Efficacy of platelet-rich plasma as conservative treatment in orthopaedics

Platelet rich plasma therapy (PRP) involves removing autologous blood and enriching the platelet content prior to injection at sites of injury. Clinicians in Italy introduced PRP in 1987 for autologous transfusion for cardiac surgery patients¹. Later, orthopaedic surgeons adapted PRP to promote adherence of bone graft material and to prevent tissue drying². Clinicians developed PRP as a treatment for musculoskeletal pain because platelets are a rich source of growth factors that may be beneficial for healing³. Companies quickly produced a multitude of commercial devices to generate PRP once clinicians began administering it to treat pain. These companies took advantage of an opportunity in the regulatory process to demonstrate equivalence to the previously approved devices. This resulted in US Food and Drug Administration (FDA) clearance for devices clinicians use to facilitate the off-label use of PRP. Although approved for use with bone grafting material, PRP is not approved for treating musculoskeletal pain. Despite being an off-label use, PRP for musculoskeletal pain is expected to grow into a global market and is projected to be worth as much as $ 4.5 billion (€ 3.88 billion) in the next decade². In the US, patients bear the full cost of PRP because most insurance companies will not reimburse the cost of experimental procedures that are not approved by the FDA, while in Europe, the cost of the treatment is borne by the national health systems. Physicians rapidly adopted PRP into their practice in spite of the lack of firm evidence to support its use, and its use by elite athletes⁴ (e.g. Tiger Woods⁵) represents an implicit advertising campaign, spurring demand.

In this issue of Blood Transfusion, Dr. Franchini and colleagues assess the available evidence for PRP use in orthopaedics⁶. The Authors include 36 randomised controlled trials of PRP involving 2073 patients. The studies were heterogeneous in their comparator group, therapeutic site, and PRP technique. All of the studies were under-powered, with a significant risk for bias, but overall they demonstrate that PRP is not associated with serious adverse events and may provide a modest improvement in pain scores for specific musculoskeletal conditions. Thus it would appear that PRP is a marginally effective but safe procedure that is widely available, despite limited evidence to support its use. Yet 93% of team physicians for elite athletes in the US routinely employ PRP⁴. And here lies a paradox that warrants further study.

The efficacy of PRP depends on the PRP source, preparation technique, administration and the recipient^3,7. Younger healthier patients heal faster than older patients who are not in good clinical condition, and young patients likely have a greater regenerative capacity to produce platelets⁸. Elite athletes are also more physically active, and this increases blood flow and places more strain on the injured tissue. Improved function and decreased pain would be more clinically apparent in athletes who push their bodies to extremes compared to the patients studied in the clinical trials. Team physicians for professional athletes also have significant resources that may influence PRP efficacy given the exorbitant investment in athletic performance and the impetus to protect trade secrets in order to gain a competitive edge over rival teams and players. Establishing PRP as an effective and reproducible treatment for musculoskeletal conditions will require an understanding of the mechanism of PRP-induced healing and patient factors that promote or impede its efficacy.

Further research has the potential to narrow the gap between outcomes in average patients and elite athletes after PRP. The first step is, indeed, to achieve a mechanistic understanding of PRP-induced healing. Platelet concentration is the defining feature of the injectate used for PRP, and understanding the relevant platelet biology will be key for improving this type of therapy. Platelets are not passive carriers of growth factors, as was presumed in the original rationale for PRP use, but they actively initiate healing through a selective release of proteins and chemokines in response to the wound microenvironment⁹. Current PRP preparations homogenise platelets to extract growth factors, which prevents platelets from responding to their environment. Subpopulations of platelets within the same individual respond differently to activation and likely vary in their regenerative capacity¹⁰. Enriching PRP for the most effective platelets could increase its therapeutic potential. Parabiotic experiments demonstrate that systemic factors present in blood transmit limited the beneficial properties of youth or detrimental effects of ageing¹¹. Therefore, PRP generated from younger donors may result in greater clinical efficacy at the expense of the increased risk of allogenic transfusion compared to autologous PRP. Understanding the mechanism of PRP-induced recovery will lead to novel ways to maximise its potential benefit to patients.

In summary, Dr. Franchini and colleagues have provided compelling evidence that PRP in its current form is safe and may be potentially beneficial for some, but conclude that further research is necessary to provide an effective, tailored and reproducible PRP treatment for the individual patient. This will require understanding the interaction between patients, the PRP source, the preparation method, and the injury involved in order to provide a therapy whose efficacy justifies the high cost of off-label treatment.