Predictors of mortality subsequent to a fracture in diabetes mellitus patients

Background: Type-1 and type-2 Diabetes Mellitus (DM) is associated with an increased fracture risk and possibly an increased risk of death following a fracture.Aim: To investigate the association between diabetes related drugs and mortality following a fracture. Methods: A nested case-control study was conducted. Cases were patients with DM who died following a fracture; controls were DM patients not dying after a fracture. We identified DM patients using the Danish National Hospital Discharge Register (1977-2011) and included information on date of DM diagnosis, date of fracture and comorbidities. From the Danish Cause of Death Register the date of death was collected (2008-2011). From the Central Region of Jutland, Denmark, medication use was collected (2008-2011). Analysis was performed by unconditional logistic regression.Results: 2,621 diabetes patients with a fracture following the diabetes diagnosis and with information on medication use were included. Of these 229 died. In a multivariate analysis, statin use (n= 1,106 (42%) statin users, odds ratio (OR) = 0.60, 95 % confidence interval, p=0.012) decreased the risk of dying subsequent to a fracture. Male gender (OR=1.57, p=0.005), increasing age (OR=1.08, p<0.001), a diagnosis of retinopathy (OR=2.12, p=0.008), heart failure (OR= 1.68, p=0.004) and use of glucocorticoids (OR=2.22, p=0.001) were associated with an increased risk of death. None of the antidiabetics; biguanides, glucagon-like receptor agonists, β-cell stimulants, glitazones, and insulin were associated with mortality.Conclusion: Co-morbidity reflected by late onset complications, heart failure and glucocorticoid use was associated with an increased risk of mortality subsequent to a fracture. Statin use may reduce mortality subsequent to a fracture in diabetes patients. Clinical trials are needed to determine whether diabetes patients with a fracture should initiate statin treatment

Risk of fracture with thiazolidinediones: an individual patient data meta-analysis.

BACKGROUND: The use of thiazolidinediones (TZDs) has been associated with increased fracture risks. Our aim was to estimate the risk of fracture with TZDs in three different healthcare registries, using exactly the same study design, and to perform an individual patient data meta-analysis of these three studies. METHODS: Population-based cohort studies were performed utilizing the British General Practice Research Database (GPRD), the Dutch PHARMO Record Linkage System (RLS), and the Danish National Health Registers. In all three databases, the exposed cohort consisted of all patients (aged 18+) with at least one prescription of antidiabetic (AD) medication. Cox proportional hazards models were used to estimate hazard ratios (HRs) of fracture. The total period of follow-up for each patient was divided into periods of current exposure and past exposure, with patients moving between current and past use. RESULTS: In all three registries, the risk of fracture was increased for women who were exposed to TZDs: HR 1.48 (1.37-1.60) in GPRD, HR 1.35 (1.15-1.58) in PHARMO, and HR 1.22 (1.03-1.44) in Denmark. Combining the data in an individual patient data meta-analysis resulted, for women, in a 1.4-fold increased risk of any fracture for current TZD users versus other AD drug users [adj. HR 1.44 (1.35-1.53)]. For men, there was no increased fracture risk [adj. HR 1.05 (0.96-1.14)]. Risks were increased for fractures of the radius/ulna, humerus, tibia/fibula, ankle, and foot, but not for hip/femur or vertebral fractures. Current TZD users with more than 25 TZD prescriptions ever before had a 1.6-fold increased risk of fracture compared with other AD drug users [HR 1.59 (1.46-1.74)]. CONCLUSION: In this study, we consistently found a 1.2- to 1.5-fold increased risk of fractures for women using TZDs, but not for men, across three different healthcare registries. TZD users had an increased risk for fractures of the extremities, and risks further increased for prolonged users of TZDs