Risk of fracture in adults with type 2 diabetes in Sweden: A national cohort study

Abstract

Background Type 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 findings In 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. Conclusion In 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.

When Cortical Bone Matrix Properties Are Indiscernible between Elderly Men with and without Type 2 Diabetes, Fracture Resistance Follows Suit

“…( 34 ) While this might not affect every T2DM patient, the authors postulate that 21 million individuals are affected by a risk factor profile contributing to increased fracture risk. ( 34 ) A longer diabetes duration signifies prolonged high glucose condition within the body, which affects osseos cellular activity, leading to low bone turnover in T2D, which can result in more highly mineralized bone tissue and absence of microcrack removal. Additionally, the longer the high glucose condition continues, the more AGEs can be formed and, thus, impair collagen properties within the bone tissue.…”

Bone metabolism in diabetes: a clinician’s guide to understanding the bone–glucose interplay

“…Studies examining fractures at non-hip sites are even fewer. Fractures of the ribs, humerus and distal leg/ankle are more common in type 2 diabetes [11,12]. Wrist fractures may not be increased in type 2 diabetes [11,12], despite the findings of a meta-analysis [3], which could have been driven by one case-control study.…”

“…Fractures of the ribs, humerus and distal leg/ankle are more common in type 2 diabetes [11,12]. Wrist fractures may not be increased in type 2 diabetes [11,12], despite the findings of a meta-analysis [3], which could have been driven by one case-control study. The risk of vertebral fractures also appears to be elevated in individuals with type 2 diabetes [11,13], although some studies found no difference when compared with those without diabetes [2,3], particularly in men [14].…”

Microvascular Disease Associates with Larger Osteocyte Lacunae in Cortical Bone in Type 2 Diabetes Mellitus

“…In a recent Swedish registry study, fracture risk was higher in patients who were on insulin treatment, with low physical activity, a body mass index (BMI) below 25 kg m À2 , and long-standing disease duration but lower in most (55%) individuals with T2D than in age-and sex-matched background population. (8) Other factors are also considered to increase fracture risk in T2D, including increased risk of falls, poor glycemic control, and diabetes complications, including MVD. (9) Clinical studies based on high-resolution peripheral quantitative computed tomography (HR-pQCT) scans have shown an increased cortical porosity in T2D, (10) which appears to be most pronounced in T2D patients with MVD.…”