Long-Term Osteoporosis Risk in Colorectal Cancer Survivors: A Nationwide Longitudinal Cohort with up to 16 Years of Follow-Up

<b>Background/Objectives:</b> Colorectal cancer (CRC) survivors may face long-term health consequences, yet the relationship between CRC and osteoporosis remains underexplored, particularly in Asia. We conducted a nationwide, retrospective longitudinal cohort study with matched controls using the Korean National Health Insurance Service-National Sample Cohort (2005-2019) to assess whether CRC increases osteoporosis risk or not. <b>Methods:</b> We identified 8733 CRC patients and 34,932 matched controls (1:4 ratio) based on age, sex, income, residence, and index date, excluding individuals with pre-existing osteoporosis. Osteoporosis was defined via ICD-10 codes (M80-M82) plus confirmatory bone imaging claims. Propensity score overlap weighting was applied, and adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated using Cox proportional hazards models, with subgroup analyses based on demographic and clinical factors. <b>Results:</b> With up to 16 years of follow-up, osteoporosis incidence rates were 13.80 and 14.30 per 1000 person-years in CRC and control groups, respectively. Adjusted Cox models revealed no significant association between CRC and osteoporosis (HR = 0.95; 95% CI = 0.87-1.04). Subgroup analysis showed a slightly lower risk among CRC survivors aged ≥65 years (adjusted HR = 0.84; 95% CI = 0.75-0.95), though no associations were observed by sex, income, region, or comorbidities. <b>Conclusions:</b> These findings suggest CRC may not be an independent risk factor for osteoporosis in the Korean population. The unexpected age-specific variation warrants cautious interpretation, possibly reflecting competing mortality risks or detection biases.