Surgical treatment of medication-related osteonecrosis of the jaws: UPDATE 2018

Background: The more recent position papers on medication-related osteonecrosis of the jaws (MRONJ) have been issued by American Association of Oral and Maxillofacial Surgeons in 2014 and by Japanese Allied Committee on Osteonecrosis of the Jaws in 2017; nevertheless to date no official guidelines are available for the management of patients with MRONJ; the existing management directions are mostly the result of the experience of specialized centers and even if stage-specific therapy has reached general agreement, precise treatment guidelines for the surgical approach have not been drawn. Interventions range from conservative debridement to major resection, often without a precise definition or description of the extent of bone removal. The ideal would be to reach a consensus, defining case features and details of the required intervention (e.g., debridement, conservative resection, or segmental resection). Methods: a narrative review of the lasts four years literature on the topic of surgical treatment of medication-related osteonecrosis was performed. Results: in the indicated period about eighty studies were published. Several of them were excluded after a careful reading of the abstract. The identified studies mainly focused on bisphosphonates rather than on denosumab or other oncologic drugs (Pichardo 2016, Hoefert 2017). Analyzing in brief the noteworthy aspects, most of the studies were retrospective analyzes (Hoefert 2017, Kim 2017, Hayashida 2017, Eguchi 2017, Zirk 2017, Voss 2016, Nisi 2016, Pichardo 2016). In most cases the patient cohort was limited and some were case series (Pichardo 2016). The majority of prospective studies aimed to investigate the use of healing promoters such as bone marrow mesenchymal stem cells (MScs) (Voss2017), bovine lactoferrin (Calvani 2018), leukocyte (Maluf 2018), platelet- rich plasma (PrP) (Fornaini 2017) and platelet-rich fibrin (PrF) (Maluf 2018, Inchingolo 2017, Park 2017, Nørholt 2016). Other studies reported advanced surgical techniques such as repositioning flaps (lemound 2018). Systematic reviews did not include randomized clinical trials or case and control studies (ramaglia 2017) therefore the collected data are not enough to draw definite conclusions. Moreover other reviews, although published recently, were referred to papers published before 2014 (Silva 2016). In the considered studies cancer and osteoporotic patients were often included in the same analyzed cohorts. The issues of peri- operative antibiotic therapy and drug holiday were poorly addressed. All stages have been considered but except for Kim (2017) and Zirk (2017) studies did not include a comparison between the different possible surgical techniques. In general, the surgical outcome was evaluated in terms of clinical wound healing without dehiscence or evidence of recurrence (Blus 2017, Bodem 2016, Klingelhöffer 2016). Only few studies addressed the symptomatology related to Mr-oNJ (Blus 2017) or the impact of treatment on patient’s quality of life (oteri 2018). Conclusions. Considerations deriving from this revision underline the approach oriented towards surgical treatment in all MRONJ stages and the need to conduct larger clinical studies in terms of number of patients and follow-up periods, to provide clear indications about surgical treatment of MRONJ and its prognostic parameters.