Bisphosphonates May Benefit Postmenopausal Women With Diabetes

Woman testing blood sugar
Woman testing blood sugar
Fracture risk may be lower with bisphosphonates in women with diabetes.

SEATTLE — Bisphosphonates appear to be an effective treatment option for older women with diabetes, according to a new pooled, post-hoc analysis of data from the FIT and HORIZON trials.

The results, which were presented at the American Society for Bone and Mineral Research (ASBMR) 2015 Annual Meeting, suggest that alendronate and zoledronic acid help preserve bone density and reduce fracture risk in postmenopausal women with type 2 diabetes.

There has been speculation that the antiresorptive mechanism in bisphosphonates may not be as effective for fracture prevention in patients with type 2 diabetes as it is in patients without diabetes. Although studies have shown that the effects of alendronate on bone mineral density (BMD) are similar in women, regardless of whether or not they have diabetes, there have been no formal assessments that have looked specifically at the anti-fracture efficacy of bisphosphonates in patients with type 2 diabetes in a randomized, clinical trial.

“This is the first study to look at this issue using randomized trial data for the bisphosphonates,” said lead study author Ann Schwartz, PhD, professor in the department of epidemiology and biostatistics at the University of California, San Francisco.

She noted that older adults with type 2 diabetes have higher fracture risk at a given BMD, indicating that bone in patients with diabetes is more fragile at a given BMD. Nevertheless, the reasons for this increased fragility are unclear. 

“One hypothesis is that bone properties are compromised by greater accumulation of advanced glycation end products (AGEs) in bone collagen. Reduced bone turnover — a characteristic of diabetes — as well as hyperglycemia may contribute to higher AGE levels. In this context of lower turnover and higher AGEs, there are theoretical concerns that bisphosphonates may not be effective in preventing fractures in diabetic patients because their antiresorptive action will further suppress bone turnover,” Dr Schwartz told Endocrinology Advisor.

FIT (Fracture Intervention Trial) included 6459 postmenopausal women with femoral neck T-score ≤ –1.6. All patients were given alendronate 5 mg to 10 mg or placebo daily for up to 4 years.

HORIZON (Health Outcomes and Reduced Incidence with Zoledronic Acid Once Yearly-Pivotal Fracture Trial) included 7736 postmenopausal women with osteoporosis based on femoral neck T-score and/or baseline vertebral fracture. All patients received a once yearly infusion of zoledronic acid 5 mg or placebo for up to 3 years.

Dr Schwartz and colleagues identified baseline diabetes from self-report, diabetes medication use, or elevated fasting glucose (≥126 mg/dL) or nonfasting glucose (>200 mg/dL).

For this investigation, incident nonvertebral fractures were centrally adjudicated, and morphometric vertebral fractures from spine X-rays at annual visits were also included. 

The researchers used Cox models to estimate treatment efficacy in women with and without diabetes for clinical fractures, with stratification of the baseline hazard by trial and diabetes status. They employed logistic regression for morphometric vertebral fractures with diabetes status and trial as covariates.

At baseline, mean age was 68 years in FIT and 73 years in HORIZON. Mean BMIs was 25.1 and 25.3, respectively.

Results showed that 87 of 869 women with diabetes and 1411 of 13 288 women without diabetes experienced at least one nonvertebral fracture. The analysis also identified 44 of 769 women with diabetes with at least one morphometric vertebral fracture and 786 of 12 312 women without diabetes with at least one morphometric vertebral fracture.

According to the data, treatment with a bisphosphonate reduced the risk for nonvertebral and morphometric vertebral fractures in women with and without diabetes, as compared with placebo.

When evaluating just patients with diabetes, the relative risk for nonvertebral fracture was 0.52, and the relative risk for morphometric vertebral fracture was 0.34 with bisphosphonates, as compared with placebo.

In light of these results, the researchers concluded that the anti-fracture efficacy of these two bisphosphonates is not inferior in older women with type 2 diabetes compared with older women without diabetes. 

“The take-home message is that bisphosphonates are an effective treatment for the reduction of vertebral and nonvertebral fracture incidence in diabetic women,” Dr Schwartz told Endocrinology Advisor. “However, the results are limited to postmenopausal women with low BMD and/or prevalent vertebral fracture.”


  1. Schwartz A. Abstract 1141: Bisphosphonates reduce fracture risk in postmenopausal women with diabetes: Results from FIT and HORIZON trials. Presented at: American Society for Bone and Mineral Research (ASBMR) 2015 Annual Meeting; Oct. 9-12, 2015; Seattle.