lamotta, Amy
    West, Joseph A.
    Santora, Arthur C.
    Alendronate/vitamin D3 70 mg/2800 IU with and without additional 2800 IU vitamin D3 for osteoporosis: results from the 24-week extension of a 15-week randomized, controlled trial2009In: Bone, ISSN 8756-3282, E-ISSN 1873-2763, Vol. 44, no 4, p. 639-647Article in journal (Refereed)
    Abstract [en]

    Although vitamin D supplementation is a fundamental part of osteoporosis treatment, many patients do not regularly take adequate amounts. A once-weekly (OW) alendronate (ALN) preparation that includes 2800 IU of vitamin D3 in a single combination tablet (ALN+D2800) is available for treating patients and ensuring intake of vitamin D that is consistent with existing guidelines. This randomized, double-blind study extension was conducted to evaluate the safety and tolerability of ALN+D2800 and ALN+D2800 plus an additional 2800 IU vitamin D3 single tablet supplement (ALN+D5600) administered for 24 weeks in men and postmenopausal women with osteoporosis previously treated OW for 15 weeks with either ALN or ALN+D2800. The primary endpoint was the proportion of participants who developed hypercalciuria (defined as a 24-hour urine calcium >300 mg in women or >350 mg in men and an increase of >25% versus randomization baseline) at week 39. The key secondary endpoint was the proportion of participants with vitamin D insufficiency (serum 25(OH)D <15 ng/mL [37.4 nmol/L]) at the end of the study. Hypercalciuria incidence (4.2% [ALN+D5600] vs. 2.8% [ALN+D2800]), did not differ between groups (p = 0.354). No participants developed hypercalcemia. Among the participants with vitamin D insufficiency at the week 0 baseline, the prevalence of insufficiency at the end of the study was reduced by 92% in the ALN+D5600 group and by 86% in the ALN+D2800 group. The incidences of clinical adverse experiences, including drug-related adverse experiences, were similar in both groups. In subjects previously treated with ALN+D2800 for 15 weeks, the addition of 2800 IU D3 for 24 weeks did not produce hypercalcemia nor increase the risk of hypercalciuria.

  • 5. Bolinder, J.
    et al.
    Ljunggren, Östen
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology and mineral metabolism.
    Johansson, L.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Wilding, J.
    Langkilde, A. M.
    Sjöstrom, C. D.
    Sugg, J.
    Parikh, S.
    Dapagliflozin maintains glycaemic control while reducing weight and body fat mass over 2 years in patients with type 2 diabetes mellitus inadequately controlled on metformin2014In: Diabetes, obesity and metabolism, ISSN 1462-8902, E-ISSN 1463-1326, Vol. 16, no 2, p. 159-169Article in journal (Refereed)
    Abstract [en]

    Aims

    Dapagliflozin, a highly selective inhibitor of sodium-glucose cotransporter 2 (SGLT2), reduces hyperglycaemia and weight in patients with type2 diabetes mellitus (T2DM) by increasing urinary glucose excretion. Long-term glycaemic control, body composition and bone safety were evaluated in patients with T2DM after 102 weeks of dapagliflozin treatment.

    Methods

    This randomized, double-blind, placebo-controlled study (NCT00855166) enrolled patients with T2DM [mean: age 60.7 years; HbA1c 7.2%; body mass index (BMI) 31.9 kg/m(2); body weight 91.5 kg] inadequately controlled on metformin. Patients (N=182) were randomly assigned 1:1 to receive dapagliflozin 10 mg/day or placebo added to open-label metformin for a 24-week double-blind treatment period followed by a 78-week site- and patient-blinded extension period. At week 102, changes from baseline in HbA1c, weight, waist circumference, total body fat mass as measured by dual-energy X-ray absorptiometry (DXA), serum markers of bone turnover, bone mineral density (BMD) as measured by DXA, and adverse events were evaluated.

    Results

    A total of 140 patients (76.9%) completed the study. Over 102 weeks, dapagliflozin-treated patients showed reductions in HbA1c by -0.3%, weight by -4.54 kg, waist circumference by -5.0 cm and fat mass by -2.80 kg without increase in rate of hypoglycaemia. Compared with placebo, no meaningful changes from baseline in markers of bone turnover or BMD were identified over 102 weeks. One fracture occurred in each treatment group. The frequency of urinary tract infection (UTI) and genital infection was similar in both treatment groups.

    Conclusions

    Over 102 weeks, dapagliflozin improved glycaemic control, and reduced weight and fat mass, without affecting markers of bone turnover or BMD in patients with T2DM inadequately controlled on metformin.

  • 6. Bolinder, Jan
    et al.
    Ljunggren, Östen
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Metabolic Bone Diseases.
    Kullberg, Joel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Johansson, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Wilding, John
    Langkilde, Anna Maria
    Sugg, Jennifer
    Parikh, Shamik
    Effects of dapagliflozin on body weight, total fat mass, and regional adipose tissue distribution in patients with type 2 diabetes mellitus with inadequate glycemic control on metformin2012In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 97, no 3, p. 1020-1031Article in journal (Refereed)
    Abstract [en]

    Context:

    Dapagliflozin, a selective sodium-glucose cotransporter 2 (SGLT2) inhibitor, reduces hyperglycemia in patients with type 2 diabetes mellitus (T2DM) by increasing urinary glucose excretion, and weight loss is a consistent associated finding.

    Objectives:

    Our objectives were to confirm weight loss with dapagliflozin and establish through body composition measurements whether weight loss is accounted for by changes in fat or fluid components.

    Design and Setting:

    This was a 24-wk, international, multicenter, randomized, parallel-group, double-blind, placebo-controlled study with ongoing 78-wk site- and patient-blinded extension period at 40 sites in five countries.

    Patients:

    Included were 182 patients with T2DM (mean values: women 63.3 and men 58.6 yr of age; hemoglobin A1c 7.17%, body mass index 31.9 kg/m2, and body weight 91.5 kg) inadequately controlled on metformin.

    Intervention:

    Dapagliflozin 10 mg/d or placebo was added to open-label metformin for 24 wk.

    Main Outcome Measures:

    Primary endpoint was total body weight (TBW) change from baseline at wk 24. Key secondary endpoints were waist circumference and dual-energy x-ray absorptiometry total-body fat mass (FM) changes from baseline at wk 24, and patient proportion achieving body weight reduction of at least 5% at wk 24. In a subset of patients, magnetic resonance assessment of visceral adipose tissue (VAT) and sc adipose tissue (SAT) volume and hepatic lipid content were also evaluated.

    Results:

    At wk 24, placebo-corrected changes with dapagliflozin were as follows: TBW, −2.08 kg [95% confidence interval (CI) = −2.84 to −1.31; P < 0.0001]; waist circumference, −1.52 cm (95% CI = −2.74 to −0.31; P = 0.0143); FM, −1.48 kg (95% CI = −2.22 to −0.74; P = 0.0001); proportion of patients achieving weight reduction of at least 5%, +26.2% (95% CI = 15.5 to 36.7; P < 0.0001); VAT, −258.4 cm3 (95% CI = −448.1 to −68.6; nominal P = 0.0084); SAT, −184.9 cm3 (95% CI = −359.7 to −10.1; nominal P = 0.0385). In the dapagliflozin vs. placebo groups, respectively, serious adverse events were reported in 6.6 vs. 1.1%; events suggestive of vulvovaginitis, balanitis, and related genital infection in 3.3 vs. 0%; and lower urinary tract infections in 6.6 vs. 2.2%.

    Conclusions:

    Dapagliflozin reduces TBW, predominantly by reducing FM, VAT and SAT in T2DM inadequately controlled with metformin.

  • 7. Boonen, S
    et al.
    Bischoff-Ferrari, H A
    Cooper, C
    Lips, P
    Ljunggren, O
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
    Meunier, P J
    Reginster, J-Y
    Addressing the musculoskeletal components of fracture risk with calcium and vitamin D: a review of the evidence.2006In: Calcif Tissue Int, ISSN 0171-967X, Vol. 78, no 5, p. 257-70Article in journal (Refereed)
  • 8.
    Borgström, F.
    et al.
    Quantify Res, Stockholm, Sweden..
    Olafsson, G.
    Quantify Res, Stockholm, Sweden..
    Jonsson, E.
    Quantify Res, Stockholm, Sweden..
    Ström, O.
    Quantify Res, Stockholm, Sweden..
    Ljunggren, Östen
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology and mineral metabolism.
    Akesson, K.
    Skane Univ Hosp, Dept Orthoped, Lund, Sweden.;Lund Univ, Clin Sci Malmo, Lund, Sweden..
    Spangeus, A.
    Linkoping Univ, Dept Med & Hlth Sci, Linkoping, Sweden..
    Kanis, J. A.
    Univ Sheffield, Sch Med, Ctr Metab Bone Dis, Sheffield, S Yorkshire, England..
    A Simulation Model For The Treatment Pathway Of Osteoporosis2016In: Osteoporosis International, ISSN 0937-941X, E-ISSN 1433-2965, Vol. 27, p. S60-S60Article in journal (Other academic)
  • 9.
    Brändström, Helena
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Gerdhem, P.
    Stiger, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Obrant, K. J.
    Melhus, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Ljunggren, Östen
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Kindmark, Andreas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Åkesson, K.
    Single nucleotide polymorphisms in the human gene for osteoprotegerin are not related to bone mineral density or fracture in elderly women2004In: Calcified Tissue International, ISSN 0171-967X, E-ISSN 1432-0827, Vol. 74, no 1, p. 18-24Article in journal (Refereed)
    Abstract [en]

    Osteoprotegerin (OPG), a secreted member of the tumor necrosis factor receptor family, is a potent inhibitor of osteoclast activation and differentiation. In animal models OPG prevents bone loss, and in humans bone resorption can be reduced by injections of OPG. OPG may also play a role in cardiovascular disease since mice lacking the OPG gene display arterial calcification. In a screening effort of the OPG gene, we recently discovered a single nucleotide polymorphism in the promoter region of OPG (T950C), and reported an association with vascular morphology and function in 59 healthy individuals. Due to the pronounced effect of OPG on bone turnover, the present study was conducted to investigate whether OPG polymorphisms are also associated with bone mineral density or with fracture. The relationship between single nucleotide polymorphisms in the promoter region of OPG (T950C) and the first intron (C1217T), and bone mineral density, measured by DXA in the hip or spine or ultrasound of the heel, was investigated in the Malmö OPRA-study of 1044 women, all 75 years old. The possible relation to fracture incidence was also analyzed. Among the 858 and 864 individuals respectively, genotyped, no significant associations between the investigated single nucleotide polymorphisms and bone mineral density measurements (T950C P = 0.50-0.64, C1217T P = 0.51-1.00), quantitative ultrasound measurements of the calcaneus, or fractures (T950C P = 0.61-0.66, C1217T P = 0.14-0.33) were found. Thus, our results show that polymorphisms in the OPG gene, one of which has previously been found to be associated with cardiovascular morphology and function, are not associated with bone mineral density in elderly Swedish women.

  • 10.
    Carlzon, Daniel
    et al.
    Univ Gothenburg, Inst Med, Sahlgrenska Acad CBAR, Ctr Bone & Arthrit Res, Gothenburg, Sweden..
    Svensson, Johan
    Univ Gothenburg, Inst Med, Sahlgrenska Acad CBAR, Ctr Bone & Arthrit Res, Gothenburg, Sweden..
    Petzold, Max
    Univ Gothenburg, Sahlgrenska Acad, Ctr Appl Biostat, Gothenburg, Sweden..
    Karlsson, Magnus K.
    Lund Univ, Skane Univ Hosp, Dept Orthopaed & Clin Sci, Clin & Mol Osteoporosis Res Unit, Malmo, Sweden..
    Ljunggren, Östen
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology and mineral metabolism.
    Haghsheno, Mohammad-Ali
    Univ Gothenburg, Inst Clin Sci, Dept Urol, Gothenburg, Sweden..
    Damber, Jan-Erik
    Univ Gothenburg, Inst Clin Sci, Dept Urol, Gothenburg, Sweden..
    Mellström, Dan
    Univ Gothenburg, Inst Med, Sahlgrenska Acad CBAR, Ctr Bone & Arthrit Res, Gothenburg, Sweden..
    Ohlsson, Claes
    Univ Gothenburg, Inst Med, Sahlgrenska Acad CBAR, Ctr Bone & Arthrit Res, Gothenburg, Sweden..
    Insulin-like growth factor I and risk of incident cancer in elderly men - results from MrOS (Osteoporotic Fractures in Men) in Sweden2016In: Clinical Endocrinology, ISSN 0300-0664, E-ISSN 1365-2265, Vol. 84, no 5, p. 764-770Article in journal (Refereed)
    Abstract [en]

    ObjectiveStudies of the association between circulating IGF-I and cancer risk have shown conflicting results. We have previously observed a U-shaped association between IGF-I and cancer mortality. This study test the hypotheses of a U-shaped association between IGF-I and incident cancer. DesignElderly men (2368), randomly recruited from the general community. MethodsIGF-I was measured in a cohort of elderly men. Complete data for incident cancer were obtained from the Swedish Cancer Registry. Statistical analyses included Cox proportional hazards regressions with or without a spline approach. ResultsThree hundred and sixty-nine participants had incident cancer after baseline. Prostate cancer was most frequent (n = 140). There was no association between serum IGF-I and all cancer or prostate cancer incidence. However, there was a nonlinear association between IGF-I and nonprostate cancer incidence (P = <005). Exploratory analyses were performed for low and high serum IGF-I (quintiles 1 and 5) vs intermediate (quintiles 2-4, referent). There was a tendency of increased nonprostate cancer risk in men with high IGF-I (HR = 126, 95% confidence interval (CI): 092-171, P = 015). After excluding participants with follow-up of less than 26 years (half median follow-up time), to control for potential diagnostic delay, the association was statistically significant (HR = 155, CI: 103-235). ConclusionThere was a significant nonlinear association between IGF-I and nonprostate cancer. No association between IGF-I and prostate cancer was observed. Future studies are warranted to further investigate this nonlinear association, including whether IGF-I concentration is a reproducible, and useful, risk marker of nonprostate cancer.

  • 11. Carlzon, Daniel
    et al.
    Svensson, Johan
    Petzold, Max
    Karlsson, Magnus K.
    Ljunggren, Östen
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology and mineral metabolism.
    Tivesten, Asa
    Mellstrom, Dan
    Ohlsson, Claes
    Both Low and High Serum IGF-1 Levels Associate With Increased Risk of Cardiovascular Events in Elderly Men2014In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 99, no 11, p. E2308-E2316Article in journal (Refereed)
    Abstract [en]

    Context: Most previous prospective studies suggest that low serum IGF-1 associates with increased risk of cardiovascular disease (CVD) events whereas other studies suggest that high serum IGF-1 associates with increased risk of CVD events. Objective: We tested the hypothesis that not only low, but also high serum IGF-1 levels associate with increased risk of CVD events in elderly men. Setting and Design: Serum IGF-1 levels were measured in 2901 elderly men (age 69-81 years) included in the Swedish cohort of the prospective, population-based Osteoporotic Fractures in Men Study (MrOS), Sweden cohort. Data for CVD events were obtained from national Swedish registers with no loss of followup. Results: During followup (median, 5.1 y) 589 participants experienced a CVD event. The association between serum IGF-1 and risk of CVD events was nonlinear, and restricted cubic spline Cox regression analysis revealed a U-shaped association between serum IGF-1 levels and CVD events (P < .01 for nonlinearity). Low as well as high serum IGF-1 (quintile 1 or 5 vs quintiles 2-4) significantly associated with increased risk for CVD events (hazard ratio [HR] = 1.25, 95% confidence interval, [CI], 1.02-1.54; and HR = 1.35, 95% CI 1.10-1.66, respectively). These associations remained after adjustment for prevalent CVD and multiple risk factors. High serum IGF-1 associated with increased risk of coronary heart disease (CHD) events but not with risk of cerebrovascular events. Conclusions: Both low and high serum IGF-1 levels are risk markers for CVD events in elderly men. The association between high serum IGF-1 and CVD events is mainly driven by CHD events.

  • 12. Coviello, Andrea D.
    et al.
    Haring, Robin
    Wellons, Melissa
    Vaidya, Dhananjay
    Lehtimaki, Terho
    Keildson, Sarah
    Lunetta, Kathryn L.
    He, Chunyan
    Fornage, Myriam
    Lagou, Vasiliki
    Mangino, Massimo
    Onland-Moret, N. Charlotte
    Chen, Brian
    Eriksson, Joel
    Garcia, Melissa
    Mei, Yong
    Koster, Annemarie
    Lohman, Kurt
    Lyytikainen, Leo-Pekka
    Petersen, Ann-Kristin
    Prescott, Jennifer
    Stolk, Lisette
    Vandenput, Liesbeth
    Wood, Andrew R.
    Zhuang, Wei Vivian
    Ruokonen, Aimo
    Hartikainen, Anna-Liisa
    Pouta, Anneli
    Bandinelli, Stefania
    Biffar, Reiner
    Brabant, Georg
    Cox, David G.
    Chen, Yuhui
    Cummings, Steven
    Ferrucci, Luigi
    Gunter, Marc J.
    Hankinson, Susan E.
    Martikainen, Hannu
    Hofman, Albert
    Homuth, Georg
    Illig, Thomas
    Jansson, John-Olov
    Johnson, Andrew D.
    Karasik, David
    Karlsson, Magnus
    Kettunen, Johannes
    Kiel, Douglas P.
    Kraft, Peter
    Liu, Jingmin
    Ljunggren, Östen
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Metabolic Bone Diseases.
    Lorentzon, Mattias
    Maggio, Marcello
    Markus, Marcello R. P.
    Mellstrom, Dan
    Miljkovic, Iva
    Mirel, Daniel
    Nelson, Sarah
    Papunen, Laure Morin
    Peeters, Petra H. M.
    Prokopenko, Inga
    Raffel, Leslie
    Reincke, Martin
    Reiner, Alex P.
    Rexrode, Kathryn
    Rivadeneira, Fernando
    Schwartz, Stephen M.
    Siscovick, David
    Soranzo, Nicole
    Stockl, Doris
    Tworoger, Shelley
    Uitterlinden, Andre G.
    van Gils, Carla H.
    Vasan, Ramachandran S.
    Wichmann, H. -Erich
    Zhai, Guangju
    Bhasin, Shalender
    Bidlingmaier, Martin
    Chanock, Stephen J.
    De Vivo, Immaculata
    Harris, Tamara B.
    Hunter, David J.
    Kahonen, Mika
    Liu, Simin
    Ouyang, Pamela
    Spector, Tim D.
    van der Schouw, Yvonne T.
    Viikari, Jorma
    Wallaschofski, Henri
    McCarthy, Mark I.
    Frayling, Timothy M.
    Murray, Anna
    Franks, Steve
    Jarvelin, Marjo-Riitta
    de Jong, Frank H.
    Raitakari, Olli
    Teumer, Alexander
    Ohlsson, Claes
    Murabito, Joanne M.
    Perry, John R. B.
    A Genome-Wide Association Meta-Analysis of Circulating Sex Hormone-Binding Globulin Reveals Multiple Loci Implicated in Sex Steroid Hormone Regulation2012In: PLOS Genetics, ISSN 1553-7390, E-ISSN 1553-7404, Vol. 8, no 7, p. e1002805-Article in journal (Refereed)
    Abstract [en]

    Sex hormone-binding globulin (SHBG) is a glycoprotein responsible for the transport and biologic availability of sex steroid hormones, primarily testosterone and estradiol. SHBG has been associated with chronic diseases including type 2 diabetes (T2D) and with hormone-sensitive cancers such as breast and prostate cancer. We performed a genome-wide association study (GWAS) meta-analysis of 21,791 individuals from 10 epidemiologic studies and validated these findings in 7,046 individuals in an additional six studies. We identified twelve genomic regions (SNPs) associated with circulating SHBG concentrations. Loci near the identified SNPs included SHBG (rs12150660, 17p13.1, p = 1.8x10(-106)), PRMT6 (rs17496332, 1p13.3, p=1.4x10(-11)), GCKR (rs780093, 2p23.3, p=2.2x10(-16)), ZBTB10 (rs440837, 8q21.13, p=3.4x10(-09)), JMJD1C (rs7910927, 10q21.3, p=6.1x10(-35)), SLCO1B1 (rs4149056, 12p12.1, p=1.9x10(-08)), NR2F2 (rs8023580, 15q26.2, p=8.3x10(-12)), ZNF652 (rs2411984, 17q21.32, p=3.5x10(-14)), TDGF3 (rs1573036, Xq22.3, p=4.1x10(-14)), LHCGR (rs10454142, 2p16.3, p=1.3x10(-07)), BAIAP2L1 (rs3779195, 7q21.3, p=2.7x10(-08)), and UGT2B15 (rs293428, 4q13.2, p=5.5x10(-06)). These genes encompass multiple biologic pathways, including hepatic function, lipid metabolism, carbohydrate metabolism and T2D, androgen and estrogen receptor function, epigenetic effects, and the biology of sex steroid hormone-responsive cancers including breast and prostate cancer. We found evidence of sex-differentiated genetic influences on SHBG. In a sex-specific GWAS, the loci 4q13.2-UGT2B15 was significant in men only (men p = 2.5x10(-08), women p=0.66, heterogeneity p=0.003). Additionally, three loci showed strong sex-differentiated effects: 17p13.1-SHBG and Xq22.3-TDGF3 were stronger in men, whereas 8q21.12-ZBTB10 was stronger in women. Conditional analyses identified additional signals at the SHBG gene that together almost double the proportion of variance explained at the locus. Using an independent study of 1,129 individuals, all SNPs identified in the overall or sex-differentiated or conditional analyses explained similar to 15.6% and similar to 8.4% of the genetic variation of SHBG concentrations in men and women, respectively. The evidence for sex-differentiated effects and allelic heterogeneity highlight the importance of considering these features when estimating complex trait variance.

  • 13. Ellegaard, Maria
    et al.
    Karlsson, Magnus
    Lorentzon, Mattias
    Ohlsson, Claes
    Mellstrom, Dan
    Ljunggren, Östen
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology and mineral metabolism.
    Schwarz, Peter
    Jorgensen, Niklas Rye
    Single-nucleotide polymorphism in the P2Y(2) receptor gene is associated with bone mineral density in a cohort of Swedish elderly men2014In: Purinergic Signalling Purinergic Signalling, ISSN 1573-9538, E-ISSN 1573-9546, Vol. 10, no 4, p. 751-751, article id B015Article in journal (Other academic)
  • 14. Eriksson, A. L.
    et al.
    Lorentzon, M.
    Mellström, D.
    Vandenput, L.
    Swanson, C.
    Andersson, N.
    Hammond, G. L.
    Jakobsson, J.
    Rane, A.
    Orwoll, E. S.
    Ljunggren, Östen
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Johnell, O.
    Labrie, F.
    Windahl, S. H.
    Ohlsson, C.
    SHBG gene promoter polymorphisms in men are associated with serum sex hormone-binding globulin, androgen and androgen metabolite levels, and hip bone mineral density2006In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 91, no 12, p. 5029-5037Article in journal (Refereed)
    Abstract [en]

    Context: SHBG regulates free sex steroid levels, which in turn regulate skeletal homeostasis. Twin studies have demonstrated that genetic factors largely account for interindividual variation in SHBG levels. Glucuronidated androgen metabolites have been proposed as markers of androgenic activity. Objective: Our objective was to investigate whether polymorphisms in the SHBG gene promoter [(TAAAA)n microsatellite and rs1799941 single-nucleotide polymorphism] are associated with serum levels of SHBG, sex steroids, or bone mineral density (BMD) in men. Design and Study Subjects: We conducted a population-based study of two cohorts of Swedish men: elderly men (MrOS Sweden; n ≅3000; average age, 75.4 yr) and young adult men (GOOD study; n = 1068; average age, 18.9 yr). Main Outcome Measures: We measured serum levels of SHBG, testosterone, estradiol, dihydrotestosterone, 5α-androstane-3α,17β-diol glucuronides, androsterone glucuronide, and BMD determined by dual-energy x-ray absorptiometry. Results: In both cohorts, (TAAAA)n and rs1799941 genotypes were associated with serum levels of SHBG (P < 0.001), dihydrotestosterone (P < 0.05), and 5α-androstane-3α,17β-diol glucuronides (P < 0.05). In the elderly men, they were also associated with testosterone and BMD at all hip bone sites. The genotype associated with high levels of SHBG was also associated with high BMD. Interestingly, male mice overexpressing human SHBG had increased cortical bone mineral content in the femur, suggesting that elevated SHBG levels may cause increased bone mass. Conclusions: Our findings demonstrate that polymorphisms in the SHBG promoter predict serum levels of SHBG, androgens, and glucuronidated androgen metabolites, and hip BMD in men.

  • 15. Eriksson, Anna L.
    et al.
    Lorentzon, Mattias
    Vandenput, Liesbeth
    Labrie, Fernand
    Lindersson, Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine.
    Syvänen, Ann-Christine
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine.
    Orwoll, Eric S.
    Cummings, Steven R.
    Zmuda, Joseph M.
    Ljunggren, Östen
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Karlsson, Magnus K.
    Mellström, Dan
    Ohlsson, Claes
    Genetic variations in sex steroid-related genes as predictors of serum estrogen levels in men2009In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 94, no 3, p. 1033-1041Article in journal (Refereed)
    Abstract [en]

    Context:

    The risk of many conditions, including prostate cancer, breast cancer, and osteoporosis, is associated with serum levels of sex steroids.

    Objective:

    The aim of the study was to identify genetic variations in sex steroid-related genes that are associated with serum levels of estradiol (E2) and/or testosterone in men.

    Design:

    Genotyping of 604 single nucleotide polymorphisms in 50 sex steroid-related candidate genes was performed in the Gothenburg Osteoporosis and Obesity Determinants (GOOD) study (n = 1041 men; age, 18.9 ± 0.6 yr). Replications of significant associations were performed in the Osteoporotic Fractures in Men (MrOS) Sweden study (n = 2568 men; age, 75.5 ± 3.2 yr) and in the MrOS US study (n = 1922 men; age, 73.5 ± 5.8 yr). Serum E2, testosterone, and estrone (E1) levels were analyzed using gas chromatography/mass spectrometry.

    Results:

    The screening in the GOOD cohort identified the single nucleotide polymorphism rs2470152 in intron 1 of the CYP19 gene, which codes for aromatase, responsible for the final step of the biosynthesis of E2 and E1, to be most significantly associated with serum E2 levels (P = 2 × 10−6). This association was confirmed both in the MrOS Sweden study (P = 9 × 10−7) and in the MrOS US study (P = 1 × 10−4). When analyzed in all subjects (n = 5531), rs2470152 was clearly associated with both E2 (P = 2 × 10−14) and E1 (P = 8 × 10−19) levels. In addition, this polymorphism was modestly associated with lumbar spine BMD (P < 0.01) and prevalent self-reported fractures (P < 0.05).

    Conclusions:

    rs2470152 of the CYP19 gene is clearly associated with serum E2 and E1 levels in men.

  • 16. Eriksson, Anna L.
    et al.
    Mellström, Dan
    Lorentzon, Mattias
    Orwoll, Eric S.
    Redlund-Johnell, Inga
    Grundberg, Elin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Holmberg, Anna
    Ljunggren, Östen
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Karlsson, Magnus K.
    Ohlsson, Claes
    The COMT val158met polymorphism is associated with prevalent fractures in Swedish men2008In: Bone, ISSN 8756-3282, E-ISSN 1873-2763, Vol. 42, no 1, p. 107-112Article in journal (Refereed)
    Abstract [en]

    Introduction: Sex steroids are important for growth and maintenance of the skeleton. Catechol-O-methyltransferase (COMT) is an estrogen degrading enzyme. The COMT val158met polymorphism results in a 60-75% difference in enzyme activity between the val (high activity=H) and met (low activity=L) variants. We have previously reported that this polymorphism is associated with bone mineral density (BMD) in young men. The aim of this study was to investigate associations between COMT val158met, BMD and fractures in elderly men. Methods: Population-based study of Swedish men 75.4, SD 3.2, years of age. Fractures were reported using standardized questionnaires. Fracture and genotype data were available from 2822 individuals. Results: Total number of individuals with self-reported fracture was 989 (35.0%). Prevalence of >= 1 fracture was 37.2% in COMTLL, 35.7% in COMTHL and 30.4% in COMTHH (p<0.05). Early fractures (<= 50 years of age) were less common in COMTHH than in the combined COMTLL+HL genotype, OR 0.78 (95% CI 0.63-0.97). No associations were found for late fractures (>50 years of age). The OR for fracture of the non-weight bearing skeleton in COMTHH compared with COMTLL+HL was 0.74 (95% CI 0.59-0.92). No associations between COMT val158met and BMD were found in this cohort of elderly men. Conclusions: The COMT val158met polymorphism is associated with life time fracture prevalence in elderly Swedish men. This association is mainly driven by early fractures (<= 50 years of age).

  • 17. Eriksson, Anna L.
    et al.
    Movérare-Skrtic, Sofia
    Ljunggren, Östen
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology and mineral metabolism.
    Karlsson, Magnus
    Mellström, Dan
    Ohlsson, Claes
    High-Sensitivity CRP Is an Independent Risk Factor for All Fractures and Vertebral Fractures in Elderly Men: The MrOS Sweden Study2014In: Journal of Bone and Mineral Research, ISSN 0884-0431, E-ISSN 1523-4681, Vol. 29, no 2, p. 418-423Article in journal (Refereed)
    Abstract [en]

    Epidemiological studies have shown low-grade inflammation measured by high-sensitivity C-reactive protein (hs-CRP) to be associated with fracture risk in women. However, it is still unclear whether hs-CRP is also associated with fracture risk in men. We therefore measured serum levels of hs-CRP in 2910 men, mean age 75 years, included in the prospective population-based MrOS Sweden cohort. Study participants were divided into tertile groups based on hs-CRP level. Fractures occurring after the baseline visit were validated (average follow-up 5.4 years). The incidence for having at least one fracture after baseline was 23.9 per 1000 person-years. In Cox proportional hazard regression analyses adjusted for age, hs-CRP was related to fracture risk. The hazard ratio (HR) of fracture for the highest tertile of hs-CRP, compared with the lowest and the medium tertiles combined, was 1.48 (95% CI, 1.20-1.82). Multivariate adjustment for other risk factors for fractures had no major effect on the associations between hs-CRP and fracture. Results were essentially unchanged after exclusion of subjects with hs-CRP levels greater than 7.5mg/L, as well as after exclusion of subjects with a first fracture within 3 years of follow-up, supporting that the associations between hs-CRP and fracture risk were not merely a reflection of a poor health status at the time of serum sampling. Femoral neck bone mineral density (BMD) was not associated with hs-CRP, and the predictive role of hs-CRP for fracture risk was essentially unchanged when femoral neck BMD was added to the model (HR, 1.37; 95% CI, 1.09-1.72). Exploratory subanalyses of fracture type demonstrated that hs-CRP was clearly associated with clinical vertebral fractures (HR, 1.61; 95% CI, 1.12-2.29). We demonstrate, using a large prospective population-based study, that elderly men with high hs-CRP have increased risk of fractures, and that these fractures are mainly vertebral. The association between hs-CRP and fractures was independent of BMD. (c) 2014 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals, Inc. on behalf of the American Society for Bone and Mineral Research. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

  • 18. Estrada, Karol
    et al.
    Styrkarsdottir, Unnur
    Evangelou, Evangelos
    Hsu, Yi-Hsiang
    Duncan, Emma L.
    Ntzani, Evangelia E.
    Oei, Ling
    Albagha, Omar M. E.
    Amin, Najaf
    Kemp, John P.
    Koller, Daniel L.
    Li, Guo
    Liu, Ching-Ti
    Minster, Ryan L.
    Moayyeri, Alireza
    Vandenput, Liesbeth
    Willner, Dana
    Xiao, Su-Mei
    Yerges-Armstrong, Laura M.
    Zheng, Hou-Feng
    Alonso, Nerea
    Eriksson, Joel
    Kammerer, Candace M.
    Kaptoge, Stephen K.
    Leo, Paul J.
    Thorleifsson, Gudmar
    Wilson, Scott G.
    Wilson, James F.
    Aalto, Ville
    Alen, Markku
    Aragaki, Aaron K.
    Aspelund, Thor
    Center, Jacqueline R.
    Dailiana, Zoe
    Duggan, David J.
    Garcia, Melissa
    Garcia-Giralt, Natalia
    Giroux, Sylvie
    Hallmans, Goran
    Hocking, Lynne J.
    Husted, Lise Bjerre
    Jameson, Karen A.
    Khusainova, Rita
    Kim, Ghi Su
    Kooperberg, Charles
    Koromila, Theodora
    Kruk, Marcin
    Laaksonen, Marika
    Lacroix, Andrea Z.
    Lee, Seung Hun
    Leung, Ping C.
    Lewis, Joshua R.
    Masi, Laura
    Mencej-Bedrac, Simona
    Nguyen, Tuan V.
    Nogues, Xavier
    Patel, Millan S.
    Prezelj, Janez
    Rose, Lynda M.
    Scollen, Serena
    Siggeirsdottir, Kristin
    Smith, Albert V.
    Svensson, Olle
    Trompet, Stella
    Trummer, Olivia
    van Schoor, Natasja M.
    Woo, Jean
    Zhu, Kun
    Balcells, Susana
    Brandi, Maria Luisa
    Buckley, Brendan M.
    Cheng, Sulin
    Christiansen, Claus
    Cooper, Cyrus
    Dedoussis, George
    Ford, Ian
    Frost, Morten
    Goltzman, David
    Gonzalez-Macias, Jesus
    Kahonen, Mika
    Karlsson, Magnus
    Khusnutdinova, Elza
    Koh, Jung-Min
    Kollia, Panagoula
    Langdahl, Bente Lomholt
    Leslie, William D.
    Lips, Paul
    Ljunggren, Östen
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Lorenc, Roman S.
    Marc, Janja
    Mellstrom, Dan
    Obermayer-Pietsch, Barbara
    Olmos, Jose M.
    Pettersson-Kymmer, Ulrika
    Reid, David M.
    Riancho, Jose A.
    Ridker, Paul M.
    Rousseau, Francois
    Slagboom, P. Eline
    Tang, Nelson L. S.
    Urreizti, Roser
    Van Hul, Wim
    Viikari, Jorma
    Zarrabeitia, Maria T.
    Aulchenko, Yurii S.
    Castano-Betancourt, Martha
    Grundberg, Elin
    Herrera, Lizbeth
    Ingvarsson, Thorvaldur
    Johannsdottir, Hrefna
    Kwan, Tony
    Li, Rui
    Luben, Robert
    Medina-Gomez, Carolina
    Palsson, Stefan Th
    Reppe, Sjur
    Rotter, Jerome I.
    Sigurdsson, Gunnar
    van Meurs, Joyce B. J.
    Verlaan, Dominique
    Williams, Frances M. K.
    Wood, Andrew R.
    Zhou, Yanhua
    Gautvik, Kaare M.
    Pastinen, Tomi
    Raychaudhuri, Soumya
    Cauley, Jane A.
    Chasman, Daniel I.
    Clark, Graeme R.
    Cummings, Steven R.
    Danoy, Patrick
    Dennison, Elaine M.
    Eastell, Richard
    Eisman, John A.
    Gudnason, Vilmundur
    Hofman, Albert
    Jackson, Rebecca D.
    Jones, Graeme
    Jukema, J. Wouter
    Khaw, Kay-Tee
    Lehtimaki, Terho
    Liu, Yongmei
    Lorentzon, Mattias
    McCloskey, Eugene
    Mitchell, Braxton D.
    Nandakumar, Kannabiran
    Nicholson, Geoffrey C.
    Oostra, Ben A.
    Peacock, Munro
    Pols, Huibert A. P.
    Prince, Richard L.
    Raitakari, Olli
    Reid, Ian R.
    Robbins, John
    Sambrook, Philip N.
    Sham, Pak Chung
    Shuldiner, Alan R.
    Tylavsky, Frances A.
    van Duijn, Cornelia M.
    Wareham, Nick J.
    Cupples, L. Adrienne
    Econs, Michael J.
    Evans, David M.
    Harris, Tamara B.
    Kung, Annie Wai Chee
    Psaty, Bruce M.
    Reeve, Jonathan
    Spector, Timothy D.
    Streeten, Elizabeth A.
    Zillikens, M. Carola
    Thorsteinsdottir, Unnur
    Ohlsson, Claes
    Karasik, David
    Richards, J. Brent
    Brown, Matthew A.
    Stefansson, Kari
    Uitterlinden, Andre G.
    Ralston, Stuart H.
    Ioannidis, John P. A.
    Kiel, Douglas P.
    Rivadeneira, Fernando
    Genome-wide meta-analysis identifies 56 bone mineral density loci and reveals 14 loci associated with risk of fracture2012In: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 44, no 5, p. 491-501Article in journal (Refereed)
    Abstract [en]

    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 x 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 x 10(-4), Bonferroni corrected), of which six reached P < 5 x 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.

  • 19.
    Feudjo Tepie, M.
    et al.
    Amgen Ltd, Uxbridge, Middx, England..
    Banefelt, J.
    Quantify Res, Stockholm, Sweden..
    Ström, O.
    Quantify Res, Stockholm, Sweden..
    Ortsater, G.
    Quantify Res, Stockholm, Sweden..
    Ljunggren, Östen
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology and mineral metabolism.
    Åkesson, K.
    Skane Univ Hosp, Dept Orthoped, Lund, Sweden.;Lund Univ, Clin Sci Malmo, Lund, Sweden..
    Sprafka, J. M.
    Amgen Inc, Thousand Oaks, CA 91320 USA..
    Wagman, R. B.
    Amgen Inc, Thousand Oaks, CA 91320 USA..
    Denosumab (DMAB) Freedom Extension Pseudo Control Study: A Retrospective Cohort Study Of Comorbidities In Swedish Women With Postmenopausal Osteoporosis (PMO)2016In: Osteoporosis International, ISSN 0937-941X, E-ISSN 1433-2965, Vol. 27, p. S154-S154Article in journal (Other academic)
  • 20. Freyschuss, Bo
    et al.
    Ljunggren, Östen
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Mellström, Dan
    Sääf, Maria
    SBU-rapport om vitamin D och kalcium ger nytt bevisläge. Behandling minskar frakturrisk hos kvinnor över 80 år - men inte hos yngre2007In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 104, no 11, p. 858-859Article in journal (Other academic)
    Abstract [en]

    [New evidence in SBU report on vitamin D and calcium. The risk of fracture is reduced by treatment in women older than 80 years--but not in younger ones]

  • 21. Freyschuss, Bo
    et al.
    Mellström, Dan
    Sääf, Maria
    Ljunggren, Östen
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    SBUs slutsatser avseende behandling med vitamin D och kalcium står fast2007In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 104, no 43, p. 3217-3218Article in journal (Other academic)
    Abstract [en]

    [SBU's conclusions concerning vitamin D and calcium treatment unchanged]

  • 22.
    Frisk, Per
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Arvidson, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Ljunggren, Östen
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Gustafsson, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Decreased bone mineral density in young adults treated with SCT in childhood: the role of 25-hydroxyvitamin D2012In: Bone Marrow Transplantation, ISSN 0268-3369, E-ISSN 1476-5365, Vol. 47, no 5, p. 657-662Article in journal (Refereed)
    Abstract [en]

    We measured bone mineral density (BMD) with dual-energy X-ray absorptiometry in the total body, at the lumbar spine, at the femoral neck and in the total hip, in 18 young adults with a median of 18.2 years after SCT. Fifteen patients had undergone auto-SCT and all patients had received TBI. The patients had significantly lower BMD in the total body, at the femoral neck, and in the total hip compared with age- and sex-matched controls. Six of 18 patients (33%) had low bone mass (z-score <−1) at one or more measurement sites, as opposed to two of the controls (11%, P=0.29). We found no significant influence of growth hormone levels or of untreated hypogonadism on BMD variables. Levels of 25-hydroxy (25(OH)) vitamin D were lower among the patients (35.2 vs 48.8 nmol/L, P=0.044) and were significantly correlated with total body BMD in the patient group (r=0.55, P=0.021). All six patients with low bone mass had hypovitaminosis D (37 nmol/L as opposed to 4 of the 11 (36%) patients without low bone mass (P=0.035). In conclusion, we found decreased BMD in SCT survivors, which may in part be caused by 25(OH) vitamin D deficiency.

  • 23. Gerdhem, P.
    et al.
    Brändström, Helena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Stiger, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Obrant, K.
    Melhus, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Ljunggren, Östen
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Kindmark, Andreas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Åkesson, K.
    Association of the collagen type 1 (COL1A 1) Sp1 binding site polymorphism to femoral neck bone mineral density and wrist fracture in 1044 elderly Swedish women2004In: Calcified Tissue International, ISSN 0171-967X, E-ISSN 1432-0827, Vol. 74, no 3, p. 264-269Article in journal (Refereed)
    Abstract [en]

    Identification of risk factors for osteoporosis has been essential for understanding the development of osteoporosis and related fragility fractures. A polymorphism of the binding site for the transcription factor Sp1 of the collagen I alpha 1 gene (COLIA1) has shown an association to bone mass and fracture, but the findings have not been consistent, which may be related to population differences. The Sp1 polymorphism was determined in 1044 women, all 75 years old, participating in the population-based Osteoporosis Prospective Risk Assessment study in Malmö (OPRA). Bone mineral density, heel ultrasound and all previous fractures were registered. BMD was 2.7% lower in the femoral neck in women carrying at least one copy of the "s" allele ( P = 0.027). There was no difference in bone mass at any other site, weight, BMI or age at menopause. Women with a prevalent wrist fracture (n = 181) had an increased presence of the "s" allele. The odds ratio for prevalent wrist fracture was 2.73 (95% CI 1.1-6.8) for the ss homozygotes and 1.4 (95% CI 1.0-2.0) for the Ss heterozygotes when compared with the SS homozygotes. In conclusion, in this large and homogeneous cohort of 75-year-old Swedish women, there was an association among the Sp1 COLIA1 polymorphism, bone mass, and fracture. The presence of at least one copy of the "s" allele was associated with lower femoral neck BMD and previous wrist fracture and in addition, it was related to an increased risk for wrist fracture.

  • 24. Ghanei, Iman
    et al.
    Rosengren, Bjorn E.
    Hasserius, Ralph
    Nilsson, Jan-Ake
    Mellstrom, Dan
    Ohlsson, Claes
    Ljunggren, Östen
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology and mineral metabolism.
    Karlsson, Magnus K.
    The prevalence and severity of low back pain and associated symptoms in 3,009 old men2014In: European spine journal, ISSN 0940-6719, E-ISSN 1432-0932, Vol. 23, no 4, p. 814-820Article in journal (Refereed)
    Abstract [en]

    The aim of this study is to evaluate the prevalence and severity of low back pain (LBP) and the influence of sciatica and neurological deficits in old men. Mister osteoporosis Sweden includes 3,014 community-dwelling men aged 69-81 years. At study start 3,009 participants answered questions on LBP, low back pain and sciatica (LBP + SCI) or low back pain and sciatica with associated neurological deficits (LBP + SCI + NEU) during the preceding 12 months. Data are presented as proportions or medians with mid-quartile ranges. Differences between groups were tested by chi(2) test and Kruskall-Wallis test. 24 % had experienced LBP without SCI, 8 % LBP + SCI and 14 % LBP + SCI + NEU. 10 % of the men with LBP, 22 % of those with LBP + SCI, and 36 % of those with LBP + SCI + NEU rated the pain as severe (p < 0.001). 23 % of the men with LBP, 31 % of those with LBP + SCI and 50 % of those with LBP + SCI + NEU reported limitation in activity of daily living (ADL) (p < 0.001). Men with only LBP had to restrict their activities for 7 days (3-14), those with LBP + SCI 6 days (2-14) and those with LBP + SCI + NEU 10 days (3-30) (p < 0.05). The 1-year prevalence of LBP in community living men aged 69-81 years was close to 50 % but for individuals with LBP or LBP + SCI the morbidity was low with more than two-thirds having no limitations in ADL. In men with LBP + SCI + NEU more than one-third rated the pain as severe and close to half had limitations in ADL.

  • 25.
    Grundberg, E
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Carling, T
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Brändström, H
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Huang, S
    Ribom, E. L
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Ljunggren, O
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Mallmin, H
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Kindmark, A
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    A deletion polymorphism in the RIZ gene, a female sex steroid hormone receptor coactivator, exhibits decreased response to estrogen in vitro and associates with low bone mineral density in young Swedish women2004In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 89, no 12, p. 6173-6178Article in journal (Refereed)
    Abstract [en]

    Low bone mineral density (BMD) is a major risk factor for osteoporotic fracture, and the trait is under genetic control by a large number of genes. It is recognized that estrogen plays an important role in the maintenance of bone mass by binding to estrogen receptor a (ERa). RIZ1 has previously been shown to be a specific ERa coactivator and strongly enhances its function both in vivo and in vitro. We performed in vitro studies comparing the abilities of RIZ1 P704 polymorphic variants (homozygous presence, P704+; absence, P704-; heterozygosity P704+/- of a proline at position 704) to coactivate the ERa and also examined the polymorphism associated to BMD of 343 Swedish women, aged 20-39 yr. The expression vector containing P704- RIZ1 showed an impaired response in coactivating ERa in a ligand- and dose-dependent manner compared with P704+ RIZ (P < 0.0001). The genotype frequencies were 19% (P704+), 32% (P704-), and 49% (P704+/-) and were in Hardy-Weinberg equilibrium. BMD at the heel was higher in the P704+ genotype group than in the P704+/- group (P = 0.02), which was evident also after corrections for fat and lean mass (P = 0.03). We conclude that RIZ1 may be a new candidate gene for involvement in the variation seen in BMD.

  • 26.
    Grundberg, E
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Lau, E
    Lorentzson, M
    Karlsson, M
    Holmberg, A
    Groop, L
    Mellström, D
    Orwoll, E
    Mallmin, H
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Ohlsson, C
    Ljunggren, O
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Åkesson, K
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Large-scale association study between two coding LRP5 gene polymorphisms and bone phenotypes and fractures in men2007In: Osteoporosis International, ISSN 0937-941X, E-ISSN 1433-2965, Vol. 19, no 6, p. 829-837Article in journal (Refereed)
    Abstract [en]

    Summary  Herein we investigated the association between polymorphisms in the LRP5 gene and bone phenotypes and fractures in three large male cohorts based on the rationale that mutations in LRP5 cause severe bone phenotypes. Results showed an association of the Val667Met SNP with spine BMD in 3,800 young and elderly men. Introduction  The low-density lipoprotein receptor-related protein 5 (LRP5)-Wnt signalling system is of importance for regulating osteoblastic activity, which became clear after findings that inactivating mutations in LRP5 cause osteoporosis. The overall aim of this study was to investigate the association between polymorphisms in the LRP5 gene and bone mineral density (BMD) in three large cohorts of young and elderly men. Methods  The cohorts used were MrOS Sweden (n = 3014, aged 69–81 years) and MrOs Hong Kong (n = 2000, aged  > 65 years) and the Swedish GOOD study (n = 1068, aged 18–20 years). The polymorphisms Val667Met and Ala1330Val were genotyped using a TaqMan assay. Results  When combining the data from the Swedish cohorts in a meta-analysis (n = 3,800), men carrying the 667Met-allele had 3% lower BMD at lumbar spine compared with non-carriers (p < 0.05). The Val667Met SNP was not polymorphic in the Hong Kong population and thus were not included. There were no associations between the Ala1330Val SNP and bone phenotypes in the study populations. No associations between the LRP5 polymorphisms and self-reported fractures were seen in MrOs Sweden. Conclusions  Results from these three large cohorts indicate that the Val667Met polymorphism but not the Ala1330Val contributes to the observed variability in BMD in the Swedish populations.

  • 27.
    Grundberg, Elin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Brändström, Helena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Lam, Kevin C. L.
    Gurd, Scott
    Ge, Bing
    Harmsen, Eef
    Kindmark, Andreas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Ljunggren, Östen
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Mallmin, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Nilsson, Olle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Pastinen, Tomi
    Systematic assessment of the human osteoblast transcriptome in resting and induced primary cells2008In: Physiological Genomics, ISSN 1094-8341, E-ISSN 1531-2267, Vol. 33, no 3, p. 301-11Article in journal (Refereed)
    Abstract [en]

    Osteoblasts are key players in bone remodeling. The accessibility of human primary osteoblast-like cells (HObs) from bone explants makes them a lucrative model for studying molecular physiology of bone turnover, for discovering novel anabolic therapeutics, and for mesenchymal cell biology in general. Relatively little is known about resting and dynamic expression profiles of HObs, and to date no studies have been conducted to systematically assess the osteoblast transcriptome. The aim of this study was to characterize HObs and investigate signaling cascades and gene networks with genomewide expression profiling in resting and bone morphogenic protein (BMP)-2- and dexamethasone-induced cells. In addition, we compared HOb gene expression with publicly available samples from the Gene Expression Omnibus. Our data show a vast number of genes and networks expressed predominantly in HObs compared with closely related cells such as fibroblasts or chondrocytes. For instance, genes in the insulin-like growth factor (IGF) signaling pathway were enriched in HObs (P = 0.003) and included the binding proteins (IGFBP-1, -2, -5) and IGF-II and its receptor. Another HOb-specific expression pattern included leptin and its receptor (P < 10(-8)). Furthermore, after stimulation of HObs with BMP-2 or dexamethasone, the expression of several interesting genes and pathways was observed. For instance, our data support the role of peripheral leptin signaling in bone cell function. In conclusion, we provide the landscape of tissue-specific and dynamic gene expression in HObs. This resource will allow utilization of osteoblasts as a model to study specific gene networks and gene families related to human bone physiology and diseases.

  • 28.
    Grundberg, Elin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Brändström, Helena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Ribom, Eva L
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Ljunggren, Östen
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Mallmin, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Kindmark, Andreas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Genetic variation in the human vitamin D receptor is associated with muscle strength, fat mass and body weight in Swedish women2004In: European Journal of Endocrinology, ISSN 0804-4643, E-ISSN 1479-683X, Vol. 150, no 3, p. 323-328Article in journal (Refereed)
    Abstract [en]

    Objective: Bone mineral density (BMD) is under strong genetic control and a number of candidategenes have been associated with BMD. Both muscle strength and body weight are considered to beimportant predictors of BMD but far less is known about the genes affecting muscle strength andfat mass. The purpose of this study was to investigate the poly adenosine (A) repeat and the BsmISNP in the vitamin D receptor (VDR) in relation to muscle strength and body composition in healthywomen.

    Design: A population-based study of 175 healthy women aged 20–39 years was used.

    Methods: The polymorphic regions in the VDR gene (the poly A repeat and the BsmI SNP) were amplifiedby PCR. Body mass measurements (fat mass, lean mass, body weight and body mass index) andmuscle strength (quadriceps, hamstring and grip strength) were evaluated.

    Results: Individuals with shorter poly A repeat, ss and/or absence of the linked BsmI restriction site(BB) have higher hamstring strength (ss vs LL, P ¼ 0.02), body weight (ss vs LL, P ¼ 0.049) andfat mass (ss vs LL, P ¼ 0.04) compared with women with a longer poly A repeat (LL) and/or thepresence of the linked BsmI restriction site (bb).

    Conclusions: Genetic variation in the VDR is correlated with muscle strength, fat mass and bodyweight in premenopausal women. Further functional studies on the poly A microsatellite areneeded to elucidate whether this is the functionally relevant locus or if the polymorphism is in linkagedisequilibrium with a functional variant in a closely situated gene further downstream of the VDR30UTR.

  • 29.
    Grundberg, Elin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Lau, Edith M. C.
    Pastinen, Tomi
    Kindmark, Andreas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Nilsson, Olof
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Ljunggren, Östen
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Mellström, Dan
    Orwoll, Eric
    Redlund-Johnell, Inga
    Holmberg, Anna
    Gurd, Scott
    Leung, Ping Chung
    Kwok, Timothy
    Ohlsson, Claes
    Mallmin, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Brändström, Helena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Vitamin D receptor 3' haplotypes are unequally expressed in primary human bone cells and associated with increased fracture risk: the MrOS Study in Sweden and Hong Kong2007In: Journal of Bone and Mineral Research, ISSN 0884-0431, E-ISSN 1523-4681, Vol. 22, no 6, p. 832-840Article in journal (Refereed)
    Abstract [en]

    The VDR is a prime candidate gene for osteoporosis. Here, we studied three common VDR haplotypes in relation to bone phenotypes in 5014 participants of the global MrOS Study. We also studied the relative expression of the haplotypes in human bone cells. One haplotype was associated with increased fracture risk and differently expressed in primary human bone cells. Introduction: Vitamin D plays an essential role in skeletal metabolism by binding to its nuclear steroid receptor, the vitamin D receptor (VDR). The heritability of BMD is well established, and the VDR gene is considered a prime candidate suggested to partially account for genetically controlled BMD variance in the population. Materials and Methods: Here, we reconstructed common haplotypes in the VDR 3′ untranslated region (UTR) and studied the association to BMD and risk of vertebral fractures in elderly men from Sweden (n = 3014) and Hong Kong (n = 2000), all participants of the global MrOS Study. To assess any functional implications of the VDR polymorphisms, we studied allele-specific expressions of the different VDR 3′ UTR haplotypes in the normal chromosomal context of 70 unrelated human trabecular bone samples. This was performed by quantitative genotyping of coding polymorphisms in RNA samples and in corresponding DNA samples isolated from the bone samples. Results: Three major haplotypes were reconstructed and in agreement with the previously well-defined baT, BAt, and bAT haplotypes, herein denoted Hap1, Hap2, and Hap3. The Hap1 haplotype was independently associated with increased risk of vertebral fractures in Swedish men (OR, 1.655; 95% CI, 1.146-2.391; p < 0.01) and with lower lumbar spine BMD in elderly men from Sweden (p < 0.01) and Hong Kong (p < 0.05). The VDR gene was also shown to exhibit a 3′ UTR haplotype dependent allelic imbalance, indicating that the VDR Hap1 allele was overexpressed in human trabecular bone samples. Conclusions: The results indicate that the relatively overexpressed VDR Hap1 haplotype could be considered a risk allele for osteoporosis regardless of ethnicity.

  • 30.
    Grundberg, Elin
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
    Ribom, Eva L
    Department of Surgical Sciences.
    Brändström, Helena
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
    Ljunggren, Osten
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
    Mallmin, Hans
    Department of Surgical Sciences.
    Kindmark, Andreas
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
    A TA-repeat polymorphism in the gene for the estrogen receptor alpha does not correlate with muscle strength or body composition in young adult Swedish women.2005In: Maturitas, ISSN 0378-5122, Vol. 50, no 3, p. 153-60Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: There are conflicting data in the literature whether estrogens affect muscle strength. Prospective studies with hormone replacement therapy have not been able to convincingly demonstrate a muscular effect and the putative role of estrogen in the development of lean body mass is not established. Both lean mass and fat mass are known to be under strong genetic control and therefore we have investigated the relation between a TA-repeat in the gene for the estrogen receptor alpha (ERalpha) and muscle strength and body composition. METHODS: 175 healthy Swedish women, aged 20-39 were randomly selected from the population registry and included in the study. Body mass measurements (lean mass, fat mass, body weight and BMI) and muscle strength (quadriceps, hamstring and grip strength) were evaluated. The TA-repeat in the ERalpha gene was amplified by polymerase chain reaction. RESULTS: Alleles with a TA-repeat length of 16 repeats or shorter were denoted short (e), and repeat length of 17 repeats or longer were denoted long (E). Women homozygous for the short and long genotype were denoted ee (31%) and EE (21%), respectively, while heterozygous individuals were denoted Ee (48%). The frequencies were in Hardy-Weinberg equilibrium. No associations were found between ERalpha genotypes and muscle strength or body composition. CONCLUSION: The TA-repeat in the human ERalpha gene does not correlate with muscle strength or body mass measurements, indicating that body composition is not as sensitive to genetic variation in this receptor as other target organs for estrogen.

  • 31.
    Grundberg, Elin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Åkesson, Kristina
    Kindmark, Andreas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Gerdhem, Paul
    Holmberg, Anna
    Mellström, Dan
    Ljunggren, Östen
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Orwoll, Eric
    Mallmin, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Ohlsson, Claes
    Brändström, Helena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    The impact of estradiol on bone mineral density is modulated by the specific estrogen receptor-alpha cofactor retinoblastoma-interacting zinc finger protein-1 insertion/deletion polymorphism2007In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 92, no 6, p. 2300-2306Article in journal (Refereed)
    Abstract [en]

    Context: Estrogens regulate bone mass by binding to the estrogen receptor (ER)-α as well as ER-β. The specific ERα cofactor retinoblastoma-interacting zinc finger protein (RIZ)-1 enhances ERα function in the presence of estrogen. Objective: The objective of the study was to determine whether a RIZ P704 insertion (+)/deletion (-) (indel) polymorphism modulates the impact of estradiol on bone mineral density (BMD) and study the association between the polymorphism and BMD in elderly subjects. Design: This was a population-based, prospective, and crosssectional study, the Swedish MrOS Study, and the Malmö OPRA Study, respectively. Setting: The study was conducted at three academic medical centers: Sahlgrenska Academy in Gothenburg, Malmö University Hospital, and Uppsala University Hospital. Participants: In total, 4058 men and women, aged 69-81 yr, were randomly selected from population registries. Main Outcome Measures: BMD(grams per square centimeter) was measured at femoral neck, trochanter, lumbar spine, and total body. Results: The RIZ P704+/+ genotype was associated with low BMD in both women (femoral neck, P < 0.001; trochanter, P < 0.01; lumbar spine, P < 0.05; total body, P < 0.01) and men (lumbar spine, P < 0.05). However, the association between the polymorphism and BMD was dependent on estradiol status. The positive correlation between serum estradiol and BMD was significantly modulated by the genotype with a stronger correlation in the P704+/+ group than the P704-/- group (r = 0.19 vs. r = 0.08, P < 0.05). Conclusions: These large-scale studies of elderly men and women indicate that the ERα cofactor RIZ gene has a prominent effect on BMD, and the P704 genotype modulates the impact of estradiol on BMD. Further studies are required to determine whether this polymorphism modulates the estrogenic response to estradiol treatment.

  • 32. Hammarsten, Jan
    et al.
    Damber, J-E.
    Karlsson, M.
    Knutson, T.
    Ljunggren, Östen
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Ohlsson, C.
    Peeker, R.
    Smith, U.
    Mellström, D.
    Insulin and free oestradiol are independent risk factors for benign prostatic hyperplasia2009In: Prostate Cancer and Prostatic Diseases, ISSN 1365-7852, E-ISSN 1476-5608, Vol. 12, no 2, p. 160-165Article in journal (Refereed)
    Abstract [en]

    The aetiology of benign prostatic hyperplasia (BPH) remains unclear. The objective of the present study was to test the insulin, oestradiol and metabolic syndrome hypotheses as promoters of BPH. The design was a risk factor analysis of BPH in which the total prostate gland volume was related to endocrine and anthropometric factors. The participants studied were 184 representative men, aged 72-76 years, residing in Göteborg, Sweden. Using a multivariate analysis, BPH as measured by the total prostate gland volume correlated statistically significantly with fasting serum insulin (beta=0.200, P=0.028), free oestradiol (beta=0.233, P=0.008) and lean body mass (beta=0.257, P=0.034). Insulin and free oestradiol appear to be independent risk factors for BPH, confirming both the insulin and the oestradiol hypotheses. Our findings also seem to confirm the metabolic syndrome hypothesis. The metabolic syndrome and its major endocrine aberration, hyperinsulinaemia, are possible primary events in BPH.

  • 33.
    Harvey, N. C.
    et al.
    Univ Southampton, MRC Lifecourse Epidemiol Unit, Southampton SO16 6YD, Hants, England.;Univ Southampton, NIHR Southampton Biomed Res Ctr, Tremona Rd, Southampton, Hants, England.;Univ Hosp Southampton NHS Fdn Trust, Tremona Rd, Southampton, Hants, England..
    Johansson, H.
    Univ Gothenburg, CBAR, Sahlgrenska Acad, Gothenburg, Sweden.;Univ Sheffield, Sch Med, Ctr Metab Bone Dis, Beech Hill Rd, Sheffield S10 2RX, S Yorkshire, England..
    Oden, A.
    Univ Gothenburg, CBAR, Sahlgrenska Acad, Gothenburg, Sweden.;Univ Sheffield, Sch Med, Ctr Metab Bone Dis, Beech Hill Rd, Sheffield S10 2RX, S Yorkshire, England..
    Karlsson, M. K.
    Lund Univ, Dept Clin Sci Malmo, Clin & Mol Osteoporosis Res Unit, Malmo, Sweden.;Skane Univ Hosp, Dept Orthoped, Malmo, Sweden..
    Rosengren, B. E.
    Lund Univ, Dept Clin Sci Malmo, Clin & Mol Osteoporosis Res Unit, Malmo, Sweden.;Skane Univ Hosp, Dept Orthoped, Malmo, Sweden..
    Ljunggren, Östen
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology and mineral metabolism.
    Cooper, C.
    Univ Southampton, MRC Lifecourse Epidemiol Unit, Southampton SO16 6YD, Hants, England.;Univ Southampton, NIHR Southampton Biomed Res Ctr, Tremona Rd, Southampton, Hants, England.;Univ Hosp Southampton NHS Fdn Trust, Tremona Rd, Southampton, Hants, England.;Univ Oxford, NIHR Musculoskeletal Biomed Res Unit, Oxford, England..
    McCloskey, E.
    Univ Sheffield, Sch Med, Ctr Metab Bone Dis, Beech Hill Rd, Sheffield S10 2RX, S Yorkshire, England..
    Kanis, J. A.
    Univ Sheffield, Sch Med, Ctr Metab Bone Dis, Beech Hill Rd, Sheffield S10 2RX, S Yorkshire, England..
    Ohlsson, C.
    Univ Gothenburg, CBAR, Sahlgrenska Acad, Gothenburg, Sweden..
    Mellstrom, D.
    Univ Gothenburg, CBAR, Sahlgrenska Acad, Gothenburg, Sweden..
    FRAX predicts incident falls in elderly men: findings from MrOs Sweden2016In: Osteoporosis International, ISSN 0937-941X, E-ISSN 1433-2965, Vol. 27, no 1, p. 267-274Article in journal (Refereed)
    Abstract [en]

    A Summary Falls and fractures share several common risk factors. Although past falls is not included as an input variable in the FRAX calculator, we demonstrate that FRAX probability predicts risk of incident falls in the MrOs Sweden cohort. Introduction Although not included in the FRAXA (R) algorithm, it is possible that increased falls risk is partly dependent on other risk factors that are incorporated into FRAX. The aim of the present study was to determine whether fracture probability generated by FRAX might also predict risk of incident falls and the extent that a falls history would add value to FRAX. Methods We studied the relationship between FRAX probabilities and risk of falls in 1836 elderly men recruited to the MrOS study, a population-based prospective cohort of men from Sweden. Baseline data included falls history, clinical risk factors, bone mineral density (BMD) at femoral neck, and calculated FRAX probabilities. Incident falls were captured during an average of 1.8 years of follow-up. An extension of Poisson regression was used to investigate the relationship between FRAX, other risk variables, and the time-to-event hazard function of falls. All associations were adjusted for age and time since baseline. Results At enrolment, 15.5 % of the men had fallen during the preceding 12 months (past falls) and 39 % experienced one or more falls during follow-up (incident falls). The risk of incident falls increased with increasing FRAX probabilities at baseline (hazard ratio (HR) per standard deviation (SD), 1.16; 95 % confidence interval (95%CI), 1.06 to 1.26). The association between incident falls and FRAX probability remained after adjustment for past falls (HR per SD, 1.12; 95%CI, 1.03 to 1.22). High compared with low baseline FRAX score (>15 vs <15 % probability of major osteoporotic fracture) was strongly predictive of increased falls risk (HR, 1.64; 95%CI, 1.36 to 1.97) and remained stable with time. Whereas past falls were a significant predictor of incident falls (HR, 2.75; 95%CI, 2.32 to 3.25), even after adjustment for FRAX, the hazard ratio decreased markedly with increasing follow-up time. Conclusions Although falls are not included as an input variable, FRAX captures a component of risk for future falls and outperforms falls history with an extended follow-up time.

  • 34.
    Harvey, N. C.
    et al.
    Univ Oxford, Nuffield Dept Orthopaed Rheumatol & Musculoskelet, Botnar Res Ctr, Oxford, England..
    Oden, A.
    Univ Sheffield, Ctr Metab Bone Dis, Med Sch, Sheffield, S Yorkshire, England..
    Orwoll, E.
    Oregon Hlth & Sci Univ, Portland, OR 97201 USA..
    Lapidus, J.
    Oregon Hlth & Sci Univ, Dept Publ Hlth & Prevent Med, Div Biostat, Portland, OR 97201 USA..
    Kwok, T.
    Chinese Univ Hong Kong, Dept Med & Therapeut, Hong Kong, Hong Kong, Peoples R China.;Chinese Univ Hong Kong, Sch Publ Hlth, Hong Kong, Hong Kong, Peoples R China..
    Karlsson, M.
    Lund Univ, Dept Orthopaed & Clin Sci, Skane Univ Hosp, Malmo, Sweden..
    Rosengren, B.
    Lund Univ, Clin & Mol Osteoporosis Res Unit, Dept Clin Sci Malmo, Malmo, Sweden.;Skane Univ Hosp, Dept Orthoped, Malmo, Sweden..
    Ljunggren, Östen
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology and mineral metabolism.
    Cooper, C.
    Univ Oxford, Nuffield Dept Orthopaed Rheumatol & Musculoskelet, Botnar Res Ctr, Oxford, England..
    Kanis, J. A.
    Univ Sheffield, Ctr Metab Bone Dis, Med Sch, Sheffield, S Yorkshire, England..
    Ohlsson, C.
    Univ Gothenburg, Gothenburg, Sweden..
    Mellstrom, D.
    Univ Gothenberg, Sahlgrenska Acad, CBAR, Gothenburg, Sweden..
    Johansson, H.
    Univ Sheffield, Ctr Metab Bone Dis, Med Sch, Sheffield, S Yorkshire, England..
    McCloskey, E. V.
    Univ Sheffield, Ctr Metab Bone Dis, Med Sch, Sheffield, S Yorkshire, England..
    Mobility Related Risk Factors Predict Incident Fractures Independently Of Frax: The Osteoporotic Fractures In Men (MROS) Study2017In: Osteoporosis International, ISSN 0937-941X, E-ISSN 1433-2965, Vol. 28, p. S61-S61Article in journal (Other academic)
  • 35.
    Harvey, N. C.
    et al.
    Univ Oxford, Musculoskeletal Epidemiol, Botnar Res Ctr, Nuffield Dept Orthopaed Rheumatol & Musculoskelet, Oxford, England..
    Oden, A.
    Univ Sheffield, Sch Med, Ctr Metab Bone Dis, Sheffield, S Yorkshire, England..
    Orwoll, E.
    Oregon Hlth & Sci Univ, Portland, OR 97201 USA..
    Lapidus, J.
    Oregon Hlth & Sci Univ, Dept Publ Hlth & Prevent Med, Div Biostat, Portland, OR 97201 USA..
    Kwok, T.
    Chinese Univ Hong Kong, Dept Med & Therapeut, Hong Kong, Hong Kong, Peoples R China.;Chinese Univ Hong Kong, Sch Publ Hlth, Hong Kong, Hong Kong, Peoples R China..
    Karlsson, M.
    Lund Univ, Dept Orthopaed & Clin Sci, Skane Univ Hosp, Malmo, Sweden..
    Rosengren, B.
    Lund Univ, Clin & Mol Osteoporosis Res Unit, Dept Clin Sci Malmo, Malmo, Sweden.;Skane Univ Hosp, Dept Orthoped, Malmo, Sweden..
    Ljunggren, Östen
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology and mineral metabolism.
    Cooper, C.
    Univ Oxford, Musculoskeletal Epidemiol, Botnar Res Ctr, Nuffield Dept Orthopaed Rheumatol & Musculoskelet, Oxford, England..
    McCloskey, E.
    Univ Sheffield, Sch Med, Ctr Metab Bone Dis, Sheffield, S Yorkshire, England..
    Kanis, J. A.
    Univ Sheffield, Sch Med, Ctr Metab Bone Dis, Sheffield, S Yorkshire, England..
    Ohlsson, C.
    Univ Gothenburg, Gothenburg, Sweden..
    Mellstrom, D.
    Univ Gothenberg, CBAR, Sahlgrenska Acad, Gothenburg, Sweden..
    Johansson, H.
    Univ Sheffield, Sch Med, Ctr Metab Bone Dis, Sheffield, S Yorkshire, England..
    PRIOR FALLS PREDICT INCIDENT FRACTURES INDEPENDENTLY OF FRAX: The Osteoporotic Fractures In Men (MROS) Study2017In: Osteoporosis International, ISSN 0937-941X, E-ISSN 1433-2965, Vol. 28, p. S259-S259Article in journal (Other academic)
  • 36.
    Harvey, Nicholas C.
    et al.
    Univ Southampton, MRC Lifecourse Epidemiol Unit, Southampton SO16 6YD, Hants, England.;Univ Southampton, NIHR Southampton Biomed Res Ctr, Southampton, Hants, England.;Univ Hosp Southampton NHS Fdn Trust, Southampton, Hants, England..
    Oden, Anders
    Univ Gothenburg, Sahlgrenska Acad, CBAR, Gothenburg, Sweden.;Univ Sheffield, Ctr Metab Bone Dis, Sheffield, S Yorkshire, England..
    Orwoll, Eric
    Oregon Hlth & Sci Univ, Portland, OR 97201 USA..
    Lapidus, Jodi
    Oregon Hlth & Sci Univ, Div Biostat, Dept Publ Hlth & Prevent Med, Portland, OR 97201 USA..
    Kwok, Timothy
    Chinese Univ Hong Kong, Dept Med & Therapeut, Hong Kong, Hong Kong, Peoples R China.;Chinese Univ Hong Kong, Sch Publ Hlth, Hong Kong, Hong Kong, Peoples R China..
    Karlsson, Magnus K.
    Lund Univ, Clin & Mol Osteoporosis Res Unit, Dept Clin Sci Malmo, Malmo, Sweden.;Skane Univ Hosp, Dept Orthoped, Malmo, Sweden..
    Rosengren, Björn E.
    Lund Univ, Clin & Mol Osteoporosis Res Unit, Dept Clin Sci Malmo, Malmo, Sweden.;Skane Univ Hosp, Dept Orthoped, Malmo, Sweden..
    Ljunggren, Östen
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology and mineral metabolism.
    Cooper, Cyrus
    Univ Southampton, MRC Lifecourse Epidemiol Unit, Southampton SO16 6YD, Hants, England.;Univ Southampton, NIHR Southampton Biomed Res Ctr, Southampton, Hants, England.;Univ Hosp Southampton NHS Fdn Trust, Southampton, Hants, England.;Univ Oxford, NIHR Oxford Biomed Res Ctr, Oxford, England..
    McCloskey, Eugene
    Univ Sheffield, Ctr Metab Bone Dis, Sheffield, S Yorkshire, England.;Univ Sheffield, Ctr Integrated Res Musculoskeletal Ageing CIMA, Mellanby Ctr Bone Res, Sheffield, S Yorkshire, England..
    Kanis, John A.
    Univ Sheffield, Ctr Metab Bone Dis, Sheffield, S Yorkshire, England.;Catholic Univ Australia, Inst Hlth & Aging, Melbourne, Vic, Australia..
    Ohlsson, Claes
    Univ Gothenburg, Sahlgrenska Acad, CBAR, Gothenburg, Sweden..
    Mellström, Dan
    Univ Gothenburg, Sahlgrenska Acad, CBAR, Gothenburg, Sweden..
    Johansson, Helena
    Univ Gothenburg, Sahlgrenska Acad, CBAR, Gothenburg, Sweden.;Univ Sheffield, Ctr Metab Bone Dis, Sheffield, S Yorkshire, England.;Catholic Univ Australia, Inst Hlth & Aging, Melbourne, Vic, Australia..
    Falls Predict Fractures Independently of FRAX Probability: A Meta-Analysis of the Osteoporotic Fractures in Men (MrOS) Study2018In: Journal of Bone and Mineral Research, ISSN 0884-0431, E-ISSN 1523-4681, Vol. 33, no 3, p. 510-516Article in journal (Refereed)
    Abstract [en]

    Although prior falls are a well-established predictor of future fracture, there is currently limited evidence regarding the specific value of falls history in fracture risk assessment relative to that of other clinical risk factors and bone mineral density (BMD) measurement. We therefore investigated, across the three Osteoporotic Fractures in Men (MrOS) Study cohorts, whether past falls predicted future fracture independently of FRAX and whether these associations varied with age and follow-up time. Elderly men were recruited from MrOS Sweden, Hong Kong, and USA. Baseline data included falls history (over the preceding 12 months), clinical risk factors, BMD at femoral neck, and calculated FRAX probabilities. An extension of Poisson regression was used to investigate the associations between falls, FRAX probability, and incident fracture, adjusting for age, time since baseline, and cohort in base models; further models were used to investigate interactions with age and follow-up time. Random-effects meta-analysis was used to synthesize the individual country associations. Information on falls and FRAX probability was available for 4365 men in USA (mean age 73.5 years; mean follow-up 10.8 years), 1823 men in Sweden (mean age 75.4 years; mean follow-up 8.7 years), and 1669 men in Hong Kong (mean age 72.4 years; mean follow-up 9.8 years). Rates of past falls were similar at 20%, 16%, and 15%, respectively. Across all cohorts, past falls predicted incident fracture at any site (hazard ratio [HR]=1.69; 95% confidence interval [CI] 1.49, 1.90), major osteoporotic fracture (MOF) (HR=1.56; 95% CI 1.33, 1.83), and hip fracture (HR=1.61; 95% CI 1.27, 2.05). Relationships between past falls and incident fracture remained robust after adjustment for FRAX probability: adjusted HR (95% CI) any fracture: 1.63 (1.45, 1.83); MOF: 1.51 (1.32, 1.73); and hip: 1.54 (1.21, 1.95). In conclusion, past falls predicted incident fracture independently of FRAX probability, confirming the potential value of falls history in fracture risk assessment.

  • 37.
    Holgersson, Magdalena Bentmar
    et al.
    Lund Univ, Dept Translat Med, Jan Waldenstroms Gata 35,Bldg 91,Plan 10, S-20502 Malmo, Sweden..
    Ruhayel, Yasir
    Skane Univ Hosp, Dept Urol, Malmo, Sweden..
    Karlsson, Magnus
    Lund Univ, Dept Orthoped & Clin Sci, Malmo, Sweden..
    Giwercman, Aleksander
    Lund Univ, Dept Translat Med, Jan Waldenstroms Gata 35,Bldg 91,Plan 10, S-20502 Malmo, Sweden..
    Bjartell, Anders
    Lund Univ, Dept Translat Med, Jan Waldenstroms Gata 35,Bldg 91,Plan 10, S-20502 Malmo, Sweden.;Skane Univ Hosp, Dept Urol, Malmo, Sweden..
    Ohlsson, Claes
    Gothenburg Univ, Sahlgrenska Acad, Ctr Bone & Arthrit Res, Dept Internal Med & Clin Nutr, Gothenburg, Sweden.;Gothenburg Univ, Sahlgrenska Acad, Ctr Bone & Arthrit Res, Dept Geriatr, Gothenburg, Sweden..
    Mellstrom, Dan
    Gothenburg Univ, Sahlgrenska Acad, Ctr Bone & Arthrit Res, Dept Internal Med & Clin Nutr, Gothenburg, Sweden.;Gothenburg Univ, Sahlgrenska Acad, Ctr Bone & Arthrit Res, Dept Geriatr, Gothenburg, Sweden..
    Ljunggren, Östen
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology and mineral metabolism.
    Haghsheno, Mohammad-Ali
    Univ Gothenburg, Sahlgrenska Acad, Inst Clin Sci, Dept Urol,Sahlgrenska Canc Ctr, Gothenburg, Sweden..
    Damber, Jan-Erik
    Univ Gothenburg, Sahlgrenska Acad, Inst Clin Sci, Dept Urol,Sahlgrenska Canc Ctr, Gothenburg, Sweden..
    Giwercman, Yvonne Lundberg
    Lund Univ, Dept Translat Med, Jan Waldenstroms Gata 35,Bldg 91,Plan 10, S-20502 Malmo, Sweden..
    Lower prostate cancer risk in Swedish men with the androgen receptor E213 A-allele2017In: Cancer Causes and Control, ISSN 0957-5243, E-ISSN 1573-7225, Vol. 28, no 3, p. 227-233Article in journal (Refereed)
    Abstract [en]

    In a previous population-based study on 3369 European men with self-reported prostate cancer (PCa), it was shown that androgen receptor (AR) haplotype designated H2 was associated with high levels of serum PSA (prostate-specific antigen) concentration, and, at the same time, with low risk for PCa. The aim of this study was to replicate this finding in other cohorts, with registry-based cancer diagnosis. Using data from two population-based cohorts; the Malmo Diet and Cancer Study (MDCS, n = 12,121) and the Swedish Osteoporotic fractures in men study (MrOS, n = 1,120), 628 men with PCa and 1,374 controls were identified and genotyped. PCa data were collected from the Swedish national cancer registry. PCa odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for carriers of the particular AR haplotype, tagged by the rs6624304 T-allele. The 15% of men who were carriers of the AR haplotype H2 had approximately one-third lower risk for PCa diagnosis compared to those with the most common H1 variant (OR 0.65; 95% CI 0.45-0.94; p = 0.021). The same trend, although not statistically significant (OR 0.75; 95% CI 0.47-1.24; p = 0.275), was observed in MrOS Sweden. When both cohorts were merged, an even more significant result was observed (OR 0.68; 95% CI 0.51-0.90; p = 0.008). Swedish men with the variant AR haplotype H2, tagged by rs6624304, have significantly lower risk of PCa compared to those with the more common variant.

  • 38.
    Holmlund-Suila, Elisa
    et al.
    Univ Helsinki, Childrens Hosp, Helsinki, Finland.;Helsinki Univ Hosp, Helsinki, Finland..
    Viljakainen, Heli
    Univ Helsinki, Childrens Hosp, Helsinki, Finland.;Helsinki Univ Hosp, Helsinki, Finland.;Folkhalsan Res Ctr, Helsinki, Finland..
    Ljunggren, Östen
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology and mineral metabolism.
    Hytinantti, Timo
    Helsinki Matern Hosp, Helsinki, Finland..
    Andersson, Sture
    Univ Helsinki, Childrens Hosp, Helsinki, Finland.;Helsinki Univ Hosp, Helsinki, Finland..
    Makitie, Outi
    Univ Helsinki, Childrens Hosp, Helsinki, Finland.;Helsinki Univ Hosp, Helsinki, Finland.;Folkhalsan Res Ctr, Helsinki, Finland.;Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden.;Karolinska Inst, Ctr Mol Med, Stockholm, Sweden.;Karolinska Univ Hosp, Dept Clin Genet, Stockholm, Sweden..
    Fibroblast Growth Factor 23 Concentrations Reflect Sex Differences in Mineral Metabolism and Growth in Early Infancy2016In: Hormone Research in Paediatrics, ISSN 1663-2818, E-ISSN 1663-2826, Vol. 85, no 4, p. 232-241Article in journal (Refereed)
    Abstract [en]

    Background: The role of fibroblast growth factor 23 (FGF23) in the regulation of mineral homeostasis in early life is inadequately understood. We aimed to explore the effects of vitamin D supplementation on serum FGF23 and to elucidate longitudinal changes in FGF23, in addition to studying its association with mineral metabolism in early infancy. Methods: Altogether 113 healthy infants received vitamin D 3 10, 30 or 40 mu g/day from age 0.5 to 3.0 months. Cord blood at birth and capillary blood samples at 3 months were analyzed for serum 25-hydroxyvitamin D, parathyroid hormone, phosphate, calcium and intact and C-terminal FGF23. Results: In repeated-measures ANCOVA, intact FGF23 concentration increased with time (p < 0.001) and C-terminal FGF23 decreased (p < 0.001). At 3 months, girls had a higher concentration of intact FGF23 (51 vs. 26 pg/ml, p < 0.001) and a greater increase over time (Delta FGF23 intact 45 vs. 16 pg/ml, p = 0.001) than boys. Vitamin D did not affect serum intact or C-terminal FGF23 concentrations. Girls showed a positive correlation between phosphate and intact FGF23 (p = 0.004), whereas in boys phosphate and C-terminal FGF23 correlated inversely (p = 0.006). Conclusions: A substantial sex-related difference in intact FGF23 concentration exists during early infancy, possibly related to differences in skeletal growth between boys and girls. (C) 2016 S. Karger AG, Basel

  • 39. Jakob, F.
    et al.
    Oertel, H.
    Langdahl, B.
    Ljunggren, Östen
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Barrett, A.
    Karras, D.
    Walsh, J. B.
    Fahrleitner-Pammer, A.
    Rajzbaum, G.
    Barker, C.
    Lems, W. F.
    Marin, F.
    Effects of teriparatide in postmenopausal women with osteoporosis pre-treated with bisphosphonates: 36-month results from the European Forsteo Observational Study2012In: European Journal of Endocrinology, ISSN 0804-4643, E-ISSN 1479-683X, Vol. 166, no 1, p. 87-97Article in journal (Refereed)
    Abstract [en]

    Objectives: To describe fracture rates, back pain, and health-related quality of life (HRQoL) in postmenopausal women with osteoporosis and prior bisphosphonate therapy, treated with teriparatide for up to 18 months and followed up for a further 18 months.

    Design: Prospective, multinational, and observational study.

    Methods: Data on prior bisphosphonate use, clinical fractures, back pain visual analog scale (VAS), and HRQoL (EQ-5D) were collected over 36 months. Fracture data were summarized in 6-month intervals and analyzed using logistic regression with repeated measures. Changes from baseline in back pain VAS and EQ-VAS were analyzed using a repeated measures model.

    Results: Of the 1581 enrolled patients with follow-up data, 1161 (73.4%) had a history of prior bisphosphonate use (median duration: 36 months). Of them, 169 (14.6%) sustained >= 1 fracture during 36-month follow-up. Adjusted odds of fracture were significantly decreased at each 6-month interval compared with the first 6 months of teriparatide treatment: 37% decrease in the 12 to ! 18 months period during teriparatide treatment (P=0.03) and a 76% decrease in the 12- to 18-month period after teriparatide was discontinued (P<0.001). Significant reductions in back pain and improvement in HRQoL were observed.

    Conclusions: Postmenopausal women with severe osteoporosis previously treated with bisphosphonates had a significant reduction in the incidence of fractures compared with the first 6 months of therapy, a reduction in back pain and an improvement in HRQoL during up to 18 months of teriparatide treatment. These outcomes were still evident for at least 18 months after teriparatide was discontinued. The results should be interpreted in the context of an uncontrolled, observational study in a routine clinical setting.

  • 40. Johansson, H.
    et al.
    Oden, A.
    Kanis, J.
    McCloskey, E.
    Lorentzon, M.
    Ljunggren, Östen
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Karlsson, M. K.
    Thorsby, P. M.
    Tivesten, A.
    Barrett-Connor, E.
    Ohlsson, C.
    Mellstrom, D.
    Low serum vitamin D is associated with increased mortality in elderly men: MrOS Sweden2012In: Osteoporosis International, ISSN 0937-941X, E-ISSN 1433-2965, Vol. 23, no 3, p. 991-999Article in journal (Refereed)
    Abstract [en]

    In elderly man, low serum 25-hydroxyvitamin D (25(OH)D) was associated with a substantial excess risk of death compared to 25(OH)D values greater than 50-70 nmol/l, but the association attenuated with time. The aim of the present study was to determine whether poor vitamin D status was associated with an increase in the risk of death in elderly men. We studied the relationship between serum 25(OH)D and the risk of death in 2,878 elderly men drawn from the population and recruited to the MrOS study in Sweden. Baseline data included general health and lifestyle measures and serum 25(OH)D measured by competitive RIA. Men were followed for up to 8.2 years (average 6.0 years). Mortality adjusted for comorbidities decreased by 5% for each SD increase in 25(OH)D overall (gradient of risk 1.05; 95% confidence interval 0.96-1.14). The predictive value of 25(OH)D for death was greatest below a threshold value of 50-70 nmol/l, was greatest at approximately 3 years after baseline and thereafter decreased with time. Low serum 25(OH)D is associated with a substantial excess risk of death compared to 25(OH)D values greater than 50-70 nmol/l, but the association attenuates with time. These findings, if causally related, have important implications for intervention in elderly men.

  • 41.
    Johansson, H.
    et al.
    Univ Sheffield, Sch Med, Ctr Metab Bone Dis, Sheffield, S Yorkshire, England..
    Oden, A.
    Univ Sheffield, Sch Med, Ctr Metab Bone Dis, Sheffield, S Yorkshire, England..
    Karlsson, M.
    Lund Univ, Skane Univ Hosp, Dept Orthopaed & Clin Sci, Malmo, Sweden..
    Lorentzon, M.
    Sahlgrens Acad, Inst Med, Dept Internal Med & Clin Nutr, Geriatr Med, Molndal, Sweden..
    Kanis, J. A.
    Univ Sheffield, Sch Med, Ctr Metab Bone Dis, Sheffield, S Yorkshire, England..
    Rosengren, B.
    Lund Univ, Dept Clin Sci Malmo, Clin & Mol Osteoporosis Res Unit, Malmo, Sweden.;Skane Univ Hosp, Dept Orthoped, Malmo, Sweden..
    Mellström, D.
    Sahlgrens Acad, Inst Med, Dept Internal Med & Clin Nutr, Geriatr Med, Molndal, Sweden..
    Ljunggren, Östen
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology and mineral metabolism.
    OhIsson, C.
    Univ Gothenburg, Gothenburg, Sweden..
    Harvey, N. C.
    Univ Southampton, MRC Lifecourse Epidemiol Unit, Southampton, Hants, England..
    McCloskey, E.
    Univ Sheffield, Sch Med, Ctr Metab Bone Dis, Sheffield, S Yorkshire, England..
    Femoral Neck BMD Is Still The Preferred Site In The Assessment Of Hip Fracture In Elderly Men (10-Year Follow-Up Of MROS Sweden)2016In: Osteoporosis International, ISSN 0937-941X, E-ISSN 1433-2965, Vol. 27, p. S58-S59Article in journal (Other academic)
  • 42. Johansson, H.
    et al.
    Oden, A.
    Lerner, U. H.
    Jutberger, H.
    Lorentzon, M.
    Barrett-Connor, E.
    Karlsson, M. K.
    Ljunggren, Östen
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Metabolic Bone Diseases.
    Smith, U.
    McCloskey, E.
    Kanis, J. A.
    Ohlsson, C.
    Mellström, D.
    High serum adiponectin predicts incident fractures in elderly men: MrOS Sweden2012In: Osteoporosis International, ISSN 0937-941X, E-ISSN 1433-2965, Vol. 23, no 2, p. S306-S307Article in journal (Other academic)
  • 43. Johansson, Helena
    et al.
    Oden, Anders
    Karlsson, Magnus
    Ljunggren, Östen
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology and mineral metabolism.
    Mccloskey, Eugene
    Kanis, John A.
    Ohlsson, Claes
    Mellstrom, Dan
    Adiponectin and 10-year probability of fracture in elderly men: MR OS Sweden2013In: Osteoporosis International, ISSN 0937-941X, E-ISSN 1433-2965, Vol. 24, no Suppl. 1, p. S47-S47Article in journal (Other academic)
  • 44. Johansson, Helena
    et al.
    Oden, Anders
    Lerner, Ulf H.
    Jutberger, Hans
    Lorentzon, Mattias
    Barrett-Connor, Elizabeth
    Karlsson, Magnus K.
    Ljunggren, Östen
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Smith, Ulf
    McCloskey, Eugene
    Kanis, John A.
    Ohlsson, Claes
    Mellstrom, Dan
    High serum adiponectin predicts incident fractures in elderly men: Osteoporotic fractures in men (MrOS) Sweden2012In: Journal of Bone and Mineral Research, ISSN 0884-0431, E-ISSN 1523-4681, Vol. 27, no 6, p. 1390-1396Article in journal (Refereed)
    Abstract [en]

    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.

  • 45.
    Jonsson, E.
    et al.
    Quantify Res, Stockholm, Sweden..
    Hansson-Hedblom, A.
    Quantify Res, Stockholm, Sweden..
    Ljunggren, Östen
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology and mineral metabolism.
    Akesson, K.
    Lund Univ, Dept Clin Sci, Clin & Mol Osteoporosis Unit, Malmo, Sweden..
    Spangeus, A.
    Linkoping Univ, Dept Med & Hlth Sci, Linkoping, Sweden..
    Borgstrom, F.
    Quantify Res, Stockholm, Sweden.;Karolinska Inst, Stockholm, Sweden..
    Kanis, J. A.
    Catholic Univ Australian, Melbourne, Vic, Australia.;Univ Sheffield, Sheffield, S Yorkshire, England..
    Cost-Effectiveness Of Complying With Treatment Guidelines In Sweden2017In: Osteoporosis International, ISSN 0937-941X, E-ISSN 1433-2965, Vol. 28, p. S440-S440Article in journal (Other academic)
  • 46.
    Jonsson, E.
    et al.
    Quantify Res, Hantverkargatan 8, SE-11221 Stockholm, Sweden..
    Hansson-Hedblom, A.
    Quantify Res, Hantverkargatan 8, SE-11221 Stockholm, Sweden..
    Ljunggren, Östen
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology and mineral metabolism.
    Akesson, K.
    Lund Univ, Dept Clin Sci, Clin & Mol Osteoporosis Unit, Malmo, Sweden..
    Spangeus, A.
    Linkoping Univ, Dept Endocrinol Med & Hlth, Linkoping, Sweden..
    Kanis, J. A.
    Univ Sheffield, Sheffield, S Yorkshire, England.;Catholic Univ Australia, Melbourne, Vic, Australia..
    Borgstrom, F.
    Quantify Res, Hantverkargatan 8, SE-11221 Stockholm, Sweden.;Karolinska Inst, LIME MMC, Stockholm, Sweden..
    A health economic simulation model for the clinical management of osteoporosis2018In: Osteoporosis International, ISSN 0937-941X, E-ISSN 1433-2965, Vol. 29, no 3, p. 545-555Article in journal (Refereed)
    Abstract [en]

    The objective was to estimate the burden of osteoporosis in Sweden based on current clinical practice and the cost-effectiveness of improvements in the management of osteoporosis over the clinical management compared to current clinical practice. Results showed that better compliance to treatment guidelines is associated with better projected outcomes and cost-savings.

    Introduction

    The purpose of this study is to estimate the burden of osteoporosis in Sweden based on current clinical practice and the cost-effectiveness of improvements in the management of osteoporosis over the clinical management compared to current clinical practice.

    Methods

    The analysis was carried out using a model that simulates the individual patients considered for pharmacological treatment during 1 year and their projected osteoporosis treatment pathway, quality-adjusted life years (QALYs) and costs over their remaining lifetime. All patients regardless of treatment or no treatment were simulated. Information on current management of osteoporosis in terms of patient characteristics and treatment patterns were derived from a Swedish osteoporosis research database based on national registers and patient records. Current (standard) clinical management was compared with alternative scenarios mirroring Swedish treatment guidelines.

    Results

    The national burden in terms of lost QALYs was estimated at 14,993 QALYs and the total economic cost at €776M. Scenario analyses showed that 382–3864 QALYs could be gained at a cost/QALY ranging from cost-saving to €31368, depending on the scenario. The margin of investment, i.e. the maximum amount that could be invested in the healthcare system to achieve these improvements up to the limit of the willingness to pay/QALY, was estimated at €199M on a population level (€3,634/patient).

    Conclusions

    The analysis showed that better compliance to treatment guidelines is associated with better projected outcomes and cost-savings. From a cost-effectiveness perspective, there is also considerable room for investment to achieve these improvements in the management of osteoporosis.

  • 47.
    Jonsson, E.
    et al.
    Quantify Res, Stockholm, Sweden..
    Strom, O.
    Quantify Res, Stockholm, Sweden.;Karolinska Inst, LIME MMC, Stockholm, Sweden..
    Spangeus, A.
    Linkoping Univ Hosp, Linkoping, Sweden..
    Akesson, K.
    Lund Univ, Skane Univ Hosp, Malmo, Sweden..
    Ljunggren, Östen
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology and mineral metabolism.
    Borgstrom, R.
    Quantify Res, Stockholm, Sweden.;Karolinska Inst, LIME MMC, Stockholm, Sweden..
    Banefelt, J.
    Quantify Res, Stockholm, Sweden..
    Toth, E.
    UCB Pharma, Brussels, Belgium..
    Libanati, C.
    UCB Pharma, Brussels, Belgium..
    Charokopou, M.
    UCB Pharma, Brussels, Belgium..
    Risk Of Major Osteoporotic Fracture (Hip, Vertebral, Radius, Humerus [Mof]) After First, Second And Third Fragility Fracture In A Swedish General Population Cohort2017In: Value in Health, ISSN 1098-3015, E-ISSN 1524-4733, Vol. 20, no 9, p. A528-A528Article in journal (Other academic)
  • 48.
    Jonsson, Emma
    et al.
    Quantify Res, Hantverkargatan 8, S-11221 Stockholm, Sweden..
    Eriksson, Daniel
    Quantify Res, Hantverkargatan 8, S-11221 Stockholm, Sweden..
    Åkesson, Kristina
    Skane Univ Hosp, Dept Orthopaed, Malmo, Sweden..
    Ljunggren, Östen
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology and mineral metabolism.
    Salomonsson, Stina
    Karolinska Inst, Ctr Mol Med, Stockholm, Sweden.;Merck Sharp & Dohme Sweden, Sollentuna, Sweden..
    Borgström, Fredrik
    Quantify Res, Hantverkargatan 8, S-11221 Stockholm, Sweden.;Karolinska Inst, LIME MMC, Stockholm, Sweden..
    Ström, Oskar
    Quantify Res, Hantverkargatan 8, S-11221 Stockholm, Sweden..
    Swedish osteoporosis care2015In: ARCHIVES OF OSTEOPOROSIS, ISSN 1862-3522, Vol. 10, no 1, article id 24Article in journal (Refereed)
    Abstract [en]

    Mini-abstract The objective of this study was to review and describe the current state of Swedish osteoporosis care and to highlight ongoing challenges. This report encompasses quantitative health outcomes based on Swedish registry data as well as organizational and management aspects. Executive summary Swedish osteoporosis care is characterized by a significant burden of disease, difficulties in identifying high-risk patients, and fragmented pathways for patients in need of secondary fracture prevention. This report aimed to describe the current state, gaps, and challenges in Swedish osteoporosis care, using Swedish national databases, questionnaires, and interviews with healthcare representatives. A secondary aim was to develop quality and process measures to compare differences between counties and to use those measures to describe the interaction between quantitative health outcomes and aspects of care organization and management. In conjunction with fractures, a considerably smaller proportion of men are treated than women, and a smaller proportion of older women are treated compared to younger groups. Between 3 and 16 % of patients receive treatment after a fracture, and the treatment rate in this patient group can likely increase. In addition to an unsatisfactory treatment rate, a limited number of those treated continue treatment throughout the recommended treatment durations, leading to increased risk of fracture. With a substantial variation between counties, there is a clear difficulty to identify non-persistent patients and switch to an alternative treatment. Collaboration around the patient across specialties has been lacking, and systems for secondary prevention have been concentrated to a few counties. However, when this study was conducted, there was a general trend towards implementing regional care programs. This report suggests possible strategies for improving quality of care and, hopefully, it can provide a basis for future evaluations and regional improvement of osteoporosis care in Sweden and other countries.

  • 49. Jutberger, Hans
    et al.
    Lorentzon, Mattias
    Barrett-Connor, Elizabeth
    Johansson, Helena
    Kanis, John A.
    Ljunggren, Östen
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Karlsson, Magnus K.
    Rosengren, Björn E.
    Redlund-Johnell, Inga
    Orwoll, Eric
    Ohlsson, Claes
    Mellström, Dan
    Smoking Predicts Incident Fractures in Elderly Men: Mr OS Sweden2010In: Journal of Bone and Mineral Research, ISSN 0884-0431, E-ISSN 1523-4681, Vol. 25, no 5, p. 1010-1016Article in journal (Refereed)
    Abstract [en]

    The aim of the present study was to investigate the association between smoking and BMD, radiographically verified prevalent vertebral fractures and incident fractures in elderly men. At baseline 3003 men, aged 69 - 80 years old from the Swedish Mr Os study, completed a standard questionnaire concerning smoking habits and had BMD of the hip and spine measured using DXA; 1412 men had an X-ray of the thoracic-/lumbar spine. Radiological registers were used to confirm reported new fractures after the baseline visit. At baseline 8.4 % were current smokers. Current smokers had 6.2 % lower BMD at the total hip and 5.4 % at the lumbar spine (p<0.001). Current smoking remained independently, inversely associated with BMD at the hip and lumbar spine after adjusting for age, height, weight, calcium intake, physical activity and centres as co-variates. Prevalent vertebral fractures among current smokers were increased in unadjusted analyses (OR 1.90; 95% CI: 1.26-2.87) and after adjustment for lumbar BMD (OR 1.67; 1.09-2.55). Smokers had a high risk for two or more prevalent vertebral fractures (OR 3.18; 1.88-5.36). During the average follow-up of 3.3 years, 209 men sustained an X-ray verified fracture. Incident fracture risk among smokers was calculated with Cox proportional hazard models. Current smokers had increased risk of all new fractures (HR 1.76; 1.19-2.61), non-vertebral osteoporotic fractures defined as humerus, radius, pelvis and hip fractures (HR 2.14; 1.18-3.88), clinical and X-ray verified vertebral fractures (HR 2.53; 1.37-4.65) as well as of hip fracture (HR 3.16; 1.44-6.95). After adjustment for BMD, including other co-variates, no significant association between smoking and incident fractures was found. Current tobacco smoking in elderly men is associated with low BMD, prevalent vertebral fractures and incident fractures, especially vertebral and hip fractures.

  • 50. Karlsson, Magnus K
    et al.
    Ribom, Eva L
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Nilsson, J-Å
    Karlsson, Caroline
    Cöster, Maria
    Vonschewelov, Thord
    Mallmin, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Ljunggren, Östen
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology and mineral metabolism.
    Ohlsson, Claes
    Mellström, Dan
    Lorentzon, Mattias
    Leung, P C
    Lau, Edith
    Cauley, Jane A
    Barrett-Connor, Elizabeth
    Stefanick, Marcia L
    Orwoll, Eric
    Rosengren, Björn E
    International and ethnic variability of falls in older men2014In: Scandinavian Journal of Public Health, ISSN 1403-4948, E-ISSN 1651-1905, Vol. 42, no 2, p. 194-200Article in journal (Refereed)
    Abstract [en]

    Aims: Fallers and especially recurrent fallers are at high risk for injuries. The aim of this study was to evaluate fall epidemiology in older men with special attention to the influence of age, ethnicity and country of residence. Methods: 10,998 men aged 65 years or above recruited in Hong Kong, the United States (US) and Sweden were evaluated in a cross-sectional retrospective study design. Self-reported falls and fractures for the preceding 12 months were registered through questionnaires. Group comparisons were done by chi-square test or logistic regression. Results: The proportion of fallers among the total population was 16.5% in ages 65-69, 24.8% in ages 80-84 and 43.2% in ages above 90 (P <0.001). The corresponding proportions of recurrent fallers in the same age groups were 6.3%, 10.1% and 18.2%, respectively (P <0.001), and fallers with fractures 1.0%, 2.3% and 9.1%, respectively (P <0.001). The proportion of fallers was highest in the US, intermediate in Sweden and lowest in Hong Kong (in most age groups P <0.05). The proportion of fallers among white men in the US was higher than in white men in Sweden (all comparable age groups P <0.01) but there were no differences in the proportion of fallers in US men with different ethnicity. Conclusions: The proportion of fallers in older men is different in different countries, and data in this study corroborate with the view that society of residence influences fall prevalence more than ethnicity.

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