Dose–Response Meta-Analysis of Corticosteroid Effects in SARS Outbreak: A Model for Risk Stratification and Screening Strategy for Osteonecrosis of Femoral Head Post-Corticosteroid Therapy for COVID-19

Corticosteroids (CS) have been used in the management regimens for COVID-19 disease to mitigate the cytokine storm and ill effects of the pulmonary inflammatory cascade. With the rampant use of CS, clinicians started reporting the occurrence of osteonecrosis of the femoral head (OFH). In this systematic review, we aim to analyze the literature and identify the definitive cumulative dose and duration of CS needed for the development of OFH based on the SARS model and generate a risk-based screening recommendation for OFH in convalescent COVID-19 patients to facilitate early identification and management. An electronic database search was conducted until December 2022 in PubMed, Web of Science, Embase, and CNKI (China Knowledge Resource Integrated Database). Studies involving CS therapy and osteonecrosis data in SARS patients were included. Three authors independently extracted the data from the included studies and a dose–response meta-analysis was performed for various doses and duration of CS utilized in the included studies. We selected 12 articles with 1728 patients in the analysis. The mean age was 33.41 (±4.93) years. The mean dosage of CS administered was 4.64 (±4.7) g which was administered for a mean duration of 29.91 (±12.3) days. The risk of osteonecrosis increases at pooled OR of 1.16 (95% CI 1.09–1.23, p < 0.001) per 2.0 g increase in the cumulative dose of CS usage. Similarly, the risk increases at pooled OR of 1.02 (95% CI 1.01–1.03, p < 0.001) per 5 days of increase in the cumulative duration of CS usage. A cumulative dosage of 4 g and a duration of 15 days were determined as the critical cut-off for the non-linear dose–response relationship observed. Appropriate and frequent screening of these individuals at regular intervals would help in the identification of the disease at an early stage in order to treat them appropriately.