• Kristian F Axelsson, Henrik Litsne, Konstantina Kousoula, Stefan Franzén, Björn Eliasson, and Mattias Lorentzon.
• Sahlgrenska Osteoporosis Centre, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
• PLoS Med. 2023 Jan 1; 20 (1): e1004172e1004172.

BackgroundType 2 diabetes mellitus (T2DM) is considered a risk factor for fracture but the evidence regarding the impact of T2DM on fracture risk is conflicting. The objective of the study was to determine if patients with T2DM have increased fracture risk and if T2DM-related risk factors could be identified.Methods And FindingsIn this national cohort study in Sweden, we investigated the risk of fracture in 580,127 T2DM patients, identified through the national diabetes register including from both primary care and hospitals, and an equal number of population-based controls without diabetes matched for age, sex, and county from 2007 to 2017. The mean age at entry was 66.7 years and 43.6% were women. During a median follow-up time of 6.6 (interquartile range (IQR) 3.1 to 9.8) years, patients with T2DM had a marginally but significantly increased risk of major osteoporotic fracture (MOF) (hazard ratio (HR) 1.01 (95% confidence interval [CI] 1.00 to 1.03)) and hip fracture (HR 1.06 (95% CI 1.04 to 1.08)) compared to controls, associations that were only minimally affected (HR 1.05 (95% CI 1.03 to 1.06) and HR 1.11 (95% CI 1.09 to 1.14), respectively) by multivariable adjustment (age, sex, marital status, and an additional 20 variables related to general morbidity, cardiovascular status, risk of falls, and fracture). In a multivariable-adjusted Cox model, the proportion of the risk for all fracture outcomes (Heller's R2) explained by T2DM was below 0.1%. Among the T2DM patients, important risk factors for fracture were a low BMI (<25 kg/m2), long diabetes duration (≥15 years), insulin treatment, and low physical activity. In total, 55% of the T2DM patients had none of these risk factors and a significantly lower fracture risk than their respective controls. The relatively short mean duration of T2DM and lack of bone density data, constitute limitations of the analysis.ConclusionIn this study, we observed only a marginally increased fracture risk in T2DM, a condition that explained less than 0.1% of the fracture risk. Consideration of the herein identified T2DM-related risk factors could be used to stratify T2DM patients according to fracture risk.Copyright: © 2023 Axelsson et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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