Background/Objectives: Lumbar degenerative disease is a common age-related condition, with epidural steroid injection (ESI) being a widely employed conservative treatment approach. However, the potential effect of ESI on osteoporosis and fracture risk remains unclear. This study investigated the risk of osteoporotic vertebral compression fractures (OVCFs) in patients with lumbar degenerative disease who underwent ESI treatment. Methods: A cohort of 64 patients who received ESI treatment and a control group of 256 patients were included in this study. Demographic data, clinical characteristics, and follow-up information were collected. Cox proportional hazards models were used to analyze risk factors for OVCF, and subgroup analyses were conducted. Results: OVCF was more common in the ESI group than in the control group (hazard ratio [HR]: 3.49, 95% confidence interval [CI]: 1.06-11.43, p = 0.039). After confounding factors were adjusted for, ESI remained an independent risk factor for OVCF (HR: 4.60, 95% CI: 1.01-20.89, p = 0.048). In a subgroup analysis, lower socioeconomic status was associated with higher OVCF risk (HR: 11.82, 95% CI: 1.06-131.26, p = 0.044). The ESI group had improved short-term pain relief, with nonsignificant long-term effects. Conclusions: Patients with lumbar degenerative disease receiving ESI treatment are at an increased risk of OVCF, particularly those with lower socioeconomic status. These findings underscore the importance of regular bone density monitoring and fracture prevention following ESI treatment. Clinicians should carefully weigh the short-term benefits of ESI against the long-term risks and develop individualized follow-up plans for high-risk patients.
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