Role and Effectiveness of Intra-articular Injection of Hyaluronic Acid in the Treatment of Knee Osteoarthritis: A Systematic Review

Abstract

Osteoarthritis (OA) is a degenerative joint disease that causes persistent joint pain and stiffness of mainly the large peripheral weight-bearing joints. It is a leading cause of functional disability and poor quality of life. Various modalities of therapy are recommended by different research organizations at different stages of OA including non-pharmacological, pharmacological, and surgical interventions. Intra-articular injections of hyaluronic acid (HA) is widely used for over three decades in the treatment of OA. However controversies exist regarding its safety and efficacy, the number of injections and courses, type of preparation, duration of its effects, and combining it with other drugs or molecules. This study aimed to review the most recent data available in the published literature to address these. Electronic databases like Medline, Embase, ProQuest, and Google Scholar were searched for articles using keywords, intraarticular injections, hyaluronic acid, and osteoarthritis knee. The review was carried out as per PRISMA guidelines. Thirty-eight randomized control trials (RCTs) investigating the efficacy and safety of intra-articular injection of HA were included in the systematic review. Out of the 38 studies, 22 (57.9%) were double-blind, eight (21%) single-blind, three (7.9%) non-blind, four (10%) with simple randomization, and one (2.7%) was open-labeled. Total 5,025 patients were included in these studies. The mean age of the patients was 60.28 years and the osteoarthritis grade of the knee joint was 1 to 3. HA was studied as a test preparation in 19 (50%) while in another 19 (50%) it was studied as a control. In 24 (63.2%) studies, HA was used as high molecular weight preparation in eight (21%) as low molecular weight preparation while in six studies the information was not available. HA was used as a standalone preparation in 31 studies, in two studies it was injected with platelet-rich plasma (PRP) and with either low-level laser therapy (LLLT), triamcinolone (TA), betamethasone (CS), poly deoxyribonucleotide (PDRN) or dexamethasone (DX) in one study each. In the majority of the studies, HA was given as a single injection (52.6% studies) or weekly three injections (28.9% studies). In 13.2 %, it was given as weekly 5 injections and in 5.3% as weekly two injections. IA-HA injections have a limited role in the treatment of knee osteoarthritis in those patients who do not have sufficient pain relief with topical or oral medication and physical therapy. It is safe and effective except for minor side effects such as local pain and swelling lasting for a few days. Severe allergic reactions are extremely rare. They provide adequate pain relief and functional improvement for up to six months irrespective of a number of injections and type of preparations used. The combination formulations with corticosteroids or PRP or MSCs show better results than HA alone. Combining HA with newer molecules such as peptides or diclofenac for sustained and disease-modifying effects...

Thermo-Responsive Hyaluronan-Based Hydrogels Combined with Allogeneic Cytotherapeutics for the Treatment of Osteoarthritis

“…However, based on the retained endpoints and readouts for the rat ACLT-hMnx model, functional or efficacy-related data were found to be tendential at best ( Figure 3 , Figure 5 , and Figure 6 ). However, such results should be put into perspective from an efficacy point of view, as products similar (i.e., rheology-wise, e.g., Ostenil, TRB Chemedica, Switzerland) to the cell-free HA-based formula used herein (i.e., assessed as non-different from PBS controls in histology, Figure 5 and Figure 6 ) are routinely and successfully used in clinical practice for viscosupplementation applications [ 17 , 63 , 64 , 65 , 66 , 67 , 68 , 69 ]. Furthermore, it appears evident that many of the patient-reported scored outcomes widely used in human medicine are inapplicable in animal models of OA, which does not help to bridge the divide between preclinical efficacy evaluation and clinical efficacy studies.…”

Protecting the regenerative environment: selecting the optimal delivery vehicle for cartilage repair—a narrative review

“…HA may also provide a protective milieu for the cells in the damaged joint surface environment and ensure cells remain localized to cartilage injury ( Li et al, 2015b ; Campbell, 2020 ). HA is used clinically to treat OA via intra-articular application ( Chavda et al, 2022 ). For OA, vehicles such as PRP and HA may represent a compromise between form and function, with custom and commercial versions of each being developed towards regenerative optimization ( Gato-Calvo et al, 2019 ; Chavda et al, 2022 ).…”

Healthy and Osteoarthritis-Affected Joints Facing the Cellular Crosstalk

“…Interestingly, intra-articular lubricin injections into OA mouse models downregulated the inflammatory environment and alleviated pain [ 153 ]. Intra-articular hyaluronan injections may also provide pain relief and improve joint function [ 154 ]. Noteworthily, the diminished hyaluronan synthesis by FLSs is attributable to the pro-inflammatory microenvironment in OA, which induces the depolymerization of high molecular weight hyaluronan into small oligosaccharides [ 155 ].…”