Letter to the Editor Regarding the Article“Is Overweight Protective Against Fracture Occurrence? Age and Site-dependent Different Association Between Body Mass Index and the Incidence of Hip and Vertebral Fractures”

Dear Editor,

I am writing to express my appreciation for the opportunity to review the article titled “Is Overweight Protective Against Fracture Occurrence? Age and Site-Dependent Different Association Between Body Mass Index and the Incidence of Hip and Vertebral Fractures” ¹ by Bae et al., published in the Global Spine Journal. This study reveals the complex relationship between BMI and fracture risk based on large-scale population-based data, providing significant contributions to fracture prevention in humans.

Bae et al. analyzed the association between BMI and fracture risk among 2.5 million adults aged ≥40 years using the Korean National Health Insurance Service database. They identified low BMI as a common risk factor for both hip and vertebral fractures, but demonstrated heterogeneous effects of BMI on these two fracture types. Hip fracture risk showed a linear decrease with increasing BMI, consistent with Wolff’s law regarding mechanical loading protection effects. In contrast, vertebral fracture risk exhibited a U-shaped curve in women and individuals <65 years, potentially linked to obesity-induced sagittal spinal imbalance and restricted compensatory mechanisms. Notably, vertebral fracture risk decreased with higher BMI in elderly males and those ≥65 years.

This study pioneered the differentiation of risk profiles between hip and vertebral fractures, demonstrating that elevated BMI exerts a protective effect against hip fractures while paradoxically increasing vertebral fracture risk, particularly pronounced in women and individuals aged <65 years. These findings unveil the heterogeneous relationship between BMI and fracture risks.

Although this research provides compelling evidence regarding BMI-fracture associations, several aspects merit further investigation:

1. Lack of BMI Trajectory Analysis The study solely relied on baseline BMI measurements, failing to account for the dynamic effects of weight fluctuations on fracture risk during follow-up. Future investigations could incorporate longitudinally collected BMI data to establish time-dependent Cox models. This approach would enable analysis of associations between BMI change patterns (eg, sustained obesity, weight loss, or weight variability) and fracture risk.

2. Incomplete Adjustment for Pharmacological Confounders The study did not include long-term medication data such as antiepileptic and antidepressant drugs that may affect fracture risk. Relevant medication information on long-term use (>3 months) could be extracted from prescription records. Current studies have shown that the fracture risk in epilepsy patients is 2-6 times higher than that in the general population, ² and long-term use of antiepileptic drugs (AEDs) is an independent risk factor for increased fracture risk. ³ Additionally, it has been reported that sustained use of AEDs in female patients aged >65 years can increase the 5-year risk rate of joint fractures by 29%. ⁴

3. Underexplored Socioeconomic Interactions Although the model adjusted for household income, it did not analyze how socioeconomic factors such as education level and occupational type interact with BMI to influence fracture risk. A study reported that higher education level is independently correlated with reduced osteoporosis prevalence. ⁵ Recent analyses indicate that low socioeconomic status is associated with increased hip fracture incidence. ⁶ Additionally, the combined proportion of probable and definite depression among frontline workers reached 22.7%, and both depression and high social stress increase the risk of fragility fractures. ⁷ Future studies could incorporate variables such as education level and occupational type (physical labor/non-physical labor). The interaction terms between BMI and socioeconomic factors should be tested—for example, analyzing whether low education level exacerbates the risk of vertebral fractures associated with high BMI.

In conclusion, I would like to extend my gratitude to the Global Spine Journal and the authors for their contributions to advancing our understanding of fracture risk. This study not only elucidates the relationship between BMI and hip and vertebral fractures, but also reflects the importance of personalized fracture prevention strategies, providing a basis for precision medicine.