Diarthrodial joints are well suited to intra-articular injection, and the local delivery of therapeutics in this fashion brings several potential advantages to the treatment of a wide range of arthropathies. Possible benefits over systemic delivery include increased bioavailability, reduced systemic exposure, fewer adverse events, and lower total drug costs. Nevertheless, intra-articular therapy is challenging because of the rapid egress of injected materials from the joint space; this elimination is true of both small molecules, which exit via synovial capillaries, and of macromolecules, which are cleared by the lymphatic system. In general, soluble materials have an intra-articular dwell time measured only in hours. Corticosteroids and hyaluronate preparations constitute the mainstay of FDA-approved intra-articular therapeutics. Recombinant proteins, autologous blood products and analgesics have also found clinical use via intra-articular delivery. Several alternative approaches, such as local delivery of cell and gene therapy, as well as the use of microparticles, liposomes, and modified drugs, are in various stages of preclinical development.

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Progress in intra-articular therapy

Results: Treatment with a local injection of ACP had a significant effect shortly after the final infiltration and a continuously improving sustained effect up to 24 weeks (WOMAC score, 65.1 and 36.5 in the HA and ACP groups, respectively; P \ .001), where the clinical outcomes were better compared with the results with HA. In the HA group, the worst results were obtained for grade III gonarthrosis, whereas the clinical results obtained in the ACP group did not show any statistically significant difference in terms of the grade of gonarthrosis. The mean WOMAC scores for grade III gonarthrosis were 74.85 in the HA group and 41.20 in the ACP group (P \ .001). Conclusion: Treatment with ACP showed a significantly better clinical outcome than did treatment with HA, with sustained lower WOMAC scores. Treatment with HA did not seem to be effective in the patients with grade III gonarthrosis.

/pdf/comparison-between-hyaluronic-acid-and-platelet-rich-plasma-1jvxrafgew.pdf

Comparison Between Hyaluronic Acid and Platelet-Rich Plasma, Intra-articular Infiltration in the Treatment of Gonarthrosis

Platelet rich plasma (PRP) is a powerful new biologic tool in sports medicine. PRP is a fraction of autologous whole blood containing and increased number of platelets and a wide variety of cytokines such as platelet derived growth factor (PDGF), vascular endothelial growth factor (VEGF) and transforming growth factor beta-1 (TGF-B1), fibroblast growth factor (FGF), Insulin-like growth factor-1 (IGF-1) among many others. Worldwide interest in this biologic technology has recently risen sharply. Basic science and preclinical data support the use of PRP for a variety of sports related injuries and disorders. The published, peer reviewed, human data on PRP is limited. Although the scientific evaluation of clinical efficacy is in the early stages, elite and recreational athletes already use PRP in the treatment of sports related injuries. Many questions remain to be answered regarding the use of PRP including optimal formulation, including of leukocytes, dosage and rehabilitation protocols. In this review, a classification for platelet rich plasma is proposed and the in-vitro, preclinical and human investigations of PRP applications in sports medicine will be reviewed as well as a discussion of rehabilitation after a PRP procedure. The regulation of PRP by the World Anti-Doping Agency will also be discussed. PRP is a promising technology in sports medicine; however, it will require more vigorous study in order to better understand how to apply it most effectively.

Sports Medicine Applications of Platelet Rich Plasma

A 67-year-old woman with osteoarthritis of the right knee seeks guidance regarding the possible benefit of hyaluronate injection. Injections of hyaluronate for viscosupplementation have been used in osteoarthritis of the knee, but their efficacy remains uncertain.

https://www.nejm.org/doi/pdf/10.1056/NEJMct1215534?bcsi_scan_43167910db6ab4d9=CZEAv5pJCTivtuC2TcNutMEsAuEEAAAALc85IA==

Viscosupplementation for Osteoarthritis of the Knee

Intra-articular drug delivery has a number of advantages over systemic administration; however, for the past 20 years, intra-articular treatment options for the management of knee osteoarthritis (OA) have been limited to analgesics, glucocorticoids, hyaluronic acid (HA) and a small number of unproven alternative therapies. Although HA and glucocorticoids can provide clinically meaningful benefits to an appreciable number of patients, emerging evidence indicates that the apparent effectiveness of these treatments is largely a result of other factors, including the placebo effect. Biologic drugs that target inflammatory processes are used to manage rheumatoid arthritis, but have not translated well into use in OA. A lack of high-level evidence and methodological limitations hinder our understanding of so-called ‘stem’ cell therapies and, although the off-label administration of intra-articular cell therapies (such as platelet-rich plasma and bone marrow aspirate concentrate) is common, high-quality clinical data are needed before these treatments can be recommended. A number of promising intra-articular treatments are currently in clinical development in the United States, including small-molecule and biologic therapies, devices and gene therapies. Although the prospect of new, non-surgical treatments for OA is exciting, the benefits of new treatments must be carefully weighed against their costs and potential risks. Intra-articular therapies for knee osteoarthritis (OA) are causing excitement among clinicians and patients, but care should be taken when choosing which therapy to use. In this Review, Vangsness and colleagues critically appraise current and future intra-articular therapies for knee OA.

Intra-articular treatment options for knee osteoarthritis

Background: To achieve their potential therapeutic benefit, hyaluronic acid derivatives should be injected directly into the knee joint space and not into the anterior fat pad or the subsynovial tissues. In the absence of a knee effusion, reproducible needle placement into the intra-articular space presents a challenge to the clinician. Methods: The accuracy of needle placement was assessed in a prospective series of 240 consecutive injec- tions in patients without clinical knee effusion. The injections were performed by one orthopaedic surgeon us- ing a 2.0-in (5.1-cm) 21-gauge needle through three commonly employed knee joint portals: anteromedial, anterolateral, and lateral midpatellar. Accuracy rates for needle placement were confirmed with fluoroscopic im- aging to document the dispersion pattern of injected contrast material. Results: Of eighty injections performed through an anterolateral portal, fifty-seven were confirmed to have been placed in the intra-articular space on the first attempt (an accuracy rate of 71%). Sixty of eighty injections per- formed through an anteromedial approach were intra-articular on the first attempt (75% accuracy rate), as were seventy-four of eighty injections performed through a lateral midpatellar portal (93% accuracy rate). Conclusions: Using real-time fluoroscopic imaging with contrast material, we demonstrated the difficulty of ac- curately placing a needle into the intra-articular space of the knee when an effusion is not present. This study revealed that a lateral midpatellar injection (an injection into the patellofemoral joint) was intra-articular 93% of the time and was more accurate than injections performed by the same orthopaedic surgeon using either of the other two portals. This study highlights the need for clinicians to refine injection techniques for delivering intra- articular therapeutic substances that are intended to coat the articular surfaces of the knee joint.

Bradley M. Thomas

Papers

Accuracy of Needle Placement into the Intra-Articular Space of the Knee