Leucocyte-rich and platelet-rich fibrin for the treatment of bisphosphonate-related osteonecrosis of the jaw: a prospective feasibility study

Abstract

Our aim was to assess the feasibility of using leucocyte-rich and platelet-rich fibrin (L-PRF) for the treatment of bisphosphonate-related osteonecrosis of the jaw (BRONJ) in a single group study. After treatment with L-PRF, the response of each patient was recorded 1 month and 4 months postoperatively. Further assessments were made of the site, stage, concentration of c-terminal crosslinked telopepide of type 1 collagen, and actinomycosis. Among the total of 34 patients, 26 (77%) showed complete resolution, 6 (18%) had delayed resolution, and 2 (6%) showed no resolution. There was a significant association between the response to treatment and the stage of BRONJ (p = 0.002) but no other significant associations were detected. This study has shown that it is feasible to use L-PRF for the treatment of BRONJ, but the effectiveness cannot be judged with this study design. Randomised prospective trials are needed to confirm this.

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.