Hemolytic anemia (HA) renders erythropoietic stress on the bone marrow and has been linked to osteoporosis. In this nationwide retrospective cohort study, we examined this correlation by utilizing the Taiwan National Health Insurance Research Database (NHIRD). We identified two cohorts, matching population with and without HA in a 1:4 ratio. A total of 2242 HA patients and 8968 non-HA patients were enrolled. Patients with HA had a significantly higher cumulative incidence (log-rank test p = 0.0073), higher incidence density (5.11 vs. 3.76 per 1000 persons-years), and a 1.31-fold risk of developing osteoporosis than non-HA patients (aHR = 1.31, 95% C.I. 1.04-1.63, p = 0.01). After adjusting for age, sex, and comorbidities, patients with factors including female (aHR = 2.57, 95% C.I. 2.05-3.22, p < 0.001), age > 65 (aHR = 9.25, 95% C.I. 7.46-11.50, p < 0.001), diagnosis of cholelithiasis (aHR = 1.76, 95% C.I. 1.20-2.58, p = 0.003) and peptic ulcer disease (aHR = 1.87, 95% C.I. 1.52-2.29, p < 0.001) had significantly higher risk of osteoporosis. We propose that this correlation may be related to increased hematopoietic stress, increased consumption of nitric oxide (NO) by hemolysis, and the inhibitory effects of iron supplements on osteogenesis through the receptor activator of nuclear factor κB ligand (RANKL)/Osteoprotegerin pathway and the Runt-related transcription factor 2 (RUNX2) factor. Our findings suggest that patients with hemolytic anemia are at a higher risk of developing osteoporosis, and it would be in the patient's best interest for physicians to be aware of this potential complication and offer preventative measures.
Keywords: hematopoietic stress; hemolytic anemia; national health insurance research database; osteoporosis.