Association of Diabetic Retinopathy Severity with Bone Mineral Density and Fragility Fracture Risk in Adults with Type 2 Diabetes Mellitus: A Prospective Cohort Study

Abstract

Background: Type 2 diabetes mellitus is associated with increased skeletal fragility despite relatively preserved bone mineral density (BMD). Diabetic retinopathy may indicate systemic complications associated with skeletal vulnerability. Retinal microvascular injury and altered skeletal metabolism may share mechanisms involving hyperglycemia, inflammation, and vascular dysfunction.

Objective: To examine associations between retinopathy severity, site-specific BMD, and incident fragility fractures in adults with type 2 diabetes.

Methods: This multicenter prospective cohort included 170 adults recruited in three tertiary care hospitals of Pakistan between March 2025 and April 2026. Retinopathy was classified as absent, mild-to-moderate nonproliferative, or severe nonproliferative/proliferative disease. BMD was measured using dual-energy X-ray absorptiometry. Multivariable linear regression assessed BMD associations; fractures were assessed during follow-up using incidence rates and exploratory Cox regression.

Results: Participants included 80 men and 90 women; 55 had no retinopathy, 74 had mild-to-moderate disease, and 41 had advanced disease. Mean femoral neck BMD declined across groups (0.843 ± 0.076, 0.785 ± 0.072, and 0.746 ± 0.076 g/cm², respectively; p < 0.001). After adjustment, advanced retinopathy was associated with lower femoral neck BMD (β = −0.102 g/cm²; 95% confidence interval, −0.140 to −0.064). Twelve fragility fractures occurred over 164.08 person-years. Fracture incidence was highest in advanced retinopathy (156.9 per 1,000 person-years), but the unadjusted hazard ratio was imprecise (4.30; 95% confidence interval, 0.87–21.30; p = 0.074).

Conclusion: Greater retinopathy severity was associated with lower BMD, whereas evidence for increased incident fracture risk remained inconclusive. Larger cohorts with extended follow-up are needed.