Proceedings of the Closed Round Table and Italian Consensus on the Medication-Related Osteonecrosis of Jaws (MRONJ) at the Symposium of Italian Society of Oral Pathology and Medicine (SIPMO) Ancona, 20 October 2018 - Part I

• ¹ University of Palermo, Italy
• ² University of Padova, Italy
• ³ University of Verona, Italy
• ⁴ University of Trieste, Italy
• ⁵ Second University of Naples, Italy
• ⁶ University of Modena and Reggio Emilia, Italy
• ⁷ University of Bari Aldo Moro, Italy
• ⁸ Azienda Ospedaliera Nazionale SS. Antonio e Biagio e Cesare Arrigo, Italy
• ⁹ University of Pisa, Italy
• ¹⁰ University of Foggia, Italy
• ¹¹ University of Messina, Italy
• ¹² University of Parma, Italy
• ¹³ University of Naples Federico II, Italy
• ¹⁴ Sapienza University of Rome, Italy
• ¹⁵ Polytechnical University of Marche, Italy

On 20 October 2018 a Closed Round Table brought together a wide range of stakeholders from several medical disciplines, including academic experts, dentists, oncologists, maxillo-facial surgeons, oral surgeons, radiologists, under the technical and scientific coordination of Giuseppina Campisi (for SIPMO) and Giacomo Oteri (for Italian Society of Oral Surgery- SIdCO). This closed Round Table is successive to the Open Meeting on the same topic held in Rome (14 April 2018) when opinions were discussed and synthesized by the following 22 Italian experts, all equally contributed and labeled as MRONJ Italian Consensus: - Bedogni Alberto (University of Padua) - Bertoldo Francesco (University of Verona) - Bettini Giordana (University of Padua) - Biasotto Matteo (University of Trieste) - Campisi Giuseppina (University of Palermo) - Colella Giuseppe (Second University of Naples) - Consolo Ugo (University of Modena and Reggio Emilia) - Di Fede Olga (University of Palermo) - Favia Gianfranco (University of Bari) - Fusco Vittorio (SS Antonio e Biagio e Cesare Arrigo Hospital of Alessandria) - Gabriele Mario (University of Pisa) - Lo Casto Antonio (University of Palermo) - Lo Russo Lucio (University of Foggia) - Marcianò Antonia (University of Messina) - Mauceri Rodolfo (University of Palermo) - Meleti Marco (University of Parma) - Mignogna Michele Davide (University of Naples Federico II) - Oteri Giacomo (University of Messina) - Panzarella Vera (University of Palermo) - Romeo Umberto (Sapienza University of Rome) - Santarelli Andrea (Marche Polytechnic University) - Vescovi Paolo (University of Parma) The main issues addressed, within both the above open and the closed round tables, were: 1. Practices at risk of inappropriateness in clinical diagnosis of MRONJ and good practices 2. Practices at risk of inappropriateness in radiologic diagnosis of MRONJ and good practices 3. Practices at risk of inappropriateness in prevention of MRONJ and good practices 4. Practices at risk of inappropriateness in dental management and good practices for patients at risk of MRONJ 5. Practices at risk of inappropriateness in Drug Holiday (temporary suspension vs therapeutic suspension for patients at risk of MRONJ). Yes vs No 6. Practices at risk of inappropriateness in MRONJ therapy and good practices During the open meeting, the statements that the authors submitted for each issue were evaluated and some motivated changes to the proposal were approved in consensus; the process involved 22 Italian experts of MRONJ. As a serious moment for public debate, the discussions held during the Open Meeting in Rome (14 April 2018) were also transcribed. The methodology adopted, for these open and closed round tables, was derived and modified from Choosing Wisely where it is mandatory to identify and intercept all unnecessary tests, treatments and procedures, beginning from what not to do, and to distinguish those strictly appropriate [1–3]. These theoretical bases were posed in 2010 by the American Board of Internal Medicine (ABIM) Foundation that launched the project “Choosing Wisely” (www.choosingwisely.org) with the major endpoint to reduce inadequate medical practices to ensure more accurate diagnoses and avoid the waste of limited resources. The Italian Consensus on MRONJ established that, within the 6 issues, for any inappropriate practice, with the same “#” code, the recommended practical equivalent will be found. The aim of the present publication is to briefly present what was discussed and approved in consensus in Rome (14 April 2018) and illustrated in Ancona (20 October 2018), to promote dissemination strategies and to outline the impact of the concepts defined “appropriate” in the ONJ prevention and therapy in the NHS practice. A. Practices at risk of inappropriateness in CLINICAL DIAGNOSIS of MRONJ and good practices The Italian Consensus on the Medication-Related Osteonecrosis of Jaws (MRONJ) adopted from the ONJ SIPMO board the following definition of MRONJ “adverse drug reaction described as the progressive destruction and death of bone that affects the mandible and maxilla of patients exposed to the treatment with medications known to increase the risk of disease, in the absence of a previous radiation treatment” [4](https://www.qeios.com/read/definition/345), to be diagnosed and scored by clinics and radiographs; nevertheless the presence of exposed necrotic bone or bone probing via sinus/fistula tracts for more than 8 weeks (see figures 1,2,3) [5–10]. Practices at risk of inappropriateness #1 restricting the anamnestic interview only to the assumption of bisphosphonates for diagnosing MRONJ. #2 carrying out routine bone biopsies when suspecting a MRONJ. #3 considering the presence of exposed necrotic bone, in the oral cavity, as an essential (conditio sine qua non) sign to diagnose MRONJ. #4 judging the presence of pain as an essential symptom for diagnosing MRONJ. #5 believing that all MRONJ are preceded by dental invasive procedures. Good practices #1 evaluate not only the intake of bisphosphonate drugs, but also further (current and past) pharmacological therapies (e.g. anti-resorptive agents or drugs with anti-angiogenic activity) and perform a thorough physical examination and medical history, together with targeted radiologic examinations (see second paragraph). #2 perform jaws bone biopsies only if there is a suspicion of metastases in cancer patients. #3 take into the account not only the presence of exposed necrotic bone, but also to consider other clinical signs and first/second level imaging. #4 consider that the symptom pain may not always be present in all MRONJ cases, especially in the early stages. #5 consider that some cases of MRONJ can arise spontaneously or by dental-periodontal diseases, without relation to previous dental invasive procedures. B. Practices at risk of inappropriateness in RADIOLOGIC DIAGNOSIS of MRONJ and good practices Radiologic imaging is a fundamental tool for diagnostic accomplishment, definition of the extent of disease at the skeletal level, and subsequently staging of the disease with the correct therapeutic planning (see figures 1,2,3). Although no specific radiological signs of disease can be defined until now, an increasing volume of evidence recognizes some radiological characteristics that, although non-specific, are associated with MRONJ. The use of radiological procedures must be aimed at the diagnostic/therapeutic advantage, in order to reduce high social and biological costs deriving from radiation exposure [11]. MRONJ is a pathological process that originates at the skeletal level and which only partially affects the soft tissues, so it requires targeted imaging methods for diagnostic definition. MRONJ is a pathological process that originates at the skeletal level and which only partially affects the soft tissues, so it requires targeted imaging methods for diagnostic definition (e.g. panoramic dental x-ray and CT scan, defined I and II level exams, respectively). Only in cases of doubtful diagnosis it may be useful to resort to additional investigations such as MRI and PET-CT (III level exams), unless they are to be performed to monitor neoplastic disease, therefore not specifically prescribed for MRONJ diagnosis. Practices at risk of inappropriateness #1 starting therapies at risk of MRONJ without a radiologic assessment of dental arches, remarkably in cancer patients. #2 prescribing to everybody exposed to therapies at risk of MRONJ all imaging techniques to rule out MRONJ. #3 omitting the radiologic assessment for those patients at risk of MRONJ in presence dental/endo-periodontal diseases. #4 requiring generically radiologic exams without a specified diagnostic hypothesis. #5 prescribing radiological exams for MRONJ only after onset of jaws bone exposure. #6 diagnosing MRONJ only on the basis of the clinical signs, without radiologic assessment #7 prescribing high resolution imaging for soft tissue (with contrast medium) for diagnosis of MRONJ #8 planning MRONJ treatment without II level imaging exams for assessing the disease extension and severity #9 monitoring extension of MRONJ process only thanks to investigations of I Level (e.g. panoramic dental x-ray) Good practices #1 evaluate clinically and radiologically any local risk factors for MRONJ (i.e. dental/endo-periodontal diseases) for preventive dental screening in patients, remarkably neoplastic ones, who are candidates for therapies at risk of MRONJ. #2 reserve the indication for the execution of radiological exams of II (e.g. CT scan) to patients at risk only in the presence of ascertained clinical signs compatible with MRONJ. #3 perform radiological exams in all cases of dental/endo-periodontal diseases in patients at risk of MRONJ. #4 specify always the diagnostic hypothesis when prescribing radiological exams of any level (e.g. x-ray panoramic, CT, MR) in patients at MRONJ risk. #5 do not delay in prescribing radiologic exams to investigate signs of MRONJ, different from bone exposure. #6 integrate always the clinical check-up with the appropriate imaging exams for the diagnosis of MRONJ. #7 prescribe radiologic exams for bone diseases without contrast medium for diagnosis of MRONJ. #8 set up MRONJ treatment after defining its extension and severity also by targeted imaging. #9 use targeted imaging to monitor MRONJ during follow-up after conservative and/or surgical treatment.