Endocrine Abstracts

Objective: Type 2 diabetes mellitus (T2DM) patients have a higher risk for bone fractures, especially in the elderly. However, bone mineral density (BMD) does not reflect their increased bone fragility, potentially based on disturbed bone metabolism or quality. MicroRNAs are promising new biomarkers for fracture risk detection. This study aimed to find specific miRNAs in a large cohort of elderly patients with and without T2DM at risk for osteoporotic fractures.

Methods: This nursing home cohort includes 249 T2DM patients and 301 nonT2DM patients as controls. Fractures were recorded within 2 years after the first visit. Mobility scores of the patients, fracture and medical history were documented and blood samples were taken to measure bone turnover and vitamin D. miRNA sequencing using serum samples was performed by QIAGEN microRNA-seq Service. Surrogate markers were used to correlate candidate miRNAs with bone biomarkers. Target predictions were performed with online target prediction tools (miRanda, TargetScan).

Results: Mean age of the cohort was 84.4±6.3 years, mean BMI 25.4±4.7. Hip fractures occurred in 34% of the T2DM patients within 2 years after the first visit, compared to 15% in the nonT2DM group (P<0.0001). NonT2DM patients without fractures had significantly higher mobility scores (P<0.01) as compared to nonT2DM patients with fractures or the respective T2DM groups. Vitamin D levels were different between nonT2DM with- and without fracture (P<0.01) but not between the T2DM and the nonT2DM patients. Comparison of miRNA sequencing results between T2DM patients with and without fractures showed specific differences in the miRNA sequencing profiles among the two groups.

Summary and Conclusion: In this cohort of very old patients with and without T2DM of comparable age and BMI, we found a very low vitamin D status, though fracture groups showed slightly higher vitamin D. We found a number of microRNA differences between diabetic fracture and non-fracture patients, with most promising candidates. MicroRNAs might serve as important biomarkers in the prediction of bone fracture risk in osteoporotic and especially T2DM patients, where existing diagnostic tools do not allow for concise fracture risk prediction.