Identification of Microbial Biofilms in Osteonecrosis of the Jaws Secondary to Bisphosphonate Therapy

doi:10.1016/j.joms.2007.11.035

Journal of Oral and Maxillofacial Surgery

Volume 66, Issue 4, April 2008, Pages 767-775

https://doi.org/10.1016/j.joms.2007.11.035 Get rights and content

Purpose

Biofilm theory has emerged to explain the etiology of the chronic infections that have come to constitute between 65% to 80% of the microbial diseases treated by physicians in the developed world. The purpose of this article is to report for the first time the observation of multispecies microbial biofilms on affected bone in patients with osteonecrosis of the jaws (ONJ) secondary to bisphosphonate therapy.

Patients and Methods

A program has been established at the University of Southern California to monitor and evaluate patients with ONJ as a multidisciplinary collaboration between the School of Dentistry, Center for Biofilms, Center for Craniofacial Molecular Biology and the Keck School of Medicine. From this cohort, 4 patients with active ONJ who were scheduled for necessary treatment in the form of sequestrectomy gave informed consent for this study. Bone samples were evaluated using conventional histopathologic techniques and scanning electron microscopy, a technique applicable to biofilm characterization.

Results

Bone specimens from affected sites in all patients showed large areas occluded with biofilms comprising mainly bacteria, and occasionally yeast, embedded in extracellular polymeric substance. The number of bacterial morphotypes in the biofilms ranged from 2 to 15, and they included species from the genus Fusobacterium, bacillus, actinomyces, staphylococcus, streptococcus, Selenomonas, and 3 different types of treponemes. The yeast identified was consistent with Candida species. Co-aggregation was observed between different species within the biofilms.

Conclusion

These findings have important clinical and therapeutic implications and may suggest a role for microbial biofilms in the disease process of ONJ.

Section snippets

Patients and Methods

Appropriate Institutional Review Board (IRB) approval was obtained for this study. A program has been established at the University of Southern California to monitor and evaluate patients with ONJ as a multidisciplinary collaboration between the School of Dentistry, Center for Biofilms, Center for Craniofacial Molecular Biology and the Keck School of Medicine. From this cohort, 4 patients with active ONJ (Table 1) who were scheduled for necessary treatment in the form of surgical debridement of

Results

Bone specimens from affected sites in all patients evaluated by SEM showed large areas occluded with biofilms comprising mainly bacteria, and occasionally yeast, embedded in extracellular polymeric substance; control bone tissue was unremarkable. Routine histopathologic examination was inadequate for the identification of biofilm bacteria even at high-power magnification. The number of distinguishable bacterial morphotypes observed in the biofilms ranged from 2 to 15. They included species from

Discussion

This is the first report showing evidence of microbial biofilms in the bone of patients affected by ONJ, and this is the first time that bone specimens from this condition have been examined by SEM, a method applicable to biofilm evaluation in addition to allowing characterization of bone morphology and topography. The organisms identified are consistent with microbial flora found in the oral cavity, particularly during pathologic states such as periodontal, pulpal, periapical (bacterial), and

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The objective of this study was to identify the prevalence of osteonecrosis of the jaw in a pediatric population with systemic therapeutic exposure to an antiresorptive, anti-angiogenic, and/or immunomodulating drug (ARAID), and in particular in the subgroup of patients who had undergone invasive dental treatment. This was a retrospective cohort study performed at a single center. The investigation included pediatric patients who had undergone systemic therapy with ARAIDs and who began receiving ARAID therapy at ≤16 years of age. The study included 482 patients who received ARAIDs between January 2011 and January 2021. The most common medication class was bisphosphonates (45.0%), followed by mTOR inhibitors (30.1%) and anti-angiogenics (17.8%). No diagnosis of osteonecrosis of the jaw was observed. From this population, 26 patients were noted to have undergone invasive dental treatment. The duration from treatment to the invasive procedure ranged from 0 to 5.9 years. Medication-related osteonecrosis of the jaw is extremely rare among the pediatric population – much less common when compared to the adult population. Prospective cohort studies and continued evaluation will help determine the incidence and prevalence of medication-related osteonecrosis of the jaw in pediatric patients.
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Consensus has not yet been reached on the therapy for medication-related osteonecrosis of the jaw (MRONJ). We assessed the effectiveness of conservative surgical management, which involves removing the necrotic bone and performing a gingivectomy, followed by localized cleaning to facilitate the separation of the sequestrum. Additionally, we revalidated the treatment algorithm utilized by our department.
We examined 160 patients diagnosed with MRONJ at three hospitals. The data for this study were collected retrospectively. These patients were followed up for a minimum of 2 years.
The outcome 2 years after starting conservative surgical management was: cure: 117 cases; improvement: 22 cases; unchanged: 12 cases; and deterioration: 9 cases. The cure rate was 72.3% and 83.0% at 2 and 5 years after therapy initiation, respectively, and significantly lower at age ≥ 74 years compared to age < 74 years (P < 0.001), with malignant tumour as the primary disease when compared to osteoporosis (P < 0.001), and with ≥ 4 years of administration compared to < 4 years (P = 0.0301). On multivariate analysis, the trigger (P < 0.05), primary disease (P = 0.001), and administration period (P < 0.01) were independent prognostic factors.
Conservative surgical management is effective for MRONJ regardless of stage, especially in patients with age < 74 years, osteoporosis, and short drug-administration periods, and could become a first-line therapy for all stages.
Actinomycosis and osteonecrosis of the jaw: Every why hides a why
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High through-put sequencing analysis of changes in oral flora in rats before and after zoledronate administration
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The aim of this study was to compare the changes in the oral flora of Sprague-Dawley rats before intraperitoneal injection of zoledronic acid, 6 weeks and 12 weeks after injection. Clinically, some antibiotics effectively treat patients with medicine-related osteonecrosis of the jaws (MRONJ), but the effect of broad-spectrum antibiotics for osteomyelitis of the jaw is not obvious. We therefore speculated that MRONJ may have some dominant bacteria. We used 12 healthy rats for the experiment. One rat was used for haematoxylin and eosin staining, three were used for gene analysis, three for signal molecule research, and five for 16SrDNA high-pass sequencing to compare the changes of flora before intraperitoneal injection of zoledronic acid, and 6 and 12 weeks after injection once every three days. Alpha and beta analysis was used for sequencing data. Analysis of the flora showed that the alpha diversity of the bacteria of rats injected with zoledronic acid was significantly higher than it was before injection (p < 0.05). At the phylum level, Bacteroidetes at 6 and 12 weeks of injection were significantly higher than those before injection (p < 0.05). At the genus level, the proportions of Novophingobium, Dubosiella, Mannheimia, Prevotella, Brevundimonas, and Bacteroides were higher than they were before injection (p < 0.05). The proportions of Lactobacillus, Mannheimia, Brevundimonas, Bacteroides, Roseovarius, Salegentibacter, Marinobacter, and Granulicatella in rats injected for 12 weeks were higher than those before injection (p < 0.05). Zoledronic acid can change the structure of oral flora in SD rats, in which Bacteroides increased and Actinomycetes decreased.
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The AAOMS in 2014 changed from BRONJ to the term Medication-Related Osteonecrosis of the Jaw (MRONJ), because of the growing number of osteonecrosis cases associated with other antiresorptive and antiangiogenic therapies. Even if the drugs involved are different, the histopathological findings are the same. Colonies of Actinomyces are encountered in most cases. The aim of the present study is to report on Actinomyces prevalence among the cases of MRONJ, taking into consideration also antiresorptive and antiangiogenic therapies in the literature and in our sample between 2005 and 2020.
The review was performed using the database Medline the linkage between Actinomyces infection and MRONJ. The retrospective study was conducted on patients between with clinical and radiological manifestations of MRONJ May 2005 and February 2020.
A total of 42 articles were found, 30 publications have been taken into consideration for the review. A total of 114 patients have been examined at the Padua Hospital. A total of 101 oncological patients presented the histological confirmation of MRONJ. 83 specimens revealed the presence of Actinomyces infection (82.18%).
Actinomyces-associated lesions are frequent and present a wide spectrum of clinical manifestation.
Can medication-related osteonecrosis of the jaw be attributed to specific microorganisms through oral microbiota analyses? A preliminary study
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Basic and patient-oriented researchIdentification of Microbial Biofilms in Osteonecrosis of the Jaws Secondary to Bisphosphonate Therapy

Purpose

Patients and Methods

Results

Conclusion

Section snippets

Patients and Methods

Results

Discussion

Lancet

Semin Arthritis Rheum

Oral Surg Oral Med Oral Pathol Oral Radiol Endod

J Oral Maxillofac Surg

Lancet Oncol

Biofilm theory can guide the treatment of device-related orthopedic infections

Clin Orthop Rel Res

Engineering approaches for the detection and control of orthopaedic biofilm infections

Clin Ortho Rel Res

Biofilms and antimicrobial resistance

Clin Ortho Rel Res

Biofilms: Survival mechanisms of clinically relevant microorganisms

Clin Microbiol Rev

Bacterial biofilms: A common cause of persistent infections

Science

Evaluation of nonculture methods for the detection of prosthetic hip biofilms

Clin Ortho Rel Res

Basic and patient-oriented research
Identification of Microbial Biofilms in Osteonecrosis of the Jaws Secondary to Bisphosphonate Therapy