Leucocyte-rich and platelet-rich fibrin for the treatment of bisphosphonate-related osteonecrosis of the jaw: a prospective feasibility study
Introduction
Since the first report of bisphosphonate-related osteonecrosis of the jaw (BRONJ) in 2003,1 it has been recognised as a serious complication of the drug. BRONJ is defined as an area of exposed bone in the maxillofacial region that has not healed within 8 weeks of identification in a patient who was taking or had been exposed to bisphosphonates and had not had radiotherapy to the craniofacial region.2 Though there have been many efforts to establish the pathophysiology of the disease,3, 4, 5, 6 it is poorly understood. Currently, it is known to be associated with oversuppression of bone remodelling,3, 4 antiangiogenic effects,5 and soft tissue toxicity6 on the basis of the pharmacological effects of bisphosphonates.
Many sources, including the American Association of Oral and Maxillofacial Surgeons7 (AAOMS) and the American Society for Bone and Mineral Research2 (ASBMR) have recommended conservative approaches, including systemic treatment with antibiotics, oral antimicrobial rinses, and minimal debridement. However, these treatments have yielded controversial results and are not always effective. New approaches, including recombinant human parathyroid hormone,8 laser phototherapy,9 and platelet concentrates10, 11 have therefore been suggested.
Platelet concentrates are autologous products that contain high concentrations of several protein growth factors such as platelet-derived growth factor, transforming growth factor β,vascular endothelial growth factor (VEGF), and endothelial growth factor, all of which are secreted by platelets.12 This platelet-enriched preparation is reported to stimulate and accelerate healing of tissue and bony regeneration, and is being used as an effective adjunct in many fields.13, 14 Recently, several reports have shown promising results from the use of platelet-rich plasma for BRONJ,10, 11, 15 and this has become a popular use for platelet concentrates.
However, a new method that incorporates the use of platelet concentrates is leucocyte-rich and platelet-rich fibrin (L-PRF). It is characterised by no addition of chemicals, which allows the natural coagulation processs,16 and it has characteristics that differ from those of PRP. Unlike PRP it does not dissolve quickly after use, which leads to an increased lifespan for cytokines and shows a substantial embedding of the growth factors of platelets and leucocytes into the more favourable architecture of the physiological fibrin matrix.17 The roles of leucocytes in platelet concentrates such as anti-infectious action, immune regulation,18 and a capacity to produce large amounts of VEGF,19 have attracted attention. Although L-PRF has different biological characteristics and is more usable than PRP, we know of few studies regarding its use in BRONJ. The aim of this pilot study was, therefore, to assess the feasibility of the use of L-PRF in the treatment of BRONJ.
Section snippets
Study design and data collection
We designed and implemented a single group study involving patients who visited the Department of Oral and Maxillofacial Surgery at the Ewha Womans University Medical Center in Seoul, Korea, between January 2006 and December 2012. The inclusion criteria were: patients who were, or who had had, treatment with bisphosphonates, and were diagnosed with BRONJ according to the definition provided by the ASBMR task force,2 or patients with sites that had failed to heal for 8 weeks or longer despite
Results
From January 2006 to December 2012, a total of 34 women (mean (SD)age 71 (13) years) were included; their baseline characteristics are shown in Table 1, and their response to treatment in Table 2.
After treatment with L-PRF, 26 patients (77%) showed complete resolution, 6 (18%) had delayed resolution, and 2 (6%) did not resolve at all. Both of these 2 were being treated with zoledronate (for 24 and 63 months each) and both had had chemotherapy. Their lesions were similar even after intervention
Discussion
We aimed to assess the feasibility of giving L-PRF for the treatment of BRONJ. Given that no universally accepted treatment is currently available, the study was important in that it is the first to our knowledge that shows promising results after the application of L-PRF in a relatively large group of patients with BRONJ treated at a single hospital.
Platelet concentrate refers to an autologous concentration of human platelets that is obtained by centrifuging blood, and it produces a high
Conflict of Interest
We have no conflicts of interest.
Ethics statement/confirmation of patients’ permission
We followed the guidelines of the World Medical Association Declaration of Helsinki 2000 for biomedical research involving human subjects. The study was approved by the institutional review board of the University Medical Centre, and all participants provided written informed consent.
Acknowledgments
This study was supported by the Ewha Global Top5 Grant 2013 of the Ewha Womans University, Seoul, Korea. The authors declare no potential conflicts of interest with respect to the authorship and/or publication of this article.
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