Hemoglobin-to-red blood cell distribution width ratio and risk of fragility fracture: A 16-year prospective cohort...

To evaluate the prospective association between the hemoglobin-to-red blood cell distribution width ratio (HRR) and the incidence of fragility fractures in a general Chinese population.

A prospective cohort of 80,515 Chinese adults (mean age: 52.1 years, 79.6 % men) was followed from 2006 to 2023. HRR was calculated as hemoglobin divided by red cell distribution width and categorized into quartiles. The incident fragility fractures were identified via medical records. Cox-proportional hazards models were employed to assess the association between HRR and fracture risk, adjusting for demographics, lifestyle factors, clinical measurements, and medication use. Multiple sensitivity analyses were used to verify the robustness of the results.

Over a mean follow-up of 15.6 years, 1730 participants sustained fragility fractures. Higher HRR was associated with a lower fracture risk. In fully adjusted models, the highest HRR quartile had a 19 % lower risk than the lowest (HR 0.81, 95 % CI 0.70-0.94; P-trend <0.05). Each one SD increase in HRR corresponded to a 7 % reduction in fracture risk (HR 0.93, 95 % CI 0.88-0.97). The inverse association was significant in men and those aged <60 years, but not in women or in individuals aged >60 years. The findings remained robust in sensitivity analyses and competing-risk models.

This large-scale study is the first to demonstrate a significant inverse association between HRR and fragility fracture risk. HRR remained an independent protective factor after multivariable adjustment, and, as a simple, low-cost inflammatory biomarker, it demonstrates potential for early identification and risk stratification of high-risk individuals.