article · Aging Clinical and Experimental Research
Hyaluronic acid (HA) is a linear polysaccharide which occurs naturally as a constituent of synovial fluid. The HA concentration in the joint decreases inexorably during the progression of knee osteoarthritis (OA) and so, for nearly five decades, HA has been trialled and used in the treatment of knee OA. There are strong data from clinical trials, meta-analyses and umbrella reviews to support the use of intra-articular hyaluronic acid (IAHA) in the treatment of patients with knee OA, though not in patients with acute, active OA experiencing a flare. The majority of the literature suggests that IAHA has a positive safety profile despite a few meta-analyses suggesting an increased risk of serious adverse effects. Further qualitative analysis integrating patient preferences for multi-modal and/or non-surgical management is required in order to further explore these findings. IAHA has been combined with a number of additional agents, including mannitol, sorbitol, chondroitin sulphate, tranexamic acid, polynucleotides and hybrid IAHA formulations. These show variable performance beyond the baseline effect of their constituents. It is crucial to consider the patient’s preference when considering treatments for knee OA. Specific to IAHA, patients seek minimally invasive, lower-risk, and non-steroidal options with at least moderate efficacy and advantageous safety profiles. Hyaluronic acid is a naturally occurring constituent of synovial fluid and there are strong studies supporting its use in the treatment of osteoarthritis (outside the context of disease flares). The majority of literature supports a highly advantageous safety profile for hyaluronic acid in terms of adverse effect profile. Intra-articular hyaluronic acid (IAHA) can be injected in combination with other agents; including mannitol, sorbitol, chondroitin sulphate, tranexamic acid, polynucleotides and hybrid IAHA formulations, which show potential efficacy beyond their constituents alone.
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DOI: 10.1007/s40520-026-03366-8
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