Antiresorptive therapy and newly diagnosed diabetes in women: a historical cohort study

Aims: Undercarboxylated osteocalcin (ucOC) promotes increased insulin sensitivity and increased secretion. Since antiresorptive therapy (AT) decreases ucOC levels, AT could increase the risk of diabetes and this would have serious clinical ramifications. We sought to test this hypothesis by examining the association between new use of AT and newly-diagnosed diabetes. Methods: Using a bone mineral density (BMD) registry for Manitoba, Canada, we identified 33 640 women aged >= 50 years without diabetes at their first BMD test for 1998-2013. We linked these women to a province-wide retail pharmacy database to identify new AT exposure each year for up to 5 years after a BMD test. Time-dependent analysis was used to test the independent association between new use of AT and newly diagnosed diabetes. Results: This cohort had a mean age of 65 years, a mean body mass index of 26.8 kg/m(2), and 12% were receiving glucocorticoid and 13% hormone replacement therapy at BMD test. In the first year after BMD test, 29% of women started AT (bisphosphonates, 92%). Over a mean 4.2 years of follow-up, 3.7% new AT users and 4.2% non-users had diabetes (adjusted hazard ratio 1.01, 95% confidence interval 0.87-1.16). Sensitivity analyses using AT dose-response gradients also found no significant associations with diabetes. Conclusions: Despite the plausible biological mechanisms related to ucOC, new use of AT was not a risk factor for diabetes in this cohort. The clinical implications of these findings are reassuring, as AT is widely prescribed for treating osteoporosis in older women who are also at high risk of developing diabetes.