Diabetic neuropathy and fracture risk - a nation-wide case/control study

Fracture risk is increased in type 1 (T1D) and type 2 diabetes (T2D). Diabetic neuropathy may contribute to this risk. We examined the association between diabetes and fracture risk, and whether diabetic neuropathy, including possible painless and possible painful neuropathy, was associated with increased risk of fracture.

In this population-based case-control study, adults (≥18 years) with and without diabetes were identified using Danish health registries. All incident fractures (excluding skull/facial) from 2019 to 2021 were included, and up to three age- and sex-matched controls were selected per case. Diabetes and diabetic neuropathy were defined by ICD and ATC codes; neuropathy was classified as possible painful or painless based on prescriptions for neuropathic pain medications. Associations between diabetes, neuropathy, and fracture risk at different sites were estimated using conditional logistic regression adjusted for confounders.

We included 265,405 individuals with incident fractures and 778,466 matched controls. After multivariable adjustment, fracture risk was increased in T1D (OR 1.68, 95% CI 1.61-1.76) but not in T2D (OR 0.93, 95% CI 0.91-0.94). Diabetic neuropathy was independently associated with higher fracture risk (OR 1.47, 95% CI 1.40-1.55), with the highest risk in possible painful neuropathy (OR 1.62, 95% CI 1.50-1.74). The association between diabetic neuropathy and fracture risk appeared stronger in men and younger individuals. Site-specific analyses suggested larger point estimates for lower leg fractures and comparatively smaller estimates for vertebral, hip and lower arm fractures. The effect of neuropathy did not differ between diabetes type.

Diabetic neuropathy is an independent risk factor for fracture, with particularly high risk in individuals with possible painful neuropathy, potentially due to increased fall risk and impaired bone quality.