Methotrexate-associated osteonecrosis of the jaw: A report of two cases

Henien, Marianne; Carey, Barbara; Hullah, Esther; Sproat, Chris; Patel, Vinod

doi:10.1016/j.oooo.2017.09.005

Cited by 38 publications

(20 citation statements)

References 30 publications

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“…While BPs, denosumab, bevacizumab, and sunitinib were identified as causative agents of MRONJ in the AAOMS 2014 report, additional studies have indicated that ONJ can be caused by single agent of corticosteroids [9], [10], methotrexate [11], [12], and recreational or illicit drugs such as cocaine, amphetamine, and methamphetamine [13], [14]. Because corticosteroids and methotrexate are also commonly used in conjunction with BPs or denosumab, it is important to check an accurate medical past history and history of drug use for all patients.…”

Section: Recent Evidencementioning

confidence: 99%

Novel insight into the management of bisphosphonate-related osteonecrosis of the jaw (BRONJ)

Kishimoto

Noguchi

Takaoka

2019

Japanese Dental Science Review

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Summary Bisphosphonate-related osteonecrosis of the jaw (BRONJ), characterized by refractory bone exposure, has recently emerged as a serious side effect of bisphosphonate (BPs) treatment. We discuss novel insights that may help to improve the efficacy of BRONJ treatment and prevention. Our report highlights the following: (1) The presence of exposed bone in patients taking BPs does not necessarily reflect BRONJ, and diagnoses of oral ulceration with bone sequestration and malignancy must be excluded. (2) Osteonecrosis type of BRONJ is difficult to avoid using preventive dental measures alone. However, as with osteomyelitis type of BRONJ, preventive dental measures are indispensable for reducing the risk of secondary infection and disease progression. (3) The importance of tooth extraction as a risk factor for BRONJ among patients taking BPs has been overstated, particularly when they are administered at low doses. Delaying tooth extraction may increase the risk for the onset and progression of osteomyelitic BRONJ. (4) In patients taking low doses of BPs, dental implant surgery is not necessarily contraindicated if there are no other risk factors, such as combined use of corticosteroids or concomitant diabetes. However, the risk of BRONJ due to peri-implantitis must be explained when obtaining patient consent.

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Section: Recent Evidencementioning

confidence: 99%

Novel insight into the management of bisphosphonate-related osteonecrosis of the jaw (BRONJ)

Kishimoto

Noguchi

Takaoka

2019

Japanese Dental Science Review

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“…It has been reported in the AAOMS paper and the International Taskforce on ONJ that the use of glucocorticoids are a confounding variable that can increase a patient's risk of MRONJ, due to their well‐documented effects on bone, including inhibition of wound formation in bone and soft tissue, and increased apoptosis of osteoblasts and osteocytes 36,37 . Dexamethasone, prednisolone, mycophenolate and cyclophosphamide were all listed as concurrent medications in the DAEN, as well as cytotoxic antineoplastics such as cyclophosphamide, docetaxel, paclitaxel and gemcitabine.…”

Section: Discussionmentioning

confidence: 99%

Medication‐related osteonecrosis of the jaw: Analysing the range of implicated drugs from the Australian database of adverse event notifications

Teoh

Moses

Nguyen

et al. 2020

Brit J Clinical Pharma

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Aims Medication‐related osteonecrosis of the jaw (MRONJ) is an uncommon but potentially debilitating condition, characterised by nonhealing jawbone, with or without mucosal exposure, in the presence of certain drugs. Those already strongly associated with MRONJ include antiresorptives denosumab and bisphosphonates; however, a growing range of other non‐antiresorptive drugs is implicated. The aim of this study was to analyse all case reports of MRONJ submitted to the publicly available Database of Adverse Event Notification from the Therapeutic Goods Administration in Australia. Methods The Therapeutic Goods Administration was contacted on 6 January 2020 and asked for all reports containing the words “osteonecrosis of the jaw”. This was provided in a spreadsheet of de‐identified reports received from commencement of the database in 1971 until 1 October 2019. Results The drugs implicated in the 419 cases were divided by established drugs with MRONJ and secondary drugs that possibly contribute to MRONJ development. While the majority of cases were associated with denosumab or bisphosphonates (n = 405), there were 14 reports where secondary agents that directly or indirectly affect bone turnover, were also implicated. Some of these secondary drugs, including adalimumab, etanercept, methotrexate and rituximab have previously been associated with MRONJ in published case reports. Conclusions This study contributes to the sparse but growing literature associating an increasing number of drugs with MRONJ, and underscores the importance of considering all possible drugs that elevate a patient's MRONJ risk.

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“…On the other hand, in some cases, the presence of necrotic bone could be secondary to a Methotrexate-related chronic lymphoproliferative disorder and it would therefore be arguable whether it should be considered as MRONJ, in the absence of a detailed histopathological study of the lesion (71). However, authors such as Henien et al (72), have recently described cases of MRONJ in patients treated for RA with low oral doses of MTX over long periods of time, in the absence of a lymphoproliferative disorder and with no administration of other antiresorptive or antiangiogenic medications. The exact etiopathogenic mechanism of its possible association with MRONJ is unknown, although it appears to be primarily associated with its immunomodulating effects.…”

Section: Active Ingredientmentioning

confidence: 99%

Review and update on drugs related to the development of osteonecrosis of the jaw

Eguia¹,

Bagán-Debón²,

Cardona³

2020

Med Oral

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Background: Medication-related osteonecrosis of the jaw (MRONJ) is a rare, but serious adverse effect of certain drugs, of which bisphosphonates are the most widely known. This pathology is also associated with other medications such as the biologic antiresorptive agent, denosumab and some antiangiogenics such as sunitinib, bevacizumab or aflibercept. Very recently, new medications have also been associated with osteonecrosis of the jaw (ONJ). The objectives were to update the list of medications associated with ONJ, to analyze the fundamental aspects of this list and to describe the level of evidence available. Material and Methods: A narrative bibliographic review was made, using the PubMed-MedLine, DOAJ and SCI-ELO databases. Additional information was obtained through the online Medication Information Centre of the Spanish Agency of Medicines and Medical Devices (AEMPS-CIMA), the websites of the US Food & Drugs Administration (Drugs@FDA) and the European Medicines Agency (EMA). Results: The latest drugs identified as potential facilitators of this pathology include a number of anti-VEGF based antiangiogenic drugs and anti-TKI and different types of immunomodulators. Neither the level of evidence in this association nor the risk are equal for all these drugs. On the other hand, over the coming years, new drugs will be marketed with similar action mechanisms to those that are recognized as having this adverse effect. Conclusions: No effective therapy is currently known for the treatment of ONJ. Therefore, in order to prevent new cases of MRONJ, it is essential for all oral healthcare professionals to be fully up-to-date with the etiopathogenic aspects of this pathology and to be aware of those drugs considered to be a risk.

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Methotrexate-associated osteonecrosis of the jaw: A report of two cases

Cited by 38 publications

References 30 publications

Novel insight into the management of bisphosphonate-related osteonecrosis of the jaw (BRONJ)

Novel insight into the management of bisphosphonate-related osteonecrosis of the jaw (BRONJ)

Medication‐related osteonecrosis of the jaw: Analysing the range of implicated drugs from the Australian database of adverse event notifications

Review and update on drugs related to the development of osteonecrosis of the jaw

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