Safety of Intra-articular Platelet Rich Plasma Injections for Large Joint Osteoarthritis

A Review Article

Yu M. Chiu, DO; Daniel Wang, BS; Zachary McCormick, MD; Sudhir Diwan, MD; Kenneth D. Candido, MD; George C. Chang Chien, DO


Curr Orthop Pract. 2022;33(5):480-486. 

In This Article

Abstract and Introduction


Platelet-rich plasma (PRP) use in intraarticular injections is thought to be potentially efficacious in the treatment of osteoarthritis (OA) and as an alternative to corticosteroid injections. However, little is known about the safety of PRP usage in the treatment of large joint osteoarthritis. In the 21 identified studies, there were primarily minor adverse effects include pain, redness, swelling, nausea, and dizziness. The limitations of this review include the relative paucity of well-designed studies that describe detailed adverse effects using safety as an outcome measure. Intraarticular injection of platelet-rich plasma has low risk of morbidity. This review describes the evidence for the short-term safety of intraarticular PRP injections and its derivations in the treatment of large joint OA (knee, hip, shoulder). Further investigation is needed to determine the short-term safety of PRP for use in the management of OA in the hip and shoulder, as well as the documentation of long-term safety in the shoulder, hip and knee.


Osteoarthritis (OA) is the most common cause of chronic pain and disability affecting an estimated 650 million people worldwide, or about 15% of all people in the world.[1] In North America and Europe, structural OA of the hands is reported in approximately 60% of adults who are age 65 and older, of the knee in 33%, and of the hip in 5%. OA is a complex disease involving all tissue components in the joint that results from a combination of risk factors, the most important being increasing age and obesity.[1] Current management of OA includes conservative therapies that are nonpharmacological including physical therapy, diet and exercise, weight loss, topical thermal and cryotherapy, and pharmacological including NSAIDs, opioid medications, and topical ointments such as lidocaine and capsaicin. When conservative therapy fails to alleviate symptoms of OA, a minimally invasive injection including viscosupplementation (VS) or corticosteroids can be used. With the different modalities offered in OA treatment, it is important to note that if all of these fail in providing relief, or if OA is severe enough, then arthroplasty is a common option.[2]

The American Academy of Orthopaedic Surgeons (AAOS) and American College of Rheumatology (ACR) formed national recommendations for using nonpharmacologic and pharmacologic therapies in osteoarthritis of the hand, hip, and knee that advised that intraarticular corticosteroid injections (CS) be administered no more than every 3 mo for patients with osteoarthritis whose symptoms were not controlled with full-dose acetaminophen. Furthermore, the national clinical guideline for care and management in adults from the United Kingdom's National Collaborating Centre for Chronic Conditions recommends intraarticular CS combined with weight loss and exercise for relieving pain in patients with osteoarthritis. It is important to note that within the ACR schema, there are only VS and CS provisions and no provisions for the role of regenerative medicine therapies such as platelet-rich plasma (PRP) therapy.

VS is a therapeutic modality where a solution of viscoelastic material is injected into the intraarticular space of the joint. The Food and Drug Administration (FDA) approved hyaluronic acid (HA) in the 1970s for use in eye surgeries and in 2007 for the treatment of knee OA. Although somewhat controversial, studies demonstrated improved duration pain relief and functional outcomes as compared to those of corticosteroid injections.[3] Although VS is still widely utilized in treating knee OA, the AAOS guidelines do not recommend that use. Treatment-related adverse effects have been well-documented, including septic arthritis, pseudoseptic reaction, and anaphylactic shock.[3]

Intraarticular CS has a well-documented history of systemic effects that includes acute changes in endocrine, metabolic, inflammatory markers and cytokines, hematologic, and vascular systems. Such serious side effects as suppression of the hypothalamic-pituitary-adrenal (HPA) axis, causing Cushing's Syndrome[4] and triggering of sickle cell crisis,[5] have been reported after a single injection. Importantly, intraarticular CS injections are also thought to have a destructive effect on soft tissues such as cartilage and tendon.[6]

PRP therapy has become a popular treatment in orthopaedic and sports-related injuries including osteoarthritis, tendinopathy, and muscle and ligamentous injuries.[7] Adverse effects from PRP injections include local pain, infection, allergic reaction, blood clot, and skin discoloration.[8]

PRP injections potentially have many advantages compared with VS and CS. Numerous studies and systematic reviews have sought to establish PRP's efficacy in the treatment of OA. Although many trials have demonstrated benefits in pain relief and functional outcomes, conflicting data exists.

At least seven studies have been performed comparing PRP to VS in treating knee OA. In three out of seven manuscripts, PRP was found to be superior to VS in pain relief and functional outcomes, and noninferior in one study.[9–15] To date, no review paper has sought to quantify the safety of intraarticular PRP in multiple large joints for osteoarthritis. This study sought to conduct a narrative review of such literature.