Autologous blood products in musculoskeletal medicineBMJ 2013; 346 doi: https://doi.org/10.1136/bmj.f2979 (Published 10 May 2013) Cite this as: BMJ 2013;346:f2979
- Nicola Maffulli, professor of musculoskeletal disorders, consultant orthopaedic surgeon
- 1Department of Musculoskeletal Disorders, Faculty of Medicine and Surgery, University of Salerno, 84081 Baronissi, Salerno, Italy
Participation in almost all sports and physical activities benefits individuals and society as a whole because it promotes health and helps prevent conditions such as osteoporosis, cardiovascular disease, and diabetes; it may also lead to improved mental health. Nevertheless, athletes are highly vulnerable to musculoskeletal injuries, sometimes with devastating effects. Sports injuries cost society billions of dollars in direct and indirect costs. Regenerative medicine technologies, such as autologous blood products for the treatment of tendinopathies, hold the promise of improved outcomes for musculoskeletal conditions that currently have limited or no treatment options. In a linked trial (doi:10.1136/bmj.f2310), Bell and colleagues compare the effectiveness of peritendinous injections of autologous blood with standard eccentric exercise in athletes with Achilles tendinopathy.1
Novel treatments that are reported to accelerate recovery from musculoskeletal injuries, without adversely affecting recurrence rate, are increasingly advocated in the lay media and often heavily promoted to athletes and healthcare professionals.2 3 Injections of autologous blood products, including whole blood, platelet rich plasma, and autologous conditioned serum, are increasingly used in the management of sport injuries, yet they are supported by a poor evidence base.4 Why are blood products appealing? Blood contains biologically active components responsible for haemostasis and can potentially initiate synthesis of new connective tissue and promote revascularisation.5 Growth factors present in blood products, and the potential of these growth factors to induce further release of such factors, is thought to improve the healing process in chronic injuries and to accelerate repair in acute and chronic lesions. Treatment with platelet rich plasma, in particular, is increasingly thought to accelerate muscle and tendon healing and to allow early return to competition in elite athletes. It is therefore often recommended as best practice for management of musculoskeletal injuries. The global market for this product, valued at $4.5m (£2.9m; €3.4m) in 2009, is expected to be worth more than $120m by 2016.6
Although autologous blood injections are routinely performed, many unanswered questions remain, including the most appropriate volume and frequency of injection, the ideal time between injections, and the mechanism by which the beneficial effect is harnessed.7 8 These treatments for musculoskeletal injuries have been tested in few well conducted randomised controlled clinical trials, and their optimal application is unclear. A recent systematic review showed that, when these products have been tested in appropriately powered studies, with strict outcome measures, by researchers with no conflicts of interest, the results have been underwhelming and would not justify the use of such products over more traditional treatment.9 Nevertheless, many experts swear by such treatments, and many athletes, coaches, managers, and agents would not forego these interventions after musculoskeletal injury.
Bell and colleagues’ study adds to the small evidence base in this field.1 Achilles tendinopathy is prevalent and debilitating, being common in athletes and the sedentary population. Indeed, it is often used as an example of troublesome chronic and recurrent soft tissue injury. The authors compared injection of whole blood with staple conservative management—eccentric exercises (although it is unclear whether these exercises are effective) and used appropriate outcome measures in an adequately powered study. Advocates of blood product treatments are likely to criticise the study on several grounds. Patients were enrolled after experiencing only three months of symptoms. However, it may be argued that from a biological viewpoint, the typical tendinopathic lesion, which represents a failed healing response, is already chronic at clinical presentation.10 The injections were unguided because the authors wished to reproduce the clinical situation of a clinician with no access to ultrasound guidance. Only two injections were performed, whereas many advocate at least three, although it is unclear whether three injections are better than two.
Other critics may say that it is not surprising that whole blood is ineffective and that platelet rich plasma should have been used. However, the only randomised controlled trial on the use of platelet rich plasma in Achilles tendinopathy found it to be no more effective than standard treatment.11 Furthermore, the results of a recent randomised trial that directly compared injections of platelet rich plasma and autologous whole blood indicated that whole blood was slightly superior at six months in patients with refractory elbow tendinopathy.12 It may be that not all tendons are the same and that, for example, the elbow extensor tendons are more amenable to blood product injections than tendons in other locations.13 However, even in the upper limb it is becoming apparent that autologous blood products, when tested in randomised controlled trials, are no more effective than standard, less expensive, and less time consuming care.14
Clinicians and patients often want a magic bullet, and autologous blood products seem to satisfy many requirements of different parties. They are easy to obtain and prepare, they seem to be safe and ethically and socially acceptable, they are not doping, they are hyped by the media, and they allow large profit margins. But do they actually work? Despite the findings of well conducted studies that suggest that they probably do not, it seems likely that they will continue to be widely used.
Cite this as: BMJ 2013;346:f2979
Competing interests: I have read and understood the BMJ Group policy on declaration of interests and declare the following interests: editor in chief, Muscles, Tendons and Ligaments Journal (www.mltj.org) and co-editor, Journal of Orthopaedic Surgery and Research
Provenance and peer review: Commissioned; not externally peer reviewed.