Bisphosphonate Related Osteonecrosis of the Jaw: A Study of 18 Cases Associated with Fungal Infection

Aftimos, Valérie; Zeinoun, Toni; Tayeh, Rima Bou; Aftimos, Georges

doi:10.1155/2014/869067

Cited by 6 publications

(4 citation statements)

References 25 publications

(31 reference statements)

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“…In OMJ, microorganisms were observed in 50 of the samples, compared to 87.5 and 100 in ORNJ and MRONJ, respectively. Microorganisms of the genus Actinomyces have been found in these diseases by several authors, 6,13,14,15,16 including by Marx and Tursun 2 The microorganisms were detected on trabecular bone surfaces in 76 of MRONJ and in 58 of ORNJ cases. In OMJ samples, these microorganisms were found in medullary spaces.…”

Section: Discussionmentioning

confidence: 98%

Medication-related osteonecrosis of the jaw, osteoradionecrosis, and osteomyelitis: A comparative histopathological study

et al. 2018

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It is largely known that some oral diseases can be diagnosed based upon their clinical manifestation combined with the patient's medical history and generally not depending on examination. This is the case of some bone diseases such as osteoradionecrosis of the jaw (ORNJ), osteomyelitis of the jaw (OMJ), and medication-related osteonecrosis of the jaw (MRONJ). The present study aimed to analyze the histopathological features of these specific bone diseases in order to evaluate similarities and differences. Forty-four bone specimens resected from each bone disease (22 cases of ORNJ, 6 cases of OMJ, and 16 cases of MRONJ) were analyzed by two experienced oral pathologists without prior knowledge of the diagnosis, considering bone tissue condition, inflammation, vascularization, and the presence of microorganisms. In addition, the examiners formulated a diagnostic hypothesis for each specimen. Many histopathological similarities were found among the diseases, especially considering the presence of necrotic bone, inflammation, and microorganisms. Statistically significant differences were detected in empty bone lacunae, which was decreased in ORN (p = 0.042), and considering neutrophil count, which was low in the MRONJ group (p ≤ 0.001). The Kappa coefficient was calculated and agreement was detected based on the histopathological parameters, but not for diagnostic suggestion (p=0.23). In conclusion, histopathological aspects of ORNJ, OMJ, and MRONJ do not permit a conclusive diagnosis, emphasizing the necessity of a detailed clinical report.

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Section: Discussionmentioning

confidence: 98%

Medication-related osteonecrosis of the jaw, osteoradionecrosis, and osteomyelitis: A comparative histopathological study

et al. 2018

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“…Periodontitis is a common inflammatory and infectious disorder in the oral cavity and has been shown to increase the risk of developing BRONJ in humans [22] and animal models [23,24]. Histopathological reports on biopsy samples of BP-related [25] and denosumabrelated [14] ONJ lesions reveal a chronic neutrophil infiltration on the surface of necrotic bone. Thus, aberrant oral barrier immunity may also be associated with the development of MRONJ [26].…”

Section: Introductionmentioning

confidence: 99%

Rescue bisphosphonate treatment of alveolar bone improves extraction socket healing and reduces osteonecrosis in zoledronate-treated mice

Hokugo

Kanayama

Sun

et al. 2019

Bone

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Bisphosphonate (BP)-related osteonecrosis of the jaw, previously known as BRONJ, now referred to more broadly as medication-related osteonecrosis of the jaw (MRONJ), is a morbid condition that represents a significant risk for oncology patients who have received high dose intravenous (IV) infusion of a potent nitrogen containing BP (N-BP) drug. At present, no clinical procedure is available to prevent or effectively treat MRONJ. Although the pathophysiological basis is not yet fully understood, legacy adsorbed N-BP in jawbone has been proposed to be associated with BRONJ by one or more mechanisms. We hypothesized that removal of the pre-adsorbed N-BP drug common to these pathological mechanisms from alveolar bone could be an effective preventative/therapeutic strategy. This study demonstrates that fluorescently labeled BP preadsorbed on the surface of murine maxillo-cranial bone in vivo can be displaced by subsequent application of other BPs. We previously described rodent BRONJ models involving the combination of N-BP treatment such as zoledronate (ZOL) and dental initiating factors such as tooth extraction. We further refined our mouse model by using gel food during the first 7 days of the tooth extraction wound healing period, which decreased confounding food pellet impaction problems in the open boney socket. This refined mouse model does not manifest BRONJ-like severe jawbone exposure, but development of osteonecrosis around the extraction socket and chronic gingival inflammation are clearly exhibited. In this study, we examined the effect of benign BP displacement of legacy N-BP on tooth extraction wound healing in the in vivo model. Systemic IV administration of a low potency BP (lpBP: defined as inactive at 100 μM in a standard protein anti-prenylation assay) did not significantly attenuate jawbone osteonecrosis. We then developed an intra-oral formulation of lpBP, which when injected into the gingiva adjacent to the tooth prior to extraction, dramatically reduced the osteocyte necrosis area. Furthermore, the tooth extraction wound healing pattern was normalized, as evidenced by timely closure of oral soft tissue without epithelial hyperplasia, significantly reduced gingival inflammation and increased new bone filling in the extraction socket. Our results are consistent with the hypothesis that local application of a rescue BP prior to dental surgery can decrease the amount of a legacy N-BP drug in proximate jawbone surfaces below the threshold that promotes osteocyte necrosis. This observation should provide a conceptual basis for a novel strategy to improve socket healing in patients treated with BPs while preserving therapeutic benefit from anti-resorptive N-BP drug in vertebral and appendicular bones.

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“…Actinomycosis has been linked to the disease of osteonecrosis of the jaw in several studies [ 3 , 6 , 12 , 13 , 14 , 15 , 16 ]. The mainstay of actinomycosis management is prolonged antimicrobial treatment.…”

Section: Discussionmentioning

confidence: 99%

Actinomyces sp. Presence in the Bone Specimens of Patients with Osteonecrosis of the Jaw: The Histopathological Analysis and Clinical Implication

et al. 2022

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Medication-related osteonecrosis of the jaw (MRONJ) and osteoradionecrosis (ORN) are two similar bone pathologies in the jaw with different aetiologies. Actinomycosis is a relatively rare oral infection caused by the Gram-positive anaerobe Actinomyces sp. that normally colonizes the oral cavity. Actinomycosis is associated with the pathogenesis of both the MRONJ and ORN, as evident in our cases, and not just as a superficial contaminant. The clinical and histopathological aspects of the cases treated in our centre were also reported with a review of the literature. Clinical implication on the treatment of the cases was highlighted in view of the presence of this microorganism.

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Bisphosphonate Related Osteonecrosis of the Jaw: A Study of 18 Cases Associated with Fungal Infection

Cited by 6 publications

References 25 publications

Medication-related osteonecrosis of the jaw, osteoradionecrosis, and osteomyelitis: A comparative histopathological study

Medication-related osteonecrosis of the jaw, osteoradionecrosis, and osteomyelitis: A comparative histopathological study

Rescue bisphosphonate treatment of alveolar bone improves extraction socket healing and reduces osteonecrosis in zoledronate-treated mice

Actinomyces sp. Presence in the Bone Specimens of Patients with Osteonecrosis of the Jaw: The Histopathological Analysis and Clinical Implication

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