J Clin Endocrinol Metab. 2016 Sep 7:jc20162569

Author
Majumdar SR¹, Leslie WD², Lix LM², Morin SN³, Johansson H⁴, Oden A⁴, McCloskey EV⁴, Kanis JA^4,5

Author informaiton
¹University of Alberta, Edmonton, AB, Canada;
²University of Manitoba, Winnipeg, MB, Canada;
³McGill University, Montreal, QC, Canada;
⁴Centre for Metabolic Bone Diseases, University of Sheffield Medical School, UK.;
⁵Institute for Health and Ageing, Catholic University of Australia, Melbourne.

Abstract

CONTEXT:
Type-2 diabetes is associated with higher risk for major osteoporotic fracture (MOF) and hip fracture than predicted by WHO Fracture Risk Assessment (FRAX) tool.

OBJECTIVE:
To examine impact of diabetes duration on fracture risk.

METHODS:
Using a clinical DXA registry linked with Manitoba administrative databases we identified all women age ≥40-years with ≥10years of prior healthcare coverage undergoing hip DXA measurements (1996-2013). Incident MOF and incident hip fractures were each studied over 7years. Cox proportional hazards models were adjusted for FRAX (FRAX-adjusted) and then FRAX plus comorbidity, falls, osteoporosis therapy or insulin (fully-adjusted). FRAX calibration was assessed comparing observed vs predicted probabilities.

RESULTS:
There were 49,098 women without and 8840 women with diabetes (31.4% >10years duration; 20.1% 5-10years; 23.7% <5years; 24.8% new-onset). In FRAX-adjusted analyses, only duration >10years was associated with higher risk for MOF (HR 1.47, 95%CI 1.30-1.66) and this was similar in fully-adjusted models (HR 1.34, 95%CI 1.17-1.54). In contrast, higher risk for hip fracture was seen for all durations in dose-dependent fashion (e.g., FRAX-adjusted HR 2.10, 95%CI 1.71-2.59 for duration >10years vs HR 1.32, 95%CI 1.03-1.69 for new-onset). FRAX significantly underestimated MOF risk (calibration ratio 1.24, 95%CI 1.08-1.39) and hip fracture risk (1.93, 95%CI 1.50-2.35) in those with diabetes duration >10years.

SUMMARY:
Diabetes is a FRAX-independent risk factor for MOF only in women with long-duration diabetes but diabetes increases hip fracture risk regardless of duration. Those with diabetes >10years are at particularly high risk of fracture, and this elevated risk is currently under-estimated by FRAX.