Pharmacological Agents for Soft Tissue and Articular Injections: From Mechanisms to Clinical Applications

Soft tissue and intra-articular injections are common treatments for musculoskeletal disorders, especially chronic tendinopathies and osteoarthritis. In this structured narrative review, receptor-level molecular mechanisms are combined with clinical evidence from various studies for the most common injectable treatments, such as corticosteroids, hyaluronic acid, platelet-rich plasma, and local anesthetics. When combining mechanistic pathways with the results of randomized controlled trials, systematic reviews, and network meta-analyses, clear differences between injectable drugs regarding rapidity of action, duration of action, systemic effects, and safety can be appreciated. Corticosteroids alleviate symptoms rapidly but with only short-term duration. Hyaluronic acid exerts longer-lasting biomechanical and anti-inflammatory effects. Platelet-rich plasma showed the most consistent long-term effect on function and regeneration. Local anesthetics remain useful for diagnostic and interventional purposes but prove harmful to cartilage after excessive administration. A mechanism- and phenotype-based framework for selecting injectables is hereby proposed, wherein treatment could be more individualized and clinical decisions could be optimized in musculoskeletal care.