Fracture risk in patients with type 2 diabetes mellitus and possible risk factors: a systematic review and meta-analysis

Abstract

Aim: Patients with type 2 diabetes mellitus (T2DM) have an increased risk of bone fractures. A variable increase in fracture risk has been reported depending on skeletal site, diabetes duration, study design, insulin use, and so on. The present meta-analysis aimed to investigate the association between T2DM with fracture risk and possible risk factors.

Methods: Different databases including PubMed, Institute for Scientific Information, and Scopus were searched up to May 2016. All epidemiologic studies on the association between T2DM and fracture risk were included. The relevant data obtained from these papers were analyzed by a random effects model and publication bias was assessed by funnel plot. All analyses were done by R software (version 3.2.1) and STATA (version 11.1).

Results: Thirty eligible studies were selected for the meta-analysis. We found a statistically significant positive association between T2DM and hip, vertebral, or foot fractures and no association between T2DM and wrist, proximal humerus, or ankle fractures. Overall, T2DM was associated with an increased risk of any fracture (summary relative risk =1.05, 95% confidence interval: 1.04, 1.06) and increased with age, duration of diabetes, and insulin therapy.

Conclusion: Our findings strongly support an association between T2DM and increased risk of overall fracture. These findings emphasize the need for fracture prevention strategies in patients with diabetes.

Keywords: bone; diabetes mellitus; fractures; meta-analysis; osteoporosis; risk factors.

Figure 1

Flowchart of the literature search. Abbreviations: IGT, impaired glucose tolerance; ISI, Institute for Scientific Information; T1DM, type 1 diabetes mellitus.

Figure 2

The results of meta-analysis of the association between type 2 diabetes mellitus and risk of hip fracture. Notes: Each square shows the study specific relative risk estimate. Square sizes are proportional to the weight assigned to the study in the meta-analysis and the horizontal line shows the related 95% CI. The diamond shows the summary relative risk estimate and its width represents the corresponding 95% CI. All statistical tests were two sided. Statistical heterogeneity between studies was assessed with Cochran’s Q test. Meta-analysis was performed by using a random effects method. Abbreviations: CI, confidence interval; ES, effect size.

Figure 3

The results of meta-analysis of the association between type 2 diabetes mellitus and risk of wrist fracture. Notes: Each square shows the study specific relative risk estimate. Square sizes are proportional to the weight assigned to the study in the meta-analysis and the horizontal line shows the related 95% CI. The diamond shows the summary relative risk estimate and its width represents the corresponding 95% CI. All statistical tests were two sided. Statistical heterogeneity between studies was assessed with Cochran’s Q test. Meta-analysis was performed by using a random effects method. Abbreviations: CI, confidence interval; ES, effect size.

Figure 4

The results of meta-analysis of association between type 2 diabetes mellitus and risk of overall fractures. Notes: Each square shows the study specific relative risk estimate. Square sizes are proportional to the weight assigned to the study in the meta-analysis and the horizontal line shows the related 95% CI. The diamond shows the summary relative risk estimate and its width represents the corresponding 95% CI. All statistical tests were two sided. Statistical heterogeneity between studies was assessed with Cochran’s Q test. Meta-analysis was performed by using a random effects method. Abbreviations: CI, confidence interval; ES, effect size.

Figure 5

Begg’s funnel plot for publication bias in the risk difference analysis. Abbreviation: RR, relative risk.

Figure 6

The meta-regression analysis of the relationship between the risk of factors in diabetic patients and the year of study. Abbreviations: CI, confidence interval; Coef, coefficient of variation; REML, restricted (or residual) maximum likelihood estimation; RR, relative risk.