Background: Knee osteoarthritis (KOA) is a common degenerative and progressive joint disorder that negatively influences patients’ quality of life. Intra-articular therapies, such as hyaluronic acid (HA) and platelet-rich plasma (PRP), have garnered attention for their potential to manage osteoarthritis OA symptoms effectively. This systematic review aims to identify the effectiveness and safety of HA and PRP treatment modalities in treating KOA. Methods: A literature search was conducted across MEDLINE (PubMed), Web of Science Core Collection, and Science Direct Collection Elsevier. Twenty-three randomized controlled trials, cohort studies, and observational studies were included in the review. The selection criteria focused on studies published in English within the last 10 years, involving subjects with KOA treated with intra-articular injections of HA or PRP and reporting on pain, function, or overall treatment efficacy outcomes. Results: The analysis showed that both HA and PRP significantly improve functionality and reduce pain in KOA patients. High molecular weight HA consistently reduced pain and improved joint mobility in various studies. PRP had better long-term outcomes when combined with HA, leading to greater pain reduction and functional improvement. Both therapies had generally favorable safety profiles, with only minor adverse events reported. However, there were potential biases identified across the studies, such as selection, performance, detection, and reporting biases, which impacted the reliability of the results. Conclusions: Intra-articular treatments with HA and PRP show promise in managing knee osteoarthritis, with personalized treatment plans and further research needed to confirm these findings.

Knee osteoarthritis (OA) is a complex condition with varying pain, functional limitations, and structural changes. Traditional classification using radiographic grades may not fully reflect individual patient experiences. This study aimed to establish WOMAC score cut-offs for KL grades and identify knee OA phenotypes through cluster analysis in a cohort of 99 adults, examining functional and radiological status, factors such as age, sex, body mass index (BMI), comorbidities, and psychological status. Receiver operating characteristic (ROC) analysis helped establish WOMAC cut-off scores related to KL grades, and cluster analysis identified phenotypic subgroups. The analysis showed that higher WOMAC scores correlated with advanced KL grades, leading to a five-tier classification of symptomatic severity: minimal or no symptoms (≤24), mild (25–41), moderate (42–69), severe (70–86), and extreme (≥87). Cluster analysis identified four distinct phenotypic groups: (1) younger patients exhibiting minimal symptoms and low KL grades; (2) individuals with moderate disease are characterized by functional deficits; (3) patients presenting with moderate-to-severe symptoms and significant joint narrowing; and (4) a subgroup experiencing severe pain, high levels of disability, advanced KL grades, elevated psychological distress, and an increased BMI. The study supports WOMAC cut-offs as key indicators of knee OA severity and shows that cluster analysis can reveal distinct phenotypes, underscoring the need for personalized management strategies in knee OA treatment.