Insulin use and Excess Fracture Risk in Patients with Type 2 Diabetes: A Propensity-Matched cohort analysis

Eladio Losada-Grande,Samuel Hawley,Manel Puig-Domingo,Xavier Nogues,Daniel Martinez-Laguna,Dídac Mauricio,Berta Soldevila,Daniel Prieto-Alhambra,Adolfo Diez-Perez

doi:10.1038/s41598-017-03748-z

Abstract

Despite normal to high bone mineral density, patients with type 2 diabetes (T2DM) have an increased fracture risk. T2DM medications could partially account for this excess risk. The aim of this study was to assess the association between insulin use and bone fracture risk in T2DM patients. A population-based matched cohort study based on a primary care records database validated for research use (Catalonia, Spain) was performed. Propensity score (PS) for insulin use was calculated using logistic regression including predefined predictors of fractures. A total of 2,979 insulin users and 14,895 non-users were observed for a median of 1.42 and 4.58 years respectively. Major fracture rates were 11.2/1,000 person-years for insulin users, compared with 8.3/1,000 among non-users. Matched models confirmed a significant association, with an adjusted subhazard ratio (adj SHR) of 1.38 [95% CI 1.06 to 1.80] for major fractures. No differences between types of insulin or different regimens were found. Estimated number needed to harm (fracture) was 82 (95% CI 32 to 416). Insulin use appears to be associated with a 38% excess fracture risk among T2DM patients in the early stages of the disease. Fracture risk should be included among the considerations to initiate insulin treatment.

Highlights

Despite normal to high bone mineral density, patients with type 2 diabetes (T2DM) have an increased fracture risk
Baseline characteristics differed significantly between insulin users and non-users in terms of: age, body mass index (BMI), socio-economic status (SES), smoking status, alcohol intake, previous falls, glomerular filtration rate (GFR), neuropathy, HbA1c level, use of medications related with fracture risk, use of some antidiabetic medications, and index year of diagnosis
At least one major fracture occurred in 60/2979 insulin users and 631/14,895 Propensity score (PS)-matched non-users, an equivalent to incidence rates of 11.2/1,000 and 8.3/1,000 PY, respectively

Summary

Introduction

Despite normal to high bone mineral density, patients with type 2 diabetes (T2DM) have an increased fracture risk. The aim of this study was to assess the association between insulin use and bone fracture risk in T2DM patients. Insulin use appears to be associated with a 38% excess fracture risk among T2DM patients in the early stages of the disease. Risk factors associated with fracture risk in T2DM include duration of disease[7, 9, 14], diabetic complications [impaired vision[1, 14], peripheral neuropathy[20], orthostatic hypotension[21], etc.], episodes of hypoglycaemia[22], increased risk of falling[20, 22,23,24], inadequate glycaemic control[25], and some antidiabetic medications that appear to affect bone metabolism, such as glitazones[26, 27]. No direct negative effect of insulin therapy on bone has yet been directly demonstrated in randomised controlled trials

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