The research, led by Dr. Wen-Hsuan Tsai and colleagues from the Division of Endocrinology and Metabolism, Department of Internal Medicine, MacKay Memorial Hospital, Taipei, Taiwan, highlights how diabetes can worsen bone health outcomes in EC patients, even though EC alone does not independently elevate fracture risk.
The study analyzed data from the Taiwan National Cancer Registry and the National Health Insurance Research Database, encompassing over 20,000 patients with endometrial cancer diagnosed between 2007 and 2018. Researchers aimed to determine whether EC or coexisting diabetes increased fracture risk, accounting for other factors such as comorbidities, cancer therapy, hormone receptor status, and disease stage.
The study led to the following notable findings:
- Among 15,505 endometrial cancer patients, 3,044 had diabetes mellitus (DM), while 12,461 did not.
- EC alone was not linked to an increased risk of fractures compared with the general population.
- The coexistence of diabetes with EC significantly raised the risk of fractures across multiple categories.
- EC patients with diabetes had a 137% higher risk of hip fractures (HR 2.37) compared to those without diabetes.
- They also showed a 71% higher risk of vertebral fractures (HR 1.71).
- The risk of osteoporotic fractures increased by 29% in EC patients with diabetes (HR 1.29).
- Diabetes did not have a significant impact on the likelihood of upper extremity fractures (HR 1.33).
The findings suggest that diabetes contributes substantially to bone fragility among EC patients, likely due to metabolic disturbances, microvascular complications, and changes in bone quality associated with chronic hyperglycemia. The authors emphasized that the dual burden of cancer and diabetes may accelerate bone loss and increase susceptibility to fractures, underlining the importance of close monitoring and proactive bone health management in this patient population.
While the study’s large, nationwide cohort strengthens its reliability, the researchers acknowledged several limitations. Because the study was observational and not randomized, it cannot confirm causality between diabetes and fracture risk. Additionally, the timing and location of fractures could not be precisely determined, and variations in hormone therapy—some of which strengthen bones while others weaken them—may have influenced the results. Moreover, certain cancer-related factors, such as estrogen levels, receptor status, and treatment modalities, may have interacted in complex ways that were not fully captured.
The authors recommended that future studies explore these interactions using more advanced analytical approaches, such as stratification by hormone receptor status or cancer stage, to better understand how these factors contribute to fracture risk.
The study found that while endometrial cancer alone does not increase fracture risk, the presence of diabetes significantly heightens the likelihood of hip, vertebral, and osteoporotic fractures. Given these findings, clinicians should pay particular attention to bone health in women with EC and diabetes.
The researchers stressed that additional comprehensive and prospective studies are needed to validate these results and guide tailored preventive strategies.
Reference:
Tsai, W., Hsu, M., Weng, C., Hsu, H., Hsieh, C., Yeh, T., Chien, K., Lee, C., Chien, M., & Tsai, M. (2025). Association between endometrial cancer and subsequent risk of fracture: A national cohort study. Frontiers in Endocrinology, 16, 1570426. https://doi.org/10.3389/fendo.2025.1570426
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