Surgical management of bisphosphonate induced osteonecrosis of the jaws

doi:10.1016/j.ijom.2009.11.014

International Journal of Oral and Maxillofacial Surgery

Volume 39, Issue 3, March 2010, Pages 251-255

https://doi.org/10.1016/j.ijom.2009.11.014 Get rights and content

Abstract

Recent literature contains numerous articles on osteonecrosis of the jaws (ONJ) associated with bisphosphonate treatment (BPT), with most advocating a conservative approach to management. A prospective study was designed to review the surgical management of cases of ONJ that did not respond to conservative management. Forty patients, referred with ONJ that did not respond to conservative management, were treated surgically and followed up for 6 months to 4 years. Four patients were taking i.v. BPT as part of their bone cancer management and 16 were taking oral BPT for osteoporosis. The surgical management of ONJ involved antibiotic therapy, surgical debridement of all necrotic bone and tension-free primary closure. All 40 cases healed uneventfully with no wound breakdown during follow-up. Most of the literature supports the conservative management of ONJ, but the condition leaves the patient debilitated. Many cases do not respond to conservative management and the infection and bone destruction is progressive. The conservative management of ONJ is to be supported, but this prospective study has shown that those cases that do not respond may be managed surgically. It should be recognized that while the results of this paper are encouraging, some cases will be resistant to all treatments.

Section snippets

Methods

Forty patients, who were referred with ONJ that did not respond to conservative management, were treated surgically and followed up for periods of 6 months to 4 years. The surgical management of the ONJ involved antibiotic therapy, surgical debridement of all necrotic bone and primary closure without tension. Prior to being considered for surgical debridement, all patients with ONJ were managed conservatively for a minimum of 3 months. Conservative management followed the guidelines outlined by

Results

This prospective study involved 40 patients, who were referred with ONJ that did not respond to conservative management, and were treated surgically and followed up for periods of 6 months to 4 years (mean 20 months). There were 25 females and 15 males in the study. Twenty-four patients were taking intravenous bisphosphonate as part of their bone cancer management. Eleven patients had breast cancer metastases, eight had prostate metastases, four had multiple myeloma and one patient had Paget's

Discussion

Most of the literature supports the conservative management of ONJ with only minor surgical debridement being undertaken in the more recalcitrant case. This condition leaves the patient quite debilitated, especially those who are being treated for cancer. Many cases do not respond to conservative management and the infection and bone destruction are progressive. Therefore it is important to develop a surgical protocol that can deal with this condition. This prospective study reviewed 40

Competing interests

None declared.

Funding

None.

Ethical approval

No ethical approval was needed for this study. Those patients that elected to undergo surgical debridement were counselled as to the nature of this prospective study and signed consent forms to this effect.

References (14)

R.E. Marx
Pamidronate (Aredia) and Zoledronate (Zometa) induced avascular necrosis of the jaws: a growing epidemic
J Oral Maxillofac Surg
(2003)
M.A. Pogrel
Bisphosphonates and bone necrosis
J Oral Maxillofac Surg
(2004)
S.L. Ruggiero et al.
Osteonecrosis of the jaws associated with the use of bisphosphonates: a review of 63 cases
J Oral Maxillofac Surg
(2004)
J. Wang et al.
Osteonecrosis of the jaws associated with cancer chemotherapy
J Oral Maxillofac Surg
(2003)
N.B. Watts
Bisphosphonate treatment of osteoporosis
Clin Geriatr Med
(2003)
Expert panel recommendations: dental management of patients receiving oral bisphosphonate therapy
J Am Dental Assoc
(2006)
A. Badros et al.
Osteonecrosis of the jaw in multiple myeloma patients: clinical features and risk factors
J Clin Oncol
(2006)

There are more references available in the full text version of this article.

Cited by (101)

Factors affecting the quality of life of patients with medication-related osteonecrosis of the jaw during treatment: A quality-of-life survey and causal analysis
2024, Journal of Cranio-Maxillofacial Surgery
This prospective cohort study aimed to investigate the impact of medication-related osteonecrosis of the jaw (MRONJ) on health-related quality of life (HRQOL) and oral health-related QOL (OHRQOL) and the association between the downstaging of MRONJ and OHRQOL.
The HRQOL and OHRQOL of 44 patients with MRONJ were assessed using the SF-36v2 and the General Oral Health Assessment Index (GOHAI), respectively. Treatment was performed in accordance with the AAOMS position paper (2014). The SF-36v2 and GOHAI scores at the beginning of the survey were used to evaluate the impact of MRONJ on QOL. Potential confounders affecting the association between downstaging and QOL improvement were selected using directed acyclic graphs. Multiple regression analysis was performed to evaluate causal inferences.
HRQOL scale scores declined below the national average. The three-component summary score (3CS), comprising the physical component summary (PCS), mental component summary (MCS), and role/social component summary (RCS), revealed that performance status and primary disease significantly affected the PCS and RCS (P = 0.005 and P < 0.001, respectively) and PCS and MCS (P = 0.024 and P = 0.003, respectively). The MRONJ stage did not influence the 3CS; however, OHRQOL declined in a stage-dependent manner (P = 0.005). Downstaging of MRONJ was independently associated with the improvement rate of the total GOHAI scores after adjusting for variables (P = 0.045).
The HRQOL of patients with MRONJ declined; however, this may depend on the underlying disease status rather than the MRONJ stage. Improvement of the disease status can potentially predict an improvement in OHRQOL, regardless of the treatment modality.
American Association of Oral and Maxillofacial Surgeons’ Position Paper on Medication-Related Osteonecrosis of the Jaws—2022 Update
2022, Journal of Oral and Maxillofacial Surgery
Strategies for management of patients with, or at risk for, medication-related osteonecrosis of the jaws (MRONJ) – formerly referred to as bisphosphonate-related osteonecrosis of the jaws (BRONJ)—were set forth in the American Association of Oral and Maxillofacial Surgeons (AAOMS) position papers in 2007, 2009 and 2014. The position papers were developed by a committee appointed by the AAOMS Board of Trustees and comprising clinicians with extensive experience in caring for these patients, as well as clinical and basic science researchers. The knowledge base and experience in addressing MRONJ continues to evolve and expand, necessitating modifications and refinements to the previous position papers. Three members of the AAOMS Committee on Oral, Head, and Neck Oncologic and Reconstructive Surgery (COHNORS) and three authors of the 2014 position paper were appointed to serve as a working group to analyze the current literature and revise the guidance as indicated to reflect current knowledge in this field. This update contains revisions to diagnosis and management strategies and highlights the current research status. AAOMS maintains that it is vitally important for this information to be disseminated to other relevant healthcare professionals and organizations.
Incidence of and risk factors for medication-related osteonecrosis of the jaw in women with breast cancer with bone metastasis: a population-based study
2020, Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology
The aim of this study was to prospectively determine the incidence of medication-related osteonecrosis of the jaw (MRONJ) and define risk factors in patients with metastatic breast cancer treated with zoledronic acid and/or denosumab.
In a prospective cohort study performed in Region Skåne, Sweden, from January 1, 2012, until December 31, 2015, all patients with breast cancer who had radiographic evidence of bone metastases and were treated with zoledronic acid or denosumab were included and followed up until May 31, 2018.
Of the 242 patients, MRONJ developed in 16 (6.6%) during the 77 months of study. The incidence of MRONJ in patients treated with zoledronic acid was 4.1%, and in patients treated with denosumab, it was 13.6%. The risk of MRONJ was higher in patients on denosumab than in those treated with zoledronic acid (P = .011). Corticosteroid use was associated with a decreased risk of MRONJ (P = .008), and diabetes was associated with an increased risk of MRONJ (P = .02).
The incidence of MRONJ is 13.6% (>3 times higher) in denosumab-treated patients with breast cancer compared with that in patients treated with zoledronic acid (4.1%). Corticosteroid use decreased the risk of MRONJ.
Antimicrobial photodynamic and photobiomodulation adjuvant therapies for prevention and treatment of medication-related osteonecrosis of the jaws: Case series and long-term follow-up
2020, Photodiagnosis and Photodynamic Therapy
Medication-Related Osteonecrosis of the Jaws (MRONJ) incidence are increasing among elderly. Treatment can be challenging. Prevent or treatment protocols that control evolution of the lesion are warranted.
To observe long-term outcomes of two protocols based on photonics [antimicrobial photodynamic therapy (aPDT) and photobiomodulation (PBM)] for prevention and treatment of MRONJ lesions.
In a prospective study, patients who needed oral surgery and had been exposed to antiresorptive drugs were long-term followed-up. For MRONJ prevention, immediately after tooth extraction aPDT was applied. For aPDT a 0.01 % methylene blue solution was applied inside socket for 5 min followed by irradiation with a diode laser [660 nm, 0.028cm², 0.1 W, 3.57 W/cm², 90 s and 9 J per point, 321 J/cm², at least at in 3 points (laser probe was placed at central, and two equidistant points) and total energy of 27J]. Irradiation was repeated weekly until total tissue repair. MRONJ treatment included preoperative aPDT sessions until signs and symptoms of infection had reduced. Then, after necrotic bone removal, aPDT was applied inside surgical wounds and re-applied weekly until healing. Antibiotics were administered pre or postoperatively for no longer than 7 days. PBM therapy was applied with 808 nm diode laser, 0.028cm², 0.1 W, 3.57 W/cm², 30 s, 107 J/cm², 3 J and total energy of 12 J until evidence of remission.
Eighteen patients underwent preventive protocol, and none presented signs of MRONJ after a follow-up of at least 6 months. Seventeen patients presented with MRONJ underwent aPDT protocol and sixteen of them showed total regression of lesions.
aPDT and PBM therapy protocols appear to be effective as adjuvant approach not only for preventing MRONJ development due to tooth extraction but for treating MRONJ lesions at early stages with no adverse effects.
Evaluation of the Efficacy of EDTA Chelation on Alveolar Bone Healing After Ultrasonic and Conventional Surgery Under Bisphosphonate Medication: A Rat Model
2019, Journal of Oral and Maxillofacial Surgery
The aims of the present study were 1) to investigate the effects of local ethylenediaminetetraacetic acid (EDTA) chelation on alveolar bone healing after systemic administration of bisphosphonates; and 2) to compare the healing in alveolar defects created with ultrasonic and conventional surgery.
A total of 40 male Wistar rats were divided into 4 equal groups of 10 rats each (zoledronate and piezosurgery, zoledronate and bur, placebo and piezosurgery, and placebo and bur). The first 2 groups received weekly intraperitoneal injections of zoledronic acid (0.06 mg/kg), and the second 2 groups received saline solution for 4 weeks. After the last injections, horizontal defects 4 × 2 × 1 mm in size were created on the mandibular alveolar bone using piezosurgery or conventional bur surgery. The zoledronate groups received 10 minutes of local application of EDTA on 1 side and saline solution on the other side. In the placebo groups, only 1 side was treated (one half of the group with the bur and one half of the group with piezosurgery). All the rats were euthanized at 4 postoperative weeks for comparative histomorphometric evaluation of bone healing in the created defects.
Bone formation was found to be the greatest in the placebo groups (P < .05). Although a greater amount of bone formation was observed with piezosurgery and EDTA among the bisphosphonate-treated groups, the difference between the zoledronate groups was not statistically significant (P > .05). Similarly, no statistically significant difference was found between the use of piezosurgery and conventional bur surgery within the placebo groups (P > .05).
The findings of the present study revealed improved bone healing with the use of piezosurgery and EDTA chelation, although the difference did not reach statistical significance. Further research should be performed to clearly identify the role of EDTA as a chelating agent and in prevention of medication-related osteonecrosis of the jaws development.
Prevalence, initiating factor, and treatment outcome of medication-related osteonecrosis of the jaw—a 4-year prospective study
2018, Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology
Medication-related osteonecrosis of the jaw (MRONJ) has a wide range of prevalence, and a standard therapy has not yet been established. The aim of this study was to analyze the prevalence and initiating factors of MRONJ and the outcomes of surgical therapy.
In a prospective cohort study, all patients diagnosed with MRONJ in the Region of Skåne, in Sweden, were included. Predictor variables (comorbidity, site, stage, gender) and initiating factors (tooth extraction, periodontitis) were recorded. Surgical treatment was sequestrectomy or block resection, and the outcome variable was healing after 2 months. To estimate the prevalence, data on the use of bisphosphonate and denosumab were used.
Fifty-five patients with MRONJ were identified. The prevalence of MRONJ was 0.043% among patients treated with oral bisphosphonates, 1.03% among those on intravenous bisphosphonates and 3.64% in those on high-dose denosumab. Periodontal disease preceded development of MRONJ in 41 patients. Fifty patients were treated surgically and followed up for at least 2 months. Remission or healing occurred in 80% of patients treated with sequestrectomy and in 92.5% of patients treated with block resection.
The prevalence of MRONJ in Sweden is low. Periodontitis is the most common initiating factor. The outcome of treatment of MRONJ is healing in most patients treated surgically.

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Clinical PaperOral MedicineSurgical management of bisphosphonate induced osteonecrosis of the jaws

Abstract

Section snippets

Methods

Results

Discussion

Competing interests

Funding

Ethical approval

J Oral Maxillofac Surg

J Oral Maxillofac Surg

J Oral Maxillofac Surg

J Oral Maxillofac Surg

Clin Geriatr Med

Expert panel recommendations: dental management of patients receiving oral bisphosphonate therapy

J Am Dental Assoc

Osteonecrosis of the jaw in multiple myeloma patients: clinical features and risk factors

J Clin Oncol

Clinical Paper
Oral Medicine
Surgical management of bisphosphonate induced osteonecrosis of the jaws