<![CDATA[Knee osteoarthritis is a chronic degenerative joint disorder involving articular cartilage, subchondral bone, synovium, and periarticular structures. Intra-articular hyaluronic acid (IAHA) is widely used as a viscosupplementation therapy; however, its clinical effectiveness remains controversial with heterogeneous outcomes across studies. Vitamin D deficiency has been implicated in musculoskeletal dysfunction, inflammation, and oxidative stress, which may influence therapeutic response in osteoarthritis patients. This literature review aims to evaluate the effectiveness of intra-articular hyaluronic acid in patients with knee osteoarthritis and concomitant vitamin D deficiency or insufficiency based on recent evidence from 2021–2026. A systematic literature review was conducted using PubMed, PubMed Central, Google Scholar, ScienceDirect, Cochrane Library, BMJ, Frontiers, MDPI, and clinical guidelines. Eligible studies included randomized controlled trials, systematic reviews, meta-analyses, cohort studies, and consensus reports. Narrative synthesis was applied due to limited direct evidence evaluating combined IAHA and vitamin D intervention. Results of the study show that IAHA demonstrates small to moderate effects in reducing pain and improving functional outcomes in knee osteoarthritis, particularly in mild-to-moderate disease stages. However, pooled evidence suggests limited clinical superiority compared to placebo in several meta-analyses. Vitamin D deficiency is consistently associated with increased pain severity, reduced functional status, and lower quality of life. Emerging evidence indicates that vitamin D supplementation combined with IAHA may reduce synovial oxidative stress and improve clinical outcomes, although the evidence remains preliminary and non-conclusive. IAHA should not be recommended as a universal treatment for knee osteoarthritis. In patients with vitamin D deficiency or insufficiency, correction of vitamin D status may be considered as part of a multimodal approach and may enhance clinical response to IAHA. High-quality randomized controlled trials are required to confirm the synergistic effect.]]>
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