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

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. PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.