Comparative Short-Term Clinical Outcomes of Hybrid Hyaluronic Acid and Platelet-Rich Plasma Injections in Knee Degenerative Conditions: An Exploratory Real-World Retrospective Study

Background and Objectives: Knee osteoarthritis (KOA) and other degenerative chondropathies are major causes of pain and disability. When core conservative treatments are insufficient, intra-articular hyaluronic acid (HA) and platelet-rich plasma (PRP) are commonly used as adjunctive options, although evidence remains difficult to interpret because of heterogeneity in patients, products, preparation protocols, and treatment schedules. This exploratory retrospective study described short-term clinical outcomes after two standardized intra-articular protocols, hybrid HA and autologous PRP, in a real-world outpatient physiatry setting. Materials and Methods: This monocentric retrospective study included 40 treated knees (19 HA, 21 PRP) from 31 unique patients at the Policlinico di Bari between October 2022 and November 2024. The HA group received two injections of a hybrid high-/low-molecular-weight HA formulation, whereas the PRP group received three injections of autologous PRP. Outcomes were pain intensity, assessed by the Numerical Rating Scale (NRS), and function, assessed by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), from baseline to end-of-cycle follow-up. Results: Both groups showed short-term clinical improvement. Mean NRS scores decreased from 6.26 to 2.26 in the HA group and from 6.76 to 2.29 in the PRP group, with no significant between-group difference in change from baseline (p = 0.509). WOMAC improved by 25.42 ± 20.39 points in the HA group and 20.19 ± 16.18 points in the PRP group (p = 0.372). In the main regression analysis, treatment type was not a significant predictor of outcome; unadjusted and age-/sex-adjusted WOMAC sensitivity models suggested a possible HA advantage that was not retained after full adjustment. Conclusions: In this small exploratory cohort, both protocols were associated with short-term improvements, without definitive fully adjusted evidence of between-group superiority. These findings should not be interpreted as evidence of equivalence or definitive comparative efficacy.