Osteoporosis risk in alpha and beta thalassemia: An age- and sex-specific retrospective cohort study

RATIONALE: Differential skeletal risks between alpha- and beta-thalassemia subtypes remain unclear. MAIN RESULT: Beta-thalassemia correlates with higher fracture risk than alpha-thalassemia. Notably, males aged 18-50 with beta-thalassemia show a 14-fold increase in osteoporosis. SIGNIFICANCE: Identifies a notably elevated osteoporosis risk in young males, supporting consideration of earlier skeletal surveillance. PURPOSE: The differences in osteoporosis and fracture risk between alpha- and beta-thalassemia subtypes, and how these differences vary by age and sex, remain poorly understood. We conducted a large-scale analysis to characterize these risks and guide risk-stratified protocols. METHODS: This retrospective cohort study used the TriNetX health research network. Patients with alpha- and beta-thalassemia (identified by ICD-10 codes) were matched 1:1 with non-anemic controls by age, sex, race, and comorbidities (chronic kidney disease, diabetes mellitus, rheumatoid arthritis, malnutrition, and endocrine dysfunction) using propensity scores. We assessed the risk of osteoporosis, fractures, and mortality from Kaplan-Meier analyses. RESULTS: Beta-thalassemia patients have a significantly greater risk of osteoporosis (HR = 1.26, 95% CI: 1.11-1.43) than alpha-thalassemia patients. Within the beta-thalassemia group, males demonstrated a risk of osteoporosis that was more than three times higher than that of controls (HR = 3.28, 95% CI: 2.51-4.28), which was notably higher than that observed in females (HR = 1.42, 95% CI: 1.26-1.60). Young males (aged 18-50) demonstrated a markedly elevated risk of osteoporosis (HR = 13.97, 95% CI: 7.30-26.73) and mortality (HR = 6.31, 95% CI: 3.62-11.01) compared to matched controls. CONCLUSION: Beta-thalassemia is associated with worse skeletal outcomes than alpha-thalassemia. Young male patients demonstrate substantially elevated risk of osteoporosis and mortality. These findings highlight the need for age- and sex-specific risk assessment in thalassemia patients.