# Sex-specific association between osteoporosis and cataracts: UK Biobank and Hong Kong Osteoporosis Study

## TL;DR

Osteoporosis is linked to a higher risk of cataracts, especially in women, with five proteins possibly connecting the two conditions.

## Contribution

Identified a sex-specific link between osteoporosis and cataracts and five potential mediating proteins.

## Key findings

- Osteoporosis was associated with increased cataract risk in both UK and Hong Kong cohorts.
- The association was stronger in women compared to men.
- Five proteins (MEPE, GDF15, TCN2, CDCP1, SIGLEC1) were identified as potential mediators.

## Abstract

In two large, ethnically different prospective cohorts from the UK and Hong Kong, osteoporosis was associated with a higher risk of age-related cataracts, particularly in women. Proteomic mediation analysis identified five circulating proteins (MEPE, GDF15, TCN2, CDCP1, SIGLEC1) that may link osteoporosis to cataract development, warranting future mechanistic investigation.

Osteoporosis and cataracts are frequently comorbid age-related conditions. This study aims to investigate the association between osteoporosis and the risk of age-related cataracts in cohorts from the United Kingdom (UK) and Hong Kong.

Prospective cohort studies were conducted in participants aged ≥ 40 years without cataracts at baseline, using data from the UK Biobank (UKB; n = 337,952) and the Hong Kong Osteoporosis Study (HKOS; n = 4,935), with a median follow-up of 13.5 and 18.5 years, respectively. Incident age-related cataracts were identified using International Classification of Diseases (ICD) codes in each cohort, and the associations of bone mineral density (BMD) and osteoporosis with the risk of age-related cataract were analyzed using Cox proportional hazard models, adjusted for demographics, comorbidities, medications, and blood biomarker levels. We also conducted a mediation analysis to explore potential proteins mediating the relationship.

In UKB, osteoporosis was associated with increased cataract risk (HR, 1.16; 95% CI, 1.08–1.25). In HKOS, participants with BMD T-scores between − 2.5 and − 1 (HR, 1.24; 95% CI, 1.05–1.45) and ≤  − 2.5 (HR, 1.34; 95% CI, 1.09–1.66) had higher cataract risk compared to those with T-scores ≥  − 1. Subgroup analyses suggested the relationship was female-specific in both cohorts. Mediation analysis identified five proteins that may mediate this relationship.

Our findings suggest a female-specific association between osteoporosis and incident age-related cataracts. Integrated care is crucial for patients with these conditions. Timely ophthalmic evaluation and intervention may benefit patients with low BMD.

The online version contains supplementary material available at 10.1007/s11657-026-01674-0.