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What are the current theories on the etiology of MRONJ and what is the importance of infection in its development?

This summary is based on the article published in the Journal of Dental Research: Infection and Medication-related Osteonecrosis of the Jaw (April 2015)

Katsarelis, N.P. Shah, D.K. Dhariwal, and M. Pazianas


  • Medication-related osteonecrosis of the jaw (MRONJ), althougJawh initially believed to be exclusively associated with bisphosphonates, has been implicated in recent reports with additional drugs, especially the bone antiresorptive denosumab.
  • The pathophysiology has not been fully elucidated, and no causal association between bone antiresorptive regimens and MRONJ has yet been established. However, reduced bone turnover and infection, an almost universal finding, are thought to be central to the pathogenesis of MRONJ.
  • Both bisphosphonates and denosumab, through different pathways of action, significantly reduce the rate of bone turnover and potentially reduce the efficacy of the host defense against infection.
  • Recent evidence questions the simplified etiology of low bone turnover causing MRONJ and offers evidence on the prominent role of infection instead.
  • The management of MRONJ remains a significant clinical challenge, with little progress having been made on treatment.

Purpose of the Article

To explore the current theories on the etiology of MRONJ and to emphasize the importance of infection in the development of this devastating pathology.

Key Findings

  • Compromised local defense due to insufficient numbers or reduced functional capacity of macrophages locally could allow oral pathogens to reach the bone surface in the jaws.
  • The presence of the infectious component of ONJ, regardless if it comes first or develops later, is the most horrifying aspect of the ONJ, significantly affecting the quality of life of these patients. Oral pathogens should be prevented from reaching the bone surface, and optimum oral hygiene is essential.
  • The current regimens—which consist of oral antiseptics in the early stages, with the addition of antibiotics in more advanced stages—are not always successful.
  • Ideally, treatment aims to eradicate the underlying infection, prevent secondary infection, stop the disease process, and control symptoms (McLeod et al 2011).
  • Traumatic intervention should be avoided, but where it must be undertaken, strict adherence is necessary per the guidelines of the American Association of Oral and Maxillofacial Surgeons and International Task Force on Osteonecrosis of the Jaw.
  • The proposed sequence of events in the development of ONJ with infection at the epicenter could justify temporary discontinuation of the “offending drug” to allow recovery of macrophage production and function.


List of references (PDF)

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