Comparable Effects of Zoledronate on Fracture Incidence in Postmenopausal Osteoporotic Women With and Without Diabetes: A 5-Year Prospective Study

Purpose: Zoledronate is most effective when bone turnover is elevated, as in postmenopausal women. In type 2 diabetes mellitus (T2DM), lower bone turnover leads to smaller bone mineral density (BMD) gains compared to non-diabetic (NDM) individuals, and fractures often occur despite preserved BMD. It is unclear whether zoledronate reduces fracture risk in T2DM. No prospective study has directly compared its fracture-preventing efficacy between women with and without T2DM. Aims : To estimate the effect of zoledronate on fracture incidence over 60 months in postmenopausal osteoporotic women with and without T2DM. Methods: This prospective cohort included postmenopausal women with BMD T-scores ≤ –2.5 at either the lumbar spine, femoral neck, or hip. Participants were classified as T2DM or NDM. All received annual zoledronate (4 mg), daily calcium (1000 mg), and cholecalciferol (500 IU), with standardized fall-prevention measures. Fracture history was recorded at follow-up visits, and annual spine radiographs were performed to detect morphometric vertebral fractures. Women completing ≥60 months were included in final analysis. The primary endpoint was fracture incidence; secondary endpoints were changes in BMD and bone turnover markers (BTMs). Results: Of 183 women enrolled, 150 completed 5 years (63 T2DM, 87 NDM; median age 59 years). Baseline BMD was similar, but BTMs were lower in T2DM. During a median 63.5 months, 20 new fractures occurred in 15 women: 8 (12.7%) with T2DM and 7 (8.0%) without. The relative risk was 1.58 (95% confidence interval, 0.60–4.13; P = 0.2). Both groups showed comparable BMD improvements. Conclusion: Annual zoledronate prevented fractures equally in postmenopausal osteoporotic women with and without T2DM over 5 years, indicating similar efficacy despite differences in baseline bone turnover.