Infection and Medication-related Osteonecrosis of the Jaw

Katsarelis, Helen; Shah, Neha; Dhariwal, Daljit; Pazianas, Michael

doi:10.1177/0022034515572021

Cited by 127 publications

(101 citation statements)

References 50 publications

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“…Alternatively, the presence of osteonecrosis in the maxilla and mandible could be because of a unique response of the jaws versus other bones to the harmful inflammatory environment. Such a heightened sensitivity could explain the near exclusive presentation of ONJ in the jaws compared with the remaining skeleton …”

Section: Discussionmentioning

confidence: 99%

Rheumatoid Arthritis Exacerbates the Severity of Osteonecrosis of the Jaws (ONJ) in Mice. A Randomized, Prospective, Controlled Animal Study

Molon

Hsu

Bezouglaia

et al. 2016

Journal of Bone and Mineral Research

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Rheumatoid arthritis (RA), an autoimmune inflammatory disorder, results in persistent synovitis with severe bone and cartilage destruction. Bisphosphonates (BPs) are often utilized in RA patients to reduce bone destruction and manage osteoporosis. However, BPs, especially at high doses, are associated with osteonecrosis of the jaw (ONJ). Here, utilizing previously published ONJ animal models, we are exploring interactions between RA and ONJ incidence and severity. DBA1/J-mice were divided in 4 groups: control, zoledronic acid (ZA), collagen induced arthritis (CIA), and CIA-ZA. Animals were pre-treated with vehicle or ZA. Bovine collagen II emulsified in Freund’s adjuvant was injected to induce arthritis (CIA) and the mandibular molar crowns were drilled to induce periapical disease. Vehicle or ZA treatment continued for 8-weeks. ONJ indices were measured by micro-CT and histological examination of maxillae and mandibles. Arthritis development was assessed by visual scoring of paw swelling, and by micro-CT and histology of interphalangeal and knee joints. Maxillae and mandibles of control and CIA mice showed bone loss, PDL space widening, lamina dura loss and cortex thinning. ZA prevented theses changes in both ZA and CIA-ZA groups. Epithelial to alveolar crest distance was increased in the control and CIA mice. This distance was preserved in ZA and CIA-ZA animals. Empty osteocytic lacunae and areas of osteonecrosis were present in ZA and CIA-ZA but more extensively in CIA-ZA animals, indicating more severe ONJ. CIA and CIA-ZA groups developed severe arthritis in the paws and knees. Interphalangeal and knee joints of CIA mice showed advanced bone destruction with cortical erosions and trabecular bone loss, and ZA treatment reduced these effects. Importantly, no osteonecrosis was noted adjacent to areas of articular inflammation in CIA-ZA mice. Our data suggest that ONJ burden was more pronounced in ZA treated CIA mice and that RA could be a risk factor for ONJ development.

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Section: Discussionmentioning

confidence: 99%

Rheumatoid Arthritis Exacerbates the Severity of Osteonecrosis of the Jaws (ONJ) in Mice. A Randomized, Prospective, Controlled Animal Study

Molon

Hsu

Bezouglaia

et al. 2016

Journal of Bone and Mineral Research

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“…1. 25 MRONJ is more prevalent and severe in patients with comorbidities such as cancer or immunosuppression, and clinical suppuration and oral trauma have been shown to be independent risk factors for disease onset. 26 MRONJ is also known to be associated with bacterial biofilms, making treatment more challenging.…”

Section: Discussionmentioning

confidence: 99%

Opportunistic Oral Infections

Sedghizadeh

Mahabady

Allen

2017

Dental Clinics of North America

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An opportunistic infection (OI) is a disease of microbial cause or pathogenesis generally thought to occur in hosts with weakened immunity. Oral OIs are associated with many risk factors and pathogens. Causative organisms for oral OIs have unique modes of transmission. The clinical presentation of oral OIs is heterogeneous and diagnosis can be challenging. Therefore, laboratory identification of causative pathogens is useful for definitive diagnosis and targeted therapeutics, and can be achieved by biological, serologic, histologic, and/or molecular methods. Clinical risk assessment and history with review of systems, and accurate diagnosis, treatment, and follow-up, are essential.

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“…Recent studies have revealed the presence of Actinomyces colonies in biopsy material from patients with MRONJ, suggesting that these bacteria contribute to MRONJ-associated infections (2,45,46). Members of the Actinomyces genus are filamentous, gram-positive and anaerobic bacteria that typically colonize the mouth, colon and vagina.…”

Section: Discussionmentioning

confidence: 99%

Denosumab-related osteonecrosis of the jaw in a patient with bone metastases of prostate cancer: A case report and literature review

et al. 2017

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Denosumab, a human monoclonal antibody directed against the receptor activator of nuclear factor-κβ ligand (RANKL), is used for the treatment of patients with metastatic cancer of the bone or osteoporosis. Recent reports have demonstrated that denosumab can induce osteonecrosis of the jaw (ONJ), but reported cases of this are uncommon. The present study reports the case of an 86-year-old male with prostate cancer patient exhibiting bone metastases who developed ONJ whilst receiving denosumab. To elucidate the influence of denosumab on the development of ONJ, the present study also reviewed the literature, including clinical trials and case reports. In the clinical trials, the prevalence of denosumab-related ONJ was higher in patients with cancer compared with those with osteoporosis. The high risk of ONJ in patients with cancer was thought to be associated with the differing dose and frequency of denosumab administration. The prevalence of ONJ was not significantly different between patients receiving denosumab and bisphoshonate (BP). In the reported cases, denosumab-related ONJ had a similar clinical presentation to BP-related ONJ. There was also a tendency for denosumab-related ONJ to develop in the mandible of elderly patients. Previous invasive dental treatment was a commonly shared characteristic of patients with denosumab-related ONJ. A complex medical history was also suspected to affect the prevalence. No clear association between the dose or duration of denosumab treatment and the development of ONJ was observed. Although conservative treatments are given for denosumab-related ONJ, non-improving cases were managed surgically with primarily positive results. Because denosumab may offer superior results compared with BP for the treatment of metastatic cancer of the bone or osteoporosis, the use of denosumab is expected to increase in the near future. Clinicians should also be aware of the risk factors for denosumab-related ONJ, in order to aid in its diagnosis. In addition, patients treated with denosumab should receive prophylactic treatment to maintain their oral health prior to, during and after denosumab treatment.

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Infection and Medication-related Osteonecrosis of the Jaw

Cited by 127 publications

References 50 publications

Rheumatoid Arthritis Exacerbates the Severity of Osteonecrosis of the Jaws (ONJ) in Mice. A Randomized, Prospective, Controlled Animal Study

Rheumatoid Arthritis Exacerbates the Severity of Osteonecrosis of the Jaws (ONJ) in Mice. A Randomized, Prospective, Controlled Animal Study

Opportunistic Oral Infections

Denosumab-related osteonecrosis of the jaw in a patient with bone metastases of prostate cancer: A case report and literature review

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