Corticosteroids, hyaluronic acid, platelet-rich plasma, and cell-based therapies for knee osteoarthritis - literature trends are shifting in the injectable treatments' evidence: a systematic review and expert opinion.

Introduction: The aim of this systematic review was to quantify the data available on corticosteroids (CS), hyaluronic acid, (HA), platelet-rich plasma (PRP), and cell-based therapies for knee osteoarthritis (OA) treatment.

Methods: A literature search was conducted on PubMed, Cochrane, and Web of Science according to the PRISMA guidelines. Inclusion criteria: clinical studies of any level of evidence, written in English, evaluating the intra-articular use of CS, HA, PRP, or cell-based therapies for knee OA treatment.

Results: The initial search identified 17,415 records. A total of 766 studies from 1959 were included. Of these, 401 were randomized controlled trials (RCTs), 110 comparative studies, and 255 case series, for a total of 75,834 patients. (11,245 treated with CS, 40,862 with HA, 16,174 with PRP, and 7,553 with cell-based therapies). The number of placebo-controlled RCTs remains limited and a negligible percentage of studies investigated possible disease-modifying effects of these treatments for knee OA.

Conclusions: The evidence on injective knee OA treatments is increasing at different speeds with a more rapidly growing literature focusing on orthobiologics. Currently, HA has the largest evidence, followed by PRP that recently surpassed the number of studies evaluating CS. Cell-based therapies are also growing rapidly, although the number of studies is still lower. The rapid literature shift toward orthobiologics urges an update in societies' guidelines to align with the new body of evidence on knee OA treatments.

Protocol Registration: www.crd.york.ac.uk/prosperoi dentifier is CRD42024592972.