Safety of intra-articular corticosteroid and hyaluronic acid injections: a 14-year population-based cohort study of 404,797 patients

Intra-articular corticosteroid and hyaluronic acid injections are fundamental in managing musculoskeletal pathologies. While their local efficacy is well documented, concerns regarding systemic safety, specifically the risk of acute hospitalization due to infection or vascular events—remain a subject of debate. This study aimed to evaluate long-term utilization trends and the incidence of subsequent hospitalizations in a large-scale general population. We conducted a retrospective, population-based cohort study utilizing data from Clalit Health Services (Israel) between 2010 and 2023. The cohort included all adults (≥ 18 years) who received at least one intra-articular or peri-articular injection. The primary outcome was hospitalization within 30 days post-injection with a principal discharge diagnosis of a systemic/musculoskeletal infection or an acute vascular event. Multivariable logistic regression was used to identify independent predictors of adverse outcomes, adjusting for demographics, diabetes status, and Charlson Comorbidity Index (CCI). The study analyzed 404,797 patients (mean age 55 ± 16 years, 55% female). Over the 14-year period, injection utilization rose significantly, with the standardized frequency doubling from 10.5 to 20.9 injections per 1,000 individuals (a 136% absolute increase). Despite this surge in volume, hospitalization rates remained low and stable throughout the study period. In multivariable analysis, the Charlson Comorbidity Index (CCI) was the sole independent predictor of hospitalization. Notably, diabetes mellitus alone was not associated with an increased risk of hospitalization. Corticosteroid and hyaluronic acid injections remain a safe treatment option regarding the risk of severe adverse events requiring hospitalization. The risk of such events is rare and is primarily driven by the patient's comorbidity burden rather than the injection event itself. These findings support the continued use of these interventions, with an emphasis on individualized risk assessment using validated tools such as the Charlson Comorbidity Index.