Can platelet-rich fibrin improve healing after surgical treatment of medication-related osteonecrosis of the jaw? A pilot study

doi:10.1016/j.oooo.2018.06.007

Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology

Volume 126, Issue 5, November 2018, Pages 390-403

https://doi.org/10.1016/j.oooo.2018.06.007 Get rights and content

Objective

The aim of this study was to evaluate the efficacy of platelet-rich fibrin (PRF) after bone surgery compared to surgery alone in the treatment of medication-related osteonecrosis of the jaw (MRONJ).

Study Design

A total of 47 patients with diagnosis of stage II or III of MRONJ were recruited at the Academic Hospital of Magna Graecia University of Catanzaro and allocated to 2 groups: In the first, patients were treated with PRF in addition to surgery (PRF group), in the other, only bone surgery was performed (non-PRF group). Fisher's exact and Student t tests were used to evaluate differences between the 2 surgical protocols in terms of mucosal integrity, absence of infection, and pain evaluation at scheduled follow-ups of 1 month (T1), 6 months (T2), and 1 year (T3).

Results

Analysis of mucosal integrity, absence of infection, and pain evaluation showed a significant difference between the 2 groups in favor of PRF only at T1 (P < .05), whereas no differences were determined at T2 and T3 (P > .05).

Conclusions

Our results suggested that local application of PRF after bone surgery may improve the quality of life limited to the short-term follow-up and reduce pain and postoperative infections.

Section snippets

Study sample

According to the Declaration of Helsinki on medical protocol and ethics, the regional Ethical Review Board of Central Calabria (reference for Magna Graecia University of Catanzaro, Catanzaro, Italy) approved the study. The study was designed as a prospective randomized, single-blind, monocentric clinical trial. The sample size was not calculated. Informed consent was obtained from all patients enrolled. Forty-seven patients who were diagnosed with MRONJ during the period November 2015 to

Patient characteristics

The study included 47 patients (24 women and 23 men). They were divided into 2 groups: (1) 24 patients (10 women and 14 men) treated with PRF in addition to traditional surgical removal of necrotic bone (PRF group); (2) 23 patients (14 women and 9 men) treated by following the traditional treatment protocol (non-PRF group). Detailed patient data are shown in Table I. The mean age of the patients was 74.7 ± 6.5 years (75.5 ± 5.6 years in the PRF group and 73.9 ± 7.4 years in the non-PRF group).

Discussion

The goal of treatment for patients developing MRONJ is to preserve quality of life, especially in those patients who have active disease. In particular, it is important to control pain, manage infection, and promote healing of surrounding bone. Although conservative treatment may resolve the patient's complaint, in cases where prolonged bone exposure shows no improvement, additional treatment is needed. Typically, these patients have stage II or III (AAOMS classification) disease, where the

Conclusions

Long-term evaluation showed no statistical differences between the PRF and non-PRF groups in terms of mucosal healing and absence of infection. Local application of PRF after bone surgery showed significant improvement in terms of quality of life in short-term follow-up and resulted in reduction in re-interventions necessary for healing.

Considering the limitations of the present study (a small study sample, monocentric study, and heterogeneous drug administrations), our results are not

References (55)

SL Ruggiero et al.
American Association of Oral and Maxillofacial Surgeons position paper on medication-related osteonecrosis of the jaw—2014 update
J Oral Maxillofac Surg
(2014)
SL Ruggiero et al.
American Association of Oral and Maxillofacial Surgeons position paper on bisphosphonate-related osteonecrosis of the jaws—2009 update
J Oral Maxillofac Surg
(2009)
R Fliefel et al.
Treatment strategies and outcomes of bisphosphonate-related osteonecrosis of the jaw (BRONJ) with characterization of patients: a systematic review
International J Oral Maxillofac Surg
(2015)
R Landesberg et al.
Inhibition of oral mucosal cell wound healing by bisphosphonates
J Oral Maxillofac Surg
(2008)
A Giudice et al.
Can autofluorescence guide surgeons in the treatment of medication-related osteonecrosis of the jaw? A prospective feasibility study
J Oral Maxillofac Surg
(2018)
MA Lerman et al.
Conservative management of bisphosphonate-related osteonecrosis of the jaws: staging and treatment outcomes
Oral Oncol
(2013)
F Moretti et al.
A prospective clinical trial for assessing the efficacy of a minimally invasive protocol in patients with bisphosphonate-associated osteonecrosis of the jaws
Oral Surg Oral Med Oral Pathol Oral Radiol Endod
(2011)
O Ristow et al.
Treatment perspectives for medication-related osteonecrosis of the jaw (MRONJ)
J Cranio-Maxillofac Surg
(2015)
M Del Fabbro et al.
Autologous platelet concentrates for bisphosphonate-related osteonecrosis of the jaw treatment and prevention. A systematic review of the literature
Eur J Cancer
(2015)
P Lopez-Jornet et al.
Medication-related osteonecrosis of the jaw: is autologous platelet concentrate application effective for prevention and treatment? A systematic review
J Cranio-Maxillofac Surg
(2016)

DM Dohan et al.

Platelet-rich fibrin (PRF): a second-generation platelet concentrate. Part II: Platelet-related biologic features

Oral Surg Oral Med Oral Pathol Oral Radiol Endod

(2006)

RE Marx et al.

Platelet-rich plasma: growth factor enhancement for bone grafts

Oral Surg Oral Med Oral Pathol Oral Radiol Endod

(1998)

MC Adornato et al.

The treatment of bisphosphonate-associated osteonecrosis of the jaws with bone resection and autologous platelet-derived growth factors

J Am Dent Assoc

(2007)

S Bocanegra-Pérez et al.

Use of platelet-rich plasma in the treatment of bisphosphonate-related osteonecrosis of the jaw

Int J Oral Maxillofac Surg

(2012)

M Mozzati et al.

Platelet-rich therapies in the treatment of intravenous bisphosphonate-related osteonecrosis of the jaw: a report of 32 cases

Oral Oncol

(2012)

J-W Kim et al.

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

Br J Oral Maxillofac Surg

(2014)

DM Dohan et al.

Platelet-rich fibrin (PRF): a second-generation platelet concentrate. Part I: Technological concepts and evolution

Oral Surg Oral Med Oral Pathol Oral Radiol Endod

(2006)

L Fortunato et al.

Management of facial pyoderma gangrenosum using platelet-rich fibrin: a technical report

J Oral Maxillofac Surg

(2018)

SCBCBS Soydan et al.

Management of bisphosphonate-related osteonecrosis of the jaw with a platelet-rich fibrin membrane: technical report

J Oral Maxillofac Surg

(2014)

F Hallmer et al.

Bacterial diversity in medication-related osteonecrosis of the jaw

Oral Surg Oral Med Oral Pathol Oral Radiol

(2017)

G Colapinto et al.

Patients osteometabolic control improves the management of medication-related osteonecrosis of the jaw

Oral Surg Oral Med Oral PatholOral Radiol

(2018)

ER Carlson et al.

The role of surgical resection in the management of bisphosphonate-related osteonecrosis of the jaws

J Oral Maxillofac Surg

(2009)

K Rupel et al.

A systematic review of therapeutic approaches in bisphosphonates-related osteonecrosis of the jaw (BRONJ)

Oral Oncol

(2014)

J Choukroun et al.

Platelet-rich fibrin (PRF): a second-generation platelet concentrate. Part IV: Clinical effects on tissue healing

Oral Surg Oral Med Oral Pathol Oral Radiol Endod

(2006)

CY Su et al.

In vitro release of growth factors from platelet-rich fibrin (PRF): a proposal to optimize the clinical applications of PRF

Oral Surg Oral Med Oral Pathol Oral Radiol Endod

(2009)

MAT Martins et al.

Association of laser phototherapy with PRP improves healing of bisphosphonate-related osteonecrosis of the jaws in cancer patients: a preliminary study

Oral Oncol

(2012)

MM Curi et al.

Bisphosphonate-related osteonecrosis of the jaws—an initial case series report of treatment combining partial bone resection and autologous platelet-rich plasma

J Oral Maxillofac Surg

(2011)

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Histopathological assessment of the preventive effect of leukocyte-platelet-rich fibrin on bisphosphonate-related osteonecrosis of the jaw following dental extraction: An animal study
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Leukocyte- and platelet-rich fibrin (L-PRF) could be considered a preventive measure in Bisphosphonate-Related Osteonecrosis of the Jaw (BRONJ). The present experiment aimed to assess the preventive effects of L-PRF on osteonecrosis of the jaw in rats.
In this interventional animal study with a split-mouth design, 28 rats were randomly allocated to saline (negative control), bisphosphonate (positive control), and Bis + L-PRF (case) groups. Bilateral extraction of maxillary molar teeth was performed followed by random application of L-PRF to one of the extraction sockets treated with Zoledronic acid for four weeks. Clinical occurrence of BRONJ and histopathologic evaluations were done, and data were subjected to the Kruskal-Wallis test, Mann-Whitney U test and exact Fisher test performed using SPSS 25. The significance level was set at 0.05.
The application of L-PRF resulted in a 41.67% reduction in osteonecrosis centers and the number of osteoclast cells. Also, Kruskal Wallis test results showed a significant difference among the three groups regarding the frequency distribution of inflammation severity. However, no significant difference was detected regarding the frequency distribution of the blood vessels (Kruskal Wallis test, P-value = 0.649).
It could be inferred that possible preventive effects on the clinical occurrence of osteonecrosis could be expected from the application of L-PRF.
A liquid chromatography-tandem mass spectrometry method for the quantification of ampicillin/sulbactam and clindamycin in jawbone, plasma, and platelet-rich fibrin: Application to patients with osteonecrosis of the jaw
2023, Journal of Pharmaceutical and Biomedical Analysis
Citation Excerpt :
A possible approach to counteract this is the use of various autologously produced platelet concentrates such as platelet-rich plasma (PRP) or platelet-rich fibrin (PRF). Especially the use of PRF has increased in recent years in the field of periodontology and oral and maxillofacial surgery [19,20] and is also executed at the Department of Oral and Maxillofacial Plastic Surgery in Würzburg. Both forms are obtained by centrifugation of patient blood, whereby PRF does not need additional anticoagulants for preparation.
Ampicillin in combination with sulbactam is a widely used drug choice for infection prophylaxis, especially in oral and maxillofacial surgery. Clindamycin serves as an alternative in patients with known allergy to β-lactam antibiotics. To ensure effective prophylaxis, it is important to achieve sufficiently high concentrations of active antibiotic substances in the tissues affected by the surgery. To this end, a LC-MS/MS method was developed and validated that allows the quantification of ampicillin, sulbactam and clindamycin in jawbone, plasma, and so-called platelet-rich fibrin (PRF). Validation was performed in accordance with the European Medicines Agency guidelines for bioanalytical method validation. For all matrices, sample processing was carried out by protein precipitation with acetonitrile or methanol 80%, containing the isotope labelled internal standards (IS) of the three drugs. Analytes were separated on a pentaflourophenyl column at 20 °C using gradient elution. Furthermore, detection was accomplished by electrospray ionisation in positive-ion mode (ampicillin, clindamycin and corresponding IS) and negative-ion mode (sulbactam and corresponding IS) in combination with multiple reaction monitoring. Depending on the analyte and the matrix under investigation, calibration curves ranged from 0.14 to 59.8 µg/g (jawbone - ampicillin), 2.0–1000 µg/mL (plasma - ampicillin), and 1.0–495 µg/mL (PRF - ampicillin). All analytes fulfilled the requirements of the guideline regarding sensitivity, linearity, selectivity, carryover, within-run and between run accuracy and precision, matrix effect and extraction recovery in all matrices. The method was successfully applied to measure concentrations of ampicillin, sulbactam and clindamycin in real-life samples obtained in routine clinical practice.
Combined approach to treatment of advanced stages of medication-related osteonecrosis of the jaw patients
2022, Brazilian Journal of Otorhinolaryngology
Citation Excerpt :
Surgically, it helps homeostasis and prevents flap opening, promoting the remodeling and recovery of both soft and hard tissues. In a single randomized clinical trial examining the effectiveness of PRF in MRONJ treatment, Giudice et al.26 treated 47 Stage 2–3 patients in a study in which they evaluated the efficacy of PRF in MRONJ treatment. 24-patients underwent PRF treatment in addition to surgery and 23-patients underwent only surgery without PRF.
Increased incidence of localized osteonecrosis in the jaw bones caused by bisphosphanate use and reduced quality of life of the patients led researchers to diagnose the disease in the early period and to investigate the effective treatment modality.
Treatment of medication-related osteonecrosis of the jaw patients is based on individual protocols from clinical experience, as there are no definitive treatment guidelines. In view of the lack of consensus on the effectiveness of medication-related osteonecrosis of the jaw treatments in the literature, the aim of this study was to evaluate the surgical technique described in the treatment of advanced stages of medication-related osteonecrosis of the jaw patients.
Twenty-one patients affected by Stage 2–3 medication-related osteonecrosis of the jaw were treated with ultrasonic piezoelectric bone surgery for necrotic bone removing, leukocyte and platelet-rich fibrin concentrate obtained from the patient’s peripheral blood and Nd:YAG laser for biostimulation. Success was assessed as the maintenance of full mucosal coverage without signs of residual infection at 1-month (T1), 3-months (T2), 6-months (T3) and 1-year (T4) after surgery. Logistic regressions were used to evaluate the association between the different independent variables and treatment outcomes.
Two Stage 3 patients had delayed healing at 1 month after the operation. Complete mucosal healing was achieved in all patients at the third month. Multivariate analysis demonstrated that different variables were not significantly correlated with delayed healing (p > 0.05).
The surgical protocol presented in this study shows promising results for surgical management of advanced stages of medication-related osteonecrosis of the jaw patients.
Platelet-rich fibrin as a treatment option for osteoradionecrosis: A literature review
2022, Journal of Stomatology, Oral and Maxillofacial Surgery
The aim of this review is to establish the usefulness and effectiveness of using platelet-rich fibrin (PRF) in the treatment of osteoradionecrosis (ORN) lesions. A review of the literature was performed using keywords through the PubMed-Medline and Cochrane Library search engine. Inclusion criteria were: (1) original publication in either the French or the English language, (2) studies conducted in humans, (3) presence of ORN lesions following head and neck radiotherapy (RT), (4) use of PRF or derivates in the treatment of ORN lesions, (5) clinical variables and outcomes mentioned in the study. Overall, four case reports were retained. Two publications were removed from the initial seven results after application of the inclusion criteria. A recent randomised clinical trial was not considered since the group analysed the effectiveness of leukocyte-enriched Plasmas-Rich-Fibrin (LPRF) in preventing ORN, but not in treating it. Therefore, four publications were retained for analysis. Results suggest that using PRF as an adjunct to surgical therapy is beneficial in treating ORN lesions although no controlled studies were found. Therefore, additional controlled clinical studies are warranted to better define the effectiveness and recommendation of this approach.
Efficacy of complementary treatment with autologous platelet concentrates and/or mesenchymal stem cells in chemical osteonecrosis of the jaw. Systematic review of the literature
2022, Journal of Stomatology, Oral and Maxillofacial Surgery
The aim of this systematic review was to establish the current status of the subject and find out what scientific evidence we have on the use of autologous plasma concentrates (APCs) and mesenchymal stem cells (MSCs) as complementary therapies at the management of Medication-related Osteonecrosis of the jaw (MRONJ). We performed a literature search of articles published between December 2019 to January 2020 in electronic databases, in accordance to PRISMA system. The variables analyzed were: the number of patients, age, sex, medical history, origin of MRONJ, imaging studies, treatment performed, and evolution of MRONJ. The articles included in the review were grouped into two groups (Group A “Therapy with APCs” and Group B “Therapy with APCs and MSCs”). Newcastle-Ottawa scale (NOS) was used to assess the quality of the articles. Fisher's exact test was used to evaluate eventual differences between groups. Of the 306 patients who were included, 297 belonged to Group A and 9 to Group B. In our sample, women predominated against men and no significant differences in age were observed. Osteoporosis was the most frequent underlying disease in both groups. The most common origin of MRONJ was oral surgery in group A. Conservative surgery was performed in all patients, but complementary treatment was applied in different ways in each group. The resolution of the pathology was achieved in 90% of cases in both groups without significant differences between them. The mean score of the reviewed studies at NOS was 4. There are currently no published scientific data that can sufficiently support the use of APCs and MSCs for the treatment of established MRONJs.
Surgical vs conservative treatment of medication-related osteonecrosis of the jaw: A complex systematic review and meta-analysis
2021, Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology
The objective of this study was to compare the outcome of surgical and conservative treatment approaches for medication-related osteonecrosis of the jaw.
Publications in Medline, The Cochrane Library, EMBASE, and PubMed (non-indexed articles) and by Health Technology Assessment organizations were searched. Quality of evidence in primary studies were assessed using Grading of Recommendations Assessment, Development and Evaluation (GRADE) and the level of bias in systematic reviews by a measurement tool to assess systematic reviews (AMSTAR).
Quality assessment identified 3 primary studies with moderate GRADE score. Moderate risk of bias was found in 7 systematic reviews and low risk of bias in 3. Nine studies were included in the meta-analysis, where 62.1% healing was reported after surgical treatment (144 of 232 included patients) and 28.8% healing was reported after conservative treatment (38 of 132 included patients). Moderate heterogeneity was found among the included studies (P = .02). The overall odds ratio for resolution of osteonecrosis after surgical versus conservative treatment was 1.25 (95% confidence interval, 0.24-2.26) and was not statistically significant.
Slightly better outcomes are reported after surgical treatment, in particular for advanced disease stages, but there is a lack of standardized treatment protocols and outcome measures. Overall, the quality of evidence is poor, and the majority of studies have a low evidence certainty rating and high risk of bias.

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Oral and Maxillofacial SurgeryCan platelet-rich fibrin improve healing after surgical treatment of medication-related osteonecrosis of the jaw? A pilot study

Objective

Study Design

Results

Conclusions

Section snippets

Study sample

Patient characteristics

Discussion

Conclusions

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Can platelet-rich fibrin improve healing after surgical treatment of medication-related osteonecrosis of the jaw? A pilot study