Biologics for Advanced Hip and Knee Arthritis
Position of the American Association of Hip and Knee Surgeons Position StatementsAn increasing number of facilities and physicians are offering intra-articular injections of stem cells and/or platelet-rich plasma (PRP) as a non-surgical treatment of advanced hip and knee osteoarthritis (OA). Administration of PRP injections in the United States increased more than 400% from 2010 to 2020. The global market for biologic injections is expected to become a multi-billion-dollar entity within the near future.
There are more than 40 commercial PRP systems in existence; many of these systems were brought to market via the Food and Drug Administration (FDA) 510(k) pathway based on prior clearance of equivalent devices designed to mix PRP with bone graft.
As such, isolated PRP injections into a hip or knee joint are considered “off-label” by the FDA. Further, PRP and bone marrow aspirate concentrates (BMAC) are exempt from FDA regulation under Title 21, Part 1271 of the Code of Federal Regulations (21 CFR 1271). As a result, there is significant variability in the indications for use, preparation, processing, and administration of biologic treatments for the treatment of hip and knee OA across providers and practices.
As the popularity of biologic injections has increased, so has the breadth of patient education materials available online. Readily available information on biologic injections accessed via internet search engines is often targeted directly at the lay public suffering from hip or knee pain. However, this information is often incomplete and may be misleading to patients, with an emphasis on unsubstantiated benefits and a lack of information on potential risks or alternative treatments. Direct-to-consumer marketing of BMAC as a “stem cell” therapy may further patient confusion. While BMAC preparations usually contain extremely low concentrations (<0.01%) of mesenchymal stem cells (MSCs), such concentrations are much lower than those found in mesenchymal stem cells preparations that utilize culture expansion (e.g., adipose tissue-derived MSCs, umbilical cord blood-derived MSCs). However, autologous blood products such as BMAC are not subject to FDA regulation, whereas stem cell preparations using culture expansion are subject to FDA regulation under 21 CFR 1271. Biologic injections are often not covered by insurance companies, which may result in thousands of dollars of out-of-pocket costs for patients.
Osteoarthritis is a slowly progressive degenerative disorder that involves damage to joint cartilage, structural changes in bone, and inflammation of the soft tissues around the joint. Advanced arthritis involves complete loss of cartilage surface and exposure of subchondral bone (so-called “bone-on-bone arthritis”). Presently, there is no curative treatment for advanced hip and knee OA. Counter to claims made by individual providers or practices, biologic injections have not been shown to restore cartilage in hips and knees with OA.
Non-surgical treatments of advanced hip and knee OA are aimed at decreasing joint pain and improving joint function while avoiding the risks associated with total hip and total knee arthroplasty; biologic injections are no different. Recent prospective randomized controlled trials have failed to demonstrate a significant benefit in pain or function of intra-articular PRP injections over intra-articular injections of saline placebo, corticosteroids, hyaluronic acid (HA), or genicular nerve radiofrequency ablation in patients with advanced knee OA. Notably, there is limited evidence suggesting that PRP may be more efficacious than placebo and/or HA injections for the treatment of mild or moderate knee OA. Systematic reviews of level 1 and level 2 randomized controlled trials have demonstrated relatively equal efficacy of PRP and HA injections for patients with advanced hip OA. Studies evaluating the efficacy of mesenchymal stem cells have demonstrated comparable results. While intra-articular injection of culture-expanded MSCs may offer a mild improvement relative to placebo, MSCs derived from multiple tissues sources have not been shown to be superior to corticosteroid injections for the treatment advanced knee OA.
Previous iterations of this position statement questioned the safety of biologic injections. Reported complications of biologic injections have included injection site pain, hematoma formation, aseptic inflammatory response, and intra-articular infection. Recent systematic reviews have demonstrated no difference in the safety profiles of injections of saline placebo and biologics. Modern randomized controlled trials examining the use of PRP and/or mesenchymal stem cells have demonstrated that biologic treatments can be administered without major adverse effects under rigorous safety protocols; however, it is paramount that the safety of biologic treatments be fully established before they can be supported for routine clinical use.
In conclusion, it is our position that biologic therapies, including injections of PRP, BMAC, or mesenchymal stem cells, cannot currently be recommended for the routine treatment of advanced hip or knee OA. This current position is largely unchanged from our prior position statement, published in 2019. A lack of data demonstrating significant improvements over existing non-biologic therapies and high out-of-pocket costs for patients preclude an endorsement of the routine use of biologics for the treatment of advanced hip and knee OA. We continue to encourage rigorous, well-designed clinical trials to further establish the safety, efficacy, and cost-effectiveness of biologic treatments prior to their widespread adoption.
This statement is an expression of the policy of the American Association of Hip and Knee Surgeons. It is not a comprehensive review of the subject nor is it intended as medical advice for the treatment of individual patients.
