Objective:
To investigate whether bone mineral density (BMD) is associated with age-related macular degeneration (AMD) and to explore possible causal, molecular, and experimental links.
Approach:
- Human cohorts: Analyzed UK Biobank (275,752 participants), NHANES (3,425), and a Tianjin hospital cohort (1,000), comparing BMD and AMD status.
- Additional analyses: Used machine learning, Mendelian randomization, proteomic and metabolomic profiling, and a glucocorticoid-induced low-BMD rat model.
Key Findings:
- Across all three cohorts, participants with AMD were older and had lower BMD than those without AMD.
- Higher BMD was associated with lower AMD incidence in UK Biobank (adjusted hazard ratio 0.89); inverse associations were also observed in NHANES and Tianjin.
- Age and BMD were repeatedly important features in machine-learning models, but the added predictive value of BMD remains uncertain and the models lack external validation.
- Mendelian randomization results were consistent with a modest contribution of higher BMD to lower AMD risk, with no strong evidence of reverse causality.
- GZMA, NELL1, and COL2A1 were identified as potential molecular intermediates; analyses also implicated extracellular matrix remodeling, lipid transport, amino acid metabolism, and inflammation.
- Low-BMD rats showed outer retinal thinning, narrower retinal vessels, and delayed visual-spatial performance, but did not develop hallmark features of human AMD.
Interpretation:
The authors describe BMD as a possible marker of systemic biological aging associated with retinal vulnerability, rather than an established standalone AMD biomarker.
Limitations:
- AMD ascertainment and BMD measurement differed between cohorts.
- Residual confounding may remain.
- Predictive analyses were exploratory, conducted separately in heterogeneous cohorts, and not externally validated.
- The animal model did not reproduce hallmark features of human AMD.
Conclusion:
The findings support further investigation of a possible bone–eye association, but the authors characterize it as a hypothesis requiring caution.
Sources:
This content is an AI-generated, fully rewritten summary based on a published scholarly article. It does not reproduce the original text and is not a substitute for the original publication. Readers are encouraged to consult the source for full context, data, and methodology.
