Abstract
The recent NHANES-based study by Zhan et al. (2025) investigated the association between the dietary index for gut microbiota (DI-GM) and osteoporosis, reporting that higher DI-GM scores were linked to lower osteoporosis prevalence. While the study provides valuable exploratory evidence, several limitations may affect its clinical and public health implications. First, residual confounding may remain, as weight-bearing exercise, vitamin D status, calcium/phosphate metabolism, sex hormones, and family history were not incorporated. Second, generalizability is constrained: the sample was predominantly White and higher-income, dietary cultures shape gut microbiota composition, and osteopenia-a key prevention target-was excluded. Third, the absence of subgroup analyses may obscure heterogeneity across high-risk groups, especially postmenopausal women, in whom pathophysiological drivers and intervention effects differ. Finally, the outcome definition (femoral neck DXA T-score ≤ -2.5) does not fully align with clinical decision-making, which primarily relies on fragility fractures and FRAX-estimated 10-year probabilities. Future research should integrate broader metabolic and behavioral determinants, validate DI-GM across diverse populations and dietary contexts, include osteopenic individuals, and align outcomes with fracture risk to enhance clinical and public health utility.