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Ljunggren, Östen
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Publications (10 of 134) Show all publications
Jonsson, E., Hansson-Hedblom, A., Ljunggren, Ö., Akesson, K., Spangeus, A., Kanis, J. A. & Borgstrom, F. (2018). A health economic simulation model for the clinical management of osteoporosis. Osteoporosis International, 29(3), 545-555
Open this publication in new window or tab >>A health economic simulation model for the clinical management of osteoporosis
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2018 (English)In: Osteoporosis International, ISSN 0937-941X, E-ISSN 1433-2965, Vol. 29, no 3, p. 545-555Article in journal (Refereed) Published
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.

Keywords
Cost, Fracture, Osteoporosis, Quality-of-life, Register, Sweden
National Category
Health Care Service and Management, Health Policy and Services and Health Economy Clinical Medicine
Identifiers
urn:nbn:se:uu:diva-351263 (URN)10.1007/s00198-017-4325-4 (DOI)000426646900003 ()29196775 (PubMedID)
Available from: 2018-06-11 Created: 2018-06-11 Last updated: 2018-06-11Bibliographically approved
Harvey, N. C., Oden, A., Orwoll, E., Lapidus, J., Kwok, T., Karlsson, M. K., . . . Johansson, H. (2018). Falls Predict Fractures Independently of FRAX Probability: A Meta-Analysis of the Osteoporotic Fractures in Men (MrOS) Study. Journal of Bone and Mineral Research, 33(3), 510-516
Open this publication in new window or tab >>Falls Predict Fractures Independently of FRAX Probability: A Meta-Analysis of the Osteoporotic Fractures in Men (MrOS) Study
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2018 (English)In: Journal of Bone and Mineral Research, ISSN 0884-0431, E-ISSN 1523-4681, Vol. 33, no 3, p. 510-516Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
WILEY, 2018
Keywords
OSTEOPOROSIS, EPIDEMIOLOGY, FRAX, FALLS, FRACTURE, INTERACTION
National Category
Orthopaedics Endocrinology and Diabetes
Identifiers
urn:nbn:se:uu:diva-350898 (URN)10.1002/jbmr.3331 (DOI)000426731100017 ()29220072 (PubMedID)
Funder
Swedish Research Council
Available from: 2018-05-17 Created: 2018-05-17 Last updated: 2018-05-17Bibliographically approved
Westerberg, P.-A., Sterner, G., Ljunggren, Ö., Isaksson, E., Elvarson, F., Dezfoolian, H. & Linde, T. (2018). High doses of cholecalciferol alleviate the progression of hyperparathyroidism in patients with CKD Stages 3-4: results of a 12-week double-blind, randomized, controlled study. Nephrology, Dialysis and Transplantation, 33(3), 466-471
Open this publication in new window or tab >>High doses of cholecalciferol alleviate the progression of hyperparathyroidism in patients with CKD Stages 3-4: results of a 12-week double-blind, randomized, controlled study
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2018 (English)In: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385, Vol. 33, no 3, p. 466-471Article in journal (Refereed) Published
Abstract [en]

Background: Calcidiol insufficiency may accelerate the development of secondary hyperparathyroidism (SHPT). We tested the effect of a substantial increase in calcidiol on mineral metabolism in patients with chronic kidney disease (CKD).

Methods: Ninety-five patients with CKD Stages 3-4, parathyroid hormone (PTH) above 6.8 pmol/L and calcidiol below 75 nmol/L were randomized to receive either cholecalciferol 8000 IU/day or placebo for 12 weeks. The primary endpoint was difference in the mean change in iPTH after 12 weeks. The proportion of participants having a 30% reduction in PTH and the effect on hand grip strength, fatigue and different biochemical variables were also investigated.

Results: Baseline calcidiol was 57.5 ± 22 and 56.8 ± 22 nmol/L in the cholecalciferol and placebo groups, respectively. The corresponding concentrations of PTH were 10.9 ± 5 and 13.1 ± 9 pmol/L. Calcidiol increased to 162 ± 49 nmol/L in patients receiving cholecalciferol, and PTH levels remained constant at 10.5 ± 5 pmol/L. In the placebo group, calcidiol remained stable and PTH increased to 15.2 ± 11 pmol/L. The mean change in PTH differed significantly between the two groups (P < 0.01). The proportion of subjects reaching a 30% decrease in PTH did not differ. No effect on grip strength, fatigue, phosphate or fibroblast growth factor 23 was observed. Cholecalciferol treatment resulted in stable calcium concentrations and a substantial increase in calcitriol.

Conclusion: Treatment with high daily doses of cholecalciferol in patients with CKD Stages 3-4 halts the progression of SHPT and does not cause hypercalcaemia or other side effects.

Keywords
FGF23, cholecalciferol, chronic renal failure, secondary hyperparathyroidism, vitamin D
National Category
Urology and Nephrology
Identifiers
urn:nbn:se:uu:diva-342579 (URN)10.1093/ndt/gfx059 (DOI)000426868500017 ()29156056 (PubMedID)
Available from: 2018-02-22 Created: 2018-02-22 Last updated: 2018-05-23Bibliographically approved
Kristjansdottir, H., Lewerin, C., Lerner, U., Waern, E., Ljunggren, Ö., Johansson, H., . . . Mellstrom, D. (2017). Both High And Low Serum Serotonin Levels Predict Incident Non-Vertebral Fractures. Paper presented at WCO-IOF-ESCEO World Congress on Osteoporosis, Osteoarthritis and Musculoskeletal Diseases, MAR 23-26, 2017, Florence, ITALY. Osteoporosis International, 28, S181-S182
Open this publication in new window or tab >>Both High And Low Serum Serotonin Levels Predict Incident Non-Vertebral Fractures
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2017 (English)In: Osteoporosis International, ISSN 0937-941X, E-ISSN 1433-2965, Vol. 28, p. S181-S182Article in journal, Meeting abstract (Other academic) Published
National Category
Endocrinology and Diabetes
Identifiers
urn:nbn:se:uu:diva-347302 (URN)000406278600265 ()
Conference
WCO-IOF-ESCEO World Congress on Osteoporosis, Osteoarthritis and Musculoskeletal Diseases, MAR 23-26, 2017, Florence, ITALY
Available from: 2018-04-03 Created: 2018-04-03 Last updated: 2018-04-03Bibliographically approved
Jonsson, E., Hansson-Hedblom, A., Ljunggren, Ö., Akesson, K., Spangeus, A., Borgstrom, F. & Kanis, J. A. (2017). Cost-Effectiveness Of Complying With Treatment Guidelines In Sweden. Paper presented at WCO-IOF-ESCEO World Congress on Osteoporosis, Osteoarthritis and Musculoskeletal Diseases, MAR 23-26, 2017, Florence, ITALY. Osteoporosis International, 28, S440-S440
Open this publication in new window or tab >>Cost-Effectiveness Of Complying With Treatment Guidelines In Sweden
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2017 (English)In: Osteoporosis International, ISSN 0937-941X, E-ISSN 1433-2965, Vol. 28, p. S440-S440Article in journal, Meeting abstract (Other academic) Published
National Category
Health Care Service and Management, Health Policy and Services and Health Economy
Identifiers
urn:nbn:se:uu:diva-347301 (URN)000406278601034 ()
Conference
WCO-IOF-ESCEO World Congress on Osteoporosis, Osteoarthritis and Musculoskeletal Diseases, MAR 23-26, 2017, Florence, ITALY
Available from: 2018-04-03 Created: 2018-04-03 Last updated: 2018-04-03Bibliographically approved
Mellstrom, D., Ohlsson, C., Ljunggren, Ö., Lorentzon, M., Nilsson, A. G., Lewerin, C., . . . Karlsson, M. (2017). Increased Risk For Incident Hip Fracture In Men With Type 2 Diabetes. Paper presented at WCO-IOF-ESCEO World Congress on Osteoporosis, Osteoarthritis and Musculoskeletal Diseases, MAR 23-26, 2017, Florence, ITALY. Osteoporosis International, 28, S529-S530
Open this publication in new window or tab >>Increased Risk For Incident Hip Fracture In Men With Type 2 Diabetes
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2017 (English)In: Osteoporosis International, ISSN 0937-941X, E-ISSN 1433-2965, Vol. 28, p. S529-S530Article in journal, Meeting abstract (Other academic) Published
National Category
Endocrinology and Diabetes
Identifiers
urn:nbn:se:uu:diva-347303 (URN)000406278601222 ()
Conference
WCO-IOF-ESCEO World Congress on Osteoporosis, Osteoarthritis and Musculoskeletal Diseases, MAR 23-26, 2017, Florence, ITALY
Available from: 2018-04-03 Created: 2018-04-03 Last updated: 2018-04-03Bibliographically approved
Zillikens, M. C., Demissie, S., Hsu, Y.-H., Yerges-Armstrong, L. M., Chou, W.-C., Stolk, L., . . . Kiel, D. P. (2017). Large meta-analysis of genome-wide association studies identifies five loci for lean body mass. Nature Communications, 8, Article ID 80.
Open this publication in new window or tab >>Large meta-analysis of genome-wide association studies identifies five loci for lean body mass
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2017 (English)In: Nature Communications, ISSN 2041-1723, E-ISSN 2041-1723, Vol. 8, article id 80Article in journal (Refereed) Published
Abstract [en]

Lean body mass, consisting mostly of skeletal muscle, is important for healthy aging. We performed a genome-wide association study for whole body (20 cohorts of European ancestry with n = 38,292) and appendicular (arms and legs) lean body mass (n = 28,330) measured using dual energy X-ray absorptiometry or bioelectrical impedance analysis, adjusted for sex, age, height, and fat mass. Twenty-one single-nucleotide polymorphisms were significantly associated with lean body mass either genome wide (p < 5 x 10(-8)) or suggestively genome wide (p < 2.3 x 10(-6)). Replication in 63,475 (47,227 of European ancestry) individuals from 33 cohorts for whole body lean body mass and in 45,090 (42,360 of European ancestry) subjects from 25 cohorts for appendicular lean body mass was successful for five single-nucleotide polymorphisms in/ near HSD17B11, VCAN, ADAMTSL3, IRS1, and FTO for total lean body mass and for three single-nucleotide polymorphisms in/ near VCAN, ADAMTSL3, and IRS1 for appendicular lean body mass. Our findings provide new insight into the genetics of lean body mass.

Place, publisher, year, edition, pages
NATURE PUBLISHING GROUP, 2017
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-332854 (URN)10.1038/s41467-017-00031-7 (DOI)000405818900003 ()28724990 (PubMedID)
Funder
Swedish Research CouncilSwedish Foundation for Strategic Research Torsten Söderbergs stiftelseRagnar Söderbergs stiftelse
Available from: 2017-11-08 Created: 2017-11-08 Last updated: 2018-08-24Bibliographically approved
Ohlsson, C., Nethander, M., Kindmark, A., Ljunggren, Ö., Lorentzon, M., Rosengren, B. E., . . . Vandenput, L. (2017). Low Serum DHEAS Predicts Increased Fracture Risk in Older Men: The MrOS Sweden Study. Journal of Bone and Mineral Research, 32(8), 1607-1614
Open this publication in new window or tab >>Low Serum DHEAS Predicts Increased Fracture Risk in Older Men: The MrOS Sweden Study
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2017 (English)In: Journal of Bone and Mineral Research, ISSN 0884-0431, E-ISSN 1523-4681, Vol. 32, no 8, p. 1607-1614Article in journal (Refereed) Published
Abstract [en]

The adrenal-derived hormones dehydroepiandrosterone (DHEA) and its sulfate (DHEAS) are the most abundant circulating hormones and their levels decline substantially with age. DHEAS is considered an inactive precursor, which is converted into androgens and estrogens via local metabolism in peripheral target tissues. The predictive value of serum DHEAS for fracture risk is unknown. The aim of this study was, therefore, to assess the associations between baseline DHEAS levels and incident fractures in a large cohort of older men. Serum DHEAS levels were analyzed with mass spectrometry in the population-based Osteoporotic Fractures in Men study in Sweden (n = 2568, aged 69 to 81 years). Incident X-ray validated fractures (all, n = 594; non-vertebral major osteoporotic, n = 255; hip, n = 175; clinical vertebral, n = 206) were ascertained during a median follow-up of 10.6 years. DHEAS levels were inversely associated with the risk of any fracture (hazard ratio [HR] per SD decrease = 1.14, 95% confidence interval [CI] 1.05-1.24), non-vertebral major osteoporotic fractures (HR = 1.31, 95% CI 1.16-1.48), and hip fractures (HR = 1.18, 95% CI 1.02-1.37) but not clinical vertebral fractures (HR = 1.09, 95% CI 0.95-1.26) in Cox regression models adjusted for age, body mass index (BMI) and prevalent fractures. Further adjustment for traditional risk factors for fracture, bone mineral density (BMD), and/or physical performance variables as well as serum sex steroid levels only slightly attenuated the associations between serum DHEAS and fracture risk. Similarly, the point estimates were only marginally reduced after adjustment for FRAX estimates with BMD. The inverse association between serum DHEAS and all fractures or major osteoporotic fractures was nonlinear, with a substantial increase in fracture risk (all fractures 22%, major osteoporotic fractures 33%) for those participants with serum DHEAS levels below the median (0.60 mg/mL). In conclusion, low serum DHEAS levels are a risk marker of mainly non-vertebral fractures in older men, of whom those with DHEAS levels below 0.60 mg/mL are at highest risk.

Keywords
SEX STEROIDS, GENERAL POPULATION STUDIES, FRACTURE RISK ASSESSMENT, DHEAS, MEN
National Category
Endocrinology and Diabetes Orthopaedics
Identifiers
urn:nbn:se:uu:diva-361235 (URN)10.1002/jbmr.3123 (DOI)000407438800003 ()28276592 (PubMedID)
Funder
Swedish Research CouncilSwedish Foundation for Strategic Research Knut and Alice Wallenberg FoundationThe Lars Erik Lundberg Foundation for Research and EducationNovo NordiskRagnar Söderbergs stiftelseTorsten Söderbergs stiftelse
Available from: 2018-09-26 Created: 2018-09-26 Last updated: 2018-09-26Bibliographically approved
Lewerin, C., Ljunggren, Ö., Nilsson-Ehle, H., Karlsson, M. K., Herlitz, H., Lorentzon, M., . . . Mellström, D. (2017). Low serum iron is associated with high serum intact FGF23 in elderly men: The Swedish MrOS study. Bone, 98, 1-8
Open this publication in new window or tab >>Low serum iron is associated with high serum intact FGF23 in elderly men: The Swedish MrOS study
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2017 (English)In: Bone, ISSN 8756-3282, E-ISSN 1873-2763, Vol. 98, p. 1-8Article in journal (Refereed) Published
Abstract [en]

Background: Fibroblast growth factor (FGF23) is a protein that is produced by osteoblasts and osteocytes. Increased serum levels of FGF23 have been associated with increased risks of osteoporotic fractures and cardiovascular disease, particularly in participants with poor renal function. Serum iron (Fe) has been suggested as a regulator of FGF23 homeostasis. Objective: To determine whether Fe and iron status are determinants of the levels of intact FGF23 (iFGF23) in elderly men. Methods: The MrOS study is a population-based study of elderly men (N = 1010; mean age, 75.3 years; range, 69-81 years). The levels of Fe, transferrin saturation (TS), and ferritin were evaluated in relation to the serum concentrations of iFGF23 before and after adjustments for confounders. Results: TS<15% was found in 3.5% (34/977) of the participants, who had a higher median level iFGF23 compared with the remaining subjects (47.4 mu rnol/L vs. 41.9 mu mol/L, p = 0.008). The levels of iFGF23 correlated negatively (un-adjusted) with the levels of Fe (r = -0.17, p < 0.001), TS (r = -0.16, p < 0.001) and serum ferritin (r = -0.07, p = 0.022). In addition, in participants with estimated glomerular filtration rate eGFRCystatin C > 60 mL/min, the levels of iFGF23 correlated (age-adjusted) negatively with the levels of Fe (r = -0.15, p < 0.001) and TS (r = -0.17, p < 0.001). The level of iFGF23 correlated positively (un-adjusted) with lumbar spine bone mineral density (BMD) (r = 0.14, p < 0.001), total body BMD (r = 0.11, p = 0.001), and total hip BMD (r = 0.09, p = 0.004). The corresponding correlations, when adjusted for age, weight, and height were: r = 0.08, p = 0.018; r = 0.05, p = 0.120; and r = 0.02, p = 0.624, respectively. No associations were found between BMD and the levels of Fe or TS. Multiple step-wise linear regression analyses [adjusting for age, body mass index (BMI), comorbidity index, cystatin C, C-reactive protein (hs-CRP), serum vitamin D 25-OH (25OHD), phosphate, calcium, parathyroid hormone (PTH), erythropoietin, hemoglobin, lumbar spine BMD, apolipoprotein B/A1 ratio] were performed in three separate models with Fe, TS or ferritin as potential explanatory variables. Fe and TS, but not ferritin, were independent predictors of iFGF23 level (standardized beta-values: -0.10, p <0.001; 0.10, p <0.001; and -0.05, p = 0.062, respectively). Conclusion: Low levels of Fe in elderly men are associated with high levels of iFGF23, independently of markers of inflammation and renal function, suggesting an iron-related pathway for FGF23 regulation. (C) 2017 Elsevier Inc. All rights reserved.

Place, publisher, year, edition, pages
Elsevier, 2017
Keywords
Elderly, Men, Iron, Fibroblast growth factor 23, Intact FGF23, Bone mineral density
National Category
Endocrinology and Diabetes
Identifiers
urn:nbn:se:uu:diva-322679 (URN)10.1016/j.bone.2017.02.005 (DOI)000400227800001 ()28212898 (PubMedID)
Available from: 2017-05-29 Created: 2017-05-29 Last updated: 2017-05-29Bibliographically approved
Vandenput, L., Mellstrom, D., Laughlin, G. A., Cawthon, P. M., Cauley, J. A., Hoffman, A. R., . . . Ohlsson, C. (2017). Low Testosterone, but Not Estradiol, Is Associated With Incident Falls in Older Men: The International MrOS Study. Journal of Bone and Mineral Research, 32(6), 1174-1181
Open this publication in new window or tab >>Low Testosterone, but Not Estradiol, Is Associated With Incident Falls in Older Men: The International MrOS Study
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2017 (English)In: Journal of Bone and Mineral Research, ISSN 0884-0431, E-ISSN 1523-4681, Vol. 32, no 6, p. 1174-1181Article in journal (Refereed) Published
Abstract [en]

Fracture risk is determined by bone strength and the risk of falls. The relationship between serum sex steroids and bone strength parameters in men is well known, whereas the predictive value of sex steroids for falls is less studied. The aim of this study was to assess the associations between serum testosterone (T) and estradiol (E2) and the likelihood of falls. Older men (aged > 65 years) from the United States (n = 1919), Sweden (n = 2495), and Hong Kong (n = 1469) participating in the Osteoporotic Fractures in Men Study had baseline T and E2 analyzed by mass spectrometry. Bioavailable (Bio) levels were calculated using mass action equations. Incident falls were ascertained every 4 months during a mean follow-up of 5.7 years. Associations between sex steroids and falls were estimated by generalized estimating equations. Fall rate was highest in the US and lowest in Hong Kong (US 0.50, Sweden 0.31, Hong Kong 0.12 fall reports/person/year). In the combined cohort of 5883 men, total T (odds ratio [OR] per SD increase = 0.88, 95% confidence interval [CI] 0.86-0.91) and BioT (OR = 0.86, 95% CI 0.83-0.88) were associated with incident falls in models adjusted for age and prevalent falls. These associations were only slightly attenuated after simultaneous adjustment for physical performance variables (total T: OR = 0.94, 95% CI 0.91-0.96; BioT: OR = 0.91, 95% CI 0.89-0.94). E2, BioE2, and sex hormone-binding globulin (SHBG) were not significantly associated with falls. Analyses in the individual cohorts showed that both total T and BioT were associated with falls in MrOS US and Sweden. No association was found in MrOS Hong Kong, and this may be attributable to environmental factors rather than ethnic differences because total T and BioT predicted falls in MrOS US Asians. In conclusion, low total T and BioT levels, but not E2 or SHBG, are associated with increased falls in older men.

Keywords
SEX STEROIDS, FALLS, PHYSICAL PERFORMANCE, GENERAL POPULATION STUDIES, MEN
National Category
Endocrinology and Diabetes
Identifiers
urn:nbn:se:uu:diva-329695 (URN)10.1002/jbmr.3088 (DOI)000403220400005 ()28135013 (PubMedID)
Funder
Swedish Research CouncilSwedish Foundation for Strategic Research Torsten Söderbergs stiftelseRagnar Söderbergs stiftelseNovo Nordisk
Available from: 2017-10-10 Created: 2017-10-10 Last updated: 2017-10-10Bibliographically approved
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