In 2009, The New York Times reported that professional football player Hines Ward of the Pittsburgh Steelers underwent platelet-rich plasma (PRP) therapy for a sprained medial collateral ligament. The Times noted that approximately 2 weeks after undergoing this treatment, Mr. Ward—who also underwent rehabilitation and hyperbaric oxygen therapy—went on to help his team win Super Bowl XLIII, making two catches in the National Football League championship game. Mr. Ward credited PRP therapy with helping him recover quickly and get back on the field.

The story, which also focused on other elite athletes who have been treated with PRP, was one of many early media reports on potential benefits of the biologic agent. Despite the increased attention on PRP, however, many questions still remain about its efficacy in various orthopaedic applications.

AAOS Now: To what do you attribute the surge of interest in PRP?

Dr. Hsu: When the media began reporting that many high-profile athletes and celebrities were treated with PRP and had good results, the lay public became widely intrigued by its effects. Much of the curiosity and interest related to PRP stems from the fact that it is derived from a patient’s own blood, making it a safe biologic treatment with regenerative potential for all types of patients, not just athletes.

AAOS Now: Why is it so challenging to determine and compare the efficacy of PRP in various orthopaedic applications?

Dr. Hsu: Orthopaedic conditions vary greatly in terms of associated pathophysiology, anatomic area, healing mechanisms, and natural history. In other words, a patient with lateral epicondylitis has a different course of care and recovery than a patient with Achilles tendonitis, even though both of these conditions involve muscle tendons. Furthermore, more than 40 different formulations of PRP are commercially available, each with different processing techniques, blood volume requirements, additives, and white blood cell (WBC) content. Comparing clinical outcomes from each of these systems can be difficult because the biologic material tested is so different.

AAOS Now: Of all the recent studies on PRP outlined in the review article, are there one or two studies you would highlight as particularly interesting?

Dr. Hsu: Allan K. Mishra, MD, and Terri Pavelko, PAC, PT, have published a series of studies on the use of PRP for treating lateral epicondylitis, with up to 2-year follow-up. They continue to improve the quality of conclusions with each subsequent study design, with longer-term follow-up and better identification of the differences in how patients respond to different formulations, such as formulations with high WBC content. These level I clinical trials have helped set the standards that future PRP trials should follow.

In addition, a recent level I study involving knee osteoarthritis patients from Prof. Fabio Cerza and colleagues is quite intriguing, in my opinion. The study demonstrated benefits of improved pain from PRP injections compared to hyaluronic acid at 24 weeks, which supports the need for further study of this condition.

AAOS Now: In which orthopaedic applications is PRP particularly promising?

Dr. Hsu: Based on the current literature—which has and will continue to grow and change—the most promising applications of PRP seem to involve elbow epicondylitis, osteoarthritis of the knee, and bone-tendon interface healing in anterior cruciate ligament reconstruction surgery. The body of evidence in support of using PRP for these applications is building.

In areas such as bone healing applications, however, the available evidence suggests that PRP is not effective, either alone or as an adjunct to local bone graft. In addition, results of clinical studies on rotator cuff and Achilles tendon repairs have not found significant differences in outcomes with or without the use of PRP. Thus, more research is needed before we can reach definitive conclusions on its use in these applications.

AAOS Now: In the review article, you noted that some studies have indicated that PRP can actually have a detrimental effect.

Dr. Hsu: Yes, that is true. PRP contains a collection of growth factors and substances, many of which have not been well studied. Some of these factors may have an inhibitory effect on tissue healing. For example, because many studies in the spinal fusion literature have concluded that the addition of PRP significantly reduces bone healing rates, it has been postulated that the presence of so many different growth factors in high concentrations prevents a directed bone-forming pathway. This “distracting effect” can also affect other orthopaedic applications, such as muscle and tendon healing.

AAOS Now: What kinds of studies are needed in the future?

Dr. Hsu: Future studies should focus on standardizing PRP formulations. Experts should agree upon the ideal blood volume, WBC count, use of additives (such as thrombin), and surgical techniques before making claims of success or failure in certain applications. There have been attempts at establishing a classification system that would identify factors such as the presence of WBCs, activation with thrombin, and the concentration of platelets above baseline.

In addition, much work still needs to be done to better define the cost-effectiveness of PRP in orthopaedic applications. No clinical studies have attempted to answer this question yet. PRP therapy generally costs more than comparative injection therapies such as corticosteroids, but less than surgical options.

Although there is still a dearth of reliable clinical evidence for the use of PRP in a variety of orthopaedic applications, the body of evidence has grown substantially in the past 3 years. PRP now has clinical support as a legitimate nonsurgical option in some musculoskeletal conditions, such as lateral elbow epicondylitis. It has been very encouraging to see the quality and quantity of research on PRP therapy rise significantly in response to the patient demand for its use in symptomatic diseases. As PRP research moves forward, it is likely that a formal algorithm for its use in orthopaedic patients will be formulated to provide more guidance to orthopaedic surgeons.

Dr. Hsu’s coauthors of “Platelet-rich Plasma in Orthopaedic Applications: Evidence-based Recommendations for Treatment” include Allan K. Mishra, MD; Scott A. Rodeo, MD; Freddie H. Fu, MD; Michael A. Terry, MD; Pietro Randelli, MD; S. Terry Canale, MD; and Frank B. Kelly, MD.

Disclosure information: Dr. Hsu—AONA, Lifenet, Medtronic, Pioneer Surgical, Stryker, Terumo, Zimmer, Baxter; Dr. Mishra—Biomet, ThermoGenesis, BioParadox; Dr. Rodeo—Smith & Nephew, Cayenne; Dr. Fu—Arthrocare, Stryker, SLACK Incorporated, Wolters Kluwer Health – Lippincott Williams & Wilkins;Dr. Terry—Smith & Nephew, Arthrex, Inc., Saunders/Mosby-Elsevier; Dr. Randelli—Biomet, Depuy – A Johnson & Johnson Company, Dr. Canale—Campbell’s Operative Orthopaedics, AAOS Now, Bioworks, Campbell Foundation, OREF; Dr. Kelly—AAOS Now, OREF.

Jennie McKee is a senior science writer for AAOS Now. She can be reached at mckee@aaos.org

References:

• “Platelet-rich Plasma in Orthopaedic Applications: Evidence-based Recommendations for Treatment”
• Schwarz A: A Promising Treatment for Athletes, in Blood. New York Times, 2009 Feb 16.