From Physicochemical Properties to Rehabilitation Outcomes: Understanding Corticosteroid Injection Adverse Effects

Corticosteroid injections (CSIs) are widely used in Physical and Rehabilitation Medicine, but their safety profile is strongly influenced by the formulation-specific chemical structure and physicochemical properties of each molecule, as well as by injection technique and dosing strategy. Particulate corticosteroids such as triamcinolone acetonide and methylprednisolone acetate exhibit low aqueous solubility, microcrystal formation, and prolonged intra-articular residence, which translate into sustained anti-inflammatory effects but also higher risks of chondrotoxicity, calcifications, tendinopathy, cutaneous and muscular atrophy, osteonecrosis, nerve injury, infection, and post-injection flare, especially with repeated or high-dose use. In contrast, more soluble preparations like betamethasone and dexamethasone sodium phosphate provide rapid onset and shorter duration of action, with reduced local depot-related complications but a greater propensity for transient systemic effects such as glycemic spikes. Across adverse events, less soluble, longer-acting formulations and inaccurate extra-articular delivery consistently emerge as key drivers of local tissue damage. Ultrasound guidance significantly improves injection accuracy, optimizes drug deposition of both particulate and non-particulate agents, and may enhance clinical outcomes while limiting complications, thereby representing a relevant component of CSI practice. In conclusion, this narrative review proposes a formulation-oriented framework for corticosteroid selection, integrating pharmaceutical formulation, physicochemical properties, imaging guidance, and individualized rehabilitation strategies to optimize molecule selection, minimize adverse effects, and advance a precision rehabilitation paradigm.