PRP shows promise, well-designed studies needed before conclusions can be made

The search for a minimally invasive solution to improve tissue repair is highly desirable. The use of platelet-rich plasma is a simple and minimally invasive way to obtain a natural concentration of autologous growth factors and apply them to a lesion site to improve healing in tissues with low healing potential.

With several fields of application, the rationale for using platelets for the treatment of different tissues is their reservoir of critical growth factors and cytokines which may govern and regulate the healing process, which is quite similar for all kinds of tissues.

Despite interesting and promising pre-clinical findings, the number of published clinical studies regarding platelet-rich plasma (PRP) application is limited, with the majority of published studies involving applications on tendons.

Intratendinous injections

In our study published in Injury in 2009, we described our preliminary results with multiple PRP injections for the treatment of patellar tendinopathy. We found this treatment to be safe and promising. We also underlined the need for concomitant rehabilitative treatment — the application of synergic biological and mechanical stimulation and reduction of the extensor apparatus overload — thus aiding healing of the tendon and maintaining the results over time. Further analysis confirmed the contribution of PRP to the healing process.

In another study published in International Orthopaedics in 2010, we included 15 patients affected by chronic jumper’s knee who had failed previous nonsurgical or surgical treatments, whom we treated with multiple PRP injections and physiotherapy. Most of the patients improved markedly and returned to previous activities.

We have also used multiple PRP injections for the treatment of acute partial rupture of the Achilles tendon in an athlete: the fast tissue repair, documented by MRI and ultrasound imaging, allowed a swift return to full functionality and competitive sports activity. Our results were published in Orthopedics in 2010.

Contrasting findings

Contrasting findings have been shown in cases of chronic Achilles tendinopathy. De Vos and colleagues performed a randomized trial comparing 27 patients treated with a single PRP injection to a homogeneous group of patients treated with saline injections. They found no difference in pain and activity improvement at 6-month follow-up, according to their article in a 2010 issue of the Journal of the American Medical Association. However, due to the method used and patients selected, these conclusions are difficult to extend to the numerous clinical applications of PRP.

Knee degenerative conditions

Another common application of PRP is for the treatment of knee degenerative conditions. We conducted a pilot study that included 100 patients treated with intra-articular PRP injections. Our study provided evidence of the technique’s safety and showed pain reduction and improved function. Only minor adverse events were detected, such as a mild pain reaction and effusion after the injections, which persisted for no more than 2 days. A significant improvement was observed in all of the parameters evaluated, although we observed a tendency of worsening at 1-year evaluation, according to our results published in a 2010 issue of Knee Surgery, Sports Traumatology, Arthroscopy.

We performed a subsequent evaluation at 2-year follow-up and confirmed the same trend toward an overall worsening of the results. We determined the median duration of the beneficial effect to be 9 months. However, a high range of effect persistency was observed. In fact, higher and longer effects were documented in young men with a low body mass index and a low degree of cartilage degeneration, whereas other patients presented less durable results. These results are included in a study of ours’ that has been accepted for publication in Knee Surgery, Sports Traumatology, Arthroscopy.

Other possible fields of application include ACL or meniscal repair augmentations and treatment of muscle lesions, but research in these fields is still at an early stage, with only preliminary and contradictory results.

Using a patient’s own growth factors

The attractive possibility of using patients’ own growth factors to enhance reparative processes in tissues with low healing potential, the promising preliminary clinical findings and the safety of these methods explain the wide use of this biological approach. However, despite these premises and the wide use of these products, research into their clinical efficiency is still in its infancy. Only a few studies report preliminary results, and the design of these studies is not optimal.

Some interesting findings have been obtained — especially in pre-clinical studies — but in most cases results are still preliminary and controversial. The controversies and difficulty in this field of research are increased by the numerous products used, which makes it difficult to compare results across studies. The various preparation methods and the different platelet concentrations obtained, as well as other variables, such as activation modalities and the presence of white blood cells within the platelet concentrate, are confounding factors when comparing the results of different studies. This is true for both pre-clinical studies and for evaluating the effectiveness of this approach in humans for the treatment of musculoskeletal injuries.

Platelet rich plasma is an innovative approach that matches many of the criteria of an ideal treatment, but randomized, well-designed studies are still needed to clarify its real potential and improve preparation methods and application modalities. Until more robust evidence is available to support its use for the treatment of musculoskeletal injuries, the clinical applications of platelet-derived growth factors should be limited to well-controlled trials.

Elizaveta Kon, MD, Giuseppe Filardo, MD, and Maurilio Marcacci, MD, can be reached at the Biomechanics Laboratory – III Clinic, Rizzoli Orthopaedic Institute, Via Di Barbiano 1/10 – 40136 Bologna, Italy; +39-051-6366567; e-mail: e.kon@biomec.ior.it, g.filardo@biomec.ior.it, or m.marcacci@biomec.ior.it.

References:

• De Vos RJ, Weir A, van Schie HT, et al. Platelet-rich plasma injection for chronic Achilles tendinopathy: a randomized controlled trial. JAMA. 2010;303(2):144-149.
• Filardo G, Kon E, Della Villa S, et al. Use of platelet-rich plasma for the treatment of refractory jumper’s knee. Int Orthop. 2009;34(6):909-915.
• Filardo G, Presti ML, Kon E, Marcacci M. Nonoperative biological treatment approach for partial Achilles tendon lesion. Orthopedics. 2010;33(2):120-123.
• Filardo G, Kon E, Buda R, et al. Platelet-rich plasma intra-articular knee injections for the treatment of degenerative cartilage lesions and osteoarthritis. Knee Surg Sports Traumatol Arthrosc. Accepted for publication.
• Kon E, Buda R, Filardo G, et al. Platelet-rich plasma: intra-articular knee injections produced favorable results on degenerative cartilage lesions. Knee Surg Sports Traumatol Arthrosc. 2010;18(4):472-479.
• Kon E, Filardo G, Delcogliano M, et al. Platelet-rich plasma: new clinical application: a pilot study for treatment of jumper’s knee. Injury. 2009;40(6):598-603.