A pragmatic window of opportunity to minimise the risk of MRONJ development in individuals with osteoporosis on Denosumab therapy: a hypothesis

Abstract Denosumab is associated with the development of medication-related osteonecrosis of the jaw (MRONJ), an uncommon but severe oral side effect with a higher prevalence in metastatic cancer patients than in patients with metabolic bone fragility. Although several oral triggers can initiate MRONJ, invasive oral treatments and tooth extraction still remain the most common precipitating event. In general, tooth extraction and oral surgery should be avoided in patients at increased risk of MRONJ, while extraction of non-restorable teeth should be performed based on specific risk reduction protocols to eliminate dental/periodontal infections, still protecting from MRONJ onset. Based on th…

Comment on Medication-Related Osteonecrosis of the Jaw: MASCC/ISOO/ASCO Clinical Practice Guideline Summary

Comments on “Diagnosis and Management of Osteonecrosis of the Jaw: A Systematic Review and International Consensus”

Simplifying the dental/periodontal management of patients with metabolic bone fragility receiving treatment with denosumab

Denosumab (DNB) is a bone-targeted medication used to preserve structural integrity and minimise the risk of fragility fractures in metastatic cancer and metabolic bone disorders. DNB targets and binds RANK Ligand, inhibiting osteoclast maturation, function, and survival. In contrast with nitrogen-containing bisphosphonates (N-BPs), DNB does not bind to hydroxyapatite and incorporate into bone; thus, bone cellular remodelling recovers rapidly after drug suspension. Denosumab has benn linked to the occurrence of osteonecrosis of the jaw (MRONJ), a uncommon but severe oral side effect with a higher prevalence in metastatic cancer patients than in patients with metabolic bone fragility. Althou…

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 III

Osteonecrosi dei mascellari associata a bisfosfonati, denosumab e farmaci anti-angiogenetici nei pazienti oncologici e osteoporotici: diagnosi e terapia

Riassunto Obiettivi Fornire un percorso utile alla diagnosi e al trattamento dell’osteonecrosi delle ossa mascellari (solitamente definita ONJ, OsteoNecrosis of the Jaws). Materiali e metodi Gli autori del lavoro, recentemente estensori e collaboratori – su mandato della Societa Italiana di Chirurgia Maxillo-Facciale (SICMF) e della Societa Italiana di Patologia e Medicina Orale (SIPMO), delle Raccomandazioni clinico-terapeutiche sull’osteonecrosi delle ossa mascellari associata a bisfosfonati e sua prevenzione – hanno esaminato le informazioni scientifiche disponibili in merito alla ONJ associata all’assunzione sia di bisfosfonati sia di denosumab e/o anti-angiogenetici, e revisionato l’ep…

Review of: "Teriparatide Promotes Bone Healing in Medication-Related Osteonecrosis of the Jaw: A Placebo-Controlled, Randomized Trial"

Learning from experience. Proposal of a refined definition and staging system for bisphosphonate-related osteonecrosis of the jaw (BRONJ)

Dear Editor, It is the authors’ belief that the internationally accepted definition of bisphosphonate-related osteonecrosis of the jaws (BRONJ) (Ruggiero et al, 2009) has several limitations that prevent clinicians from being confident with the diagnosis of the disease. Following recognition of the non-exposed BRONJ clinical variant (Lazarovici et al, 2009), we all became aware that the presence of ‘exposed necrotic bone in the oral cavity’, as outlined in the American Association of Oral and Maxillofacial Surgery (AAOMS) case definition, is just one of the possible clinical manifestations of BRONJ and is not found in all BRONJ patients. As ‘bone exposure’ is certainly not the initial sign …

The Treatment of Medication-Related Osteonecrosis of the Jaw (MRONJ): A Systematic Review with a Pooled Analysis of Only Surgery versus Combined Protocols

Medication-related osteonecrosis of the jaw (MRONJ) is a serious adverse reaction of antiresorptive and antiangiogenic agents, and it is also a potentially painful and debilitating condition. To date, no specific studies have prospectively evaluated the efficacy of its treatment and no robust standard of care has been established. Therefore, a systematic review (2007–2020) with a pooled analysis was performed in order to compare MRONJ surgical techniques (conservative or aggressive) versus combined surgical procedures (surgery plus a non-invasive procedure), where 1137 patients were included in the pooled analysis. A statistically significant difference in the 6-month improvement rate, comp…

RE: MEDICATION-RELATED OSTEONECROSIS OF THE JAW (MRONJ)

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.

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).

The preventive care of medication-related osteonecrosis of the jaw (MRONJ): a position paper by Italian experts for dental hygienists

Abstract Purpose The prevention and early diagnosis of medication-related osteonecrosis of the jaw (MRONJ) is fundamental to reducing the incidence and progression of MRONJ. Many in the field believe that dental hygienists should play an integral role in primary and secondary MRONJ prevention. However, to date, very few publications in the literature have proposed standardised MRONJ protocols, which are dedicated to dental hygienists. The aim of this study was to provide guidance to the health care providers managing MRONJ. Methods The expert opinion in this study was developed by dental hygienists from the main Italian technical-scientific associations (Italian Dental Hygienists Associatio…

Medication-Related Osteonecrosis of Jaws (MRONJ) Prevention and Diagnosis: Italian Consensus Update 2020

The Medication-Related Osteonecrosis of Jaws (MRONJ) diagnosis process and its prevention play a role of great and rising importance, not only on the Quality of Life (QoL) of patients, but also on the decision-making process by the majority of dentists and oral surgeons involved in MRONJ prevention (primary and secondary). The present paper reports the update of the conclusions from the Consensus Conference—held at the Symposium of the Italian Society of Oral Pathology and Medicine (SIPMO) (20 October 2018, Ancona, Italy)—after the newest recommendations (2020) on MRONJ were published by two scientific societies (Italian Societies of Maxillofacial Surgery and Oral Pathology and Medicine, SI…

Staging of osteonecrosis of the jaw requires computed tomography for accurate definition of the extent of bony disease

AbstractManagement of osteonecrosis of the jaw associated with antiresorptive agents is challenging, and outcomes are unpredictable. The severity of disease is the main guide to management, and can help to predict prognosis. Most available staging systems for osteonecrosis, including the widely-used American Association of Oral and Maxillofacial Surgeons (AAOMS) system, classify severity on the basis of clinical and radiographic findings. However, clinical inspection and radiography are limited in their ability to identify the extent of necrotic bone disease compared with computed tomography (CT). We have organised a large multicentre retrospective study (known as MISSION) to investigate th…

Adjuvant denosumab in early breast-cancer

We read with interest the D-CARE trial report by Robert Coleman and colleagues1 on the adjuvant administration of denosumab in patients with early-stage breast cancer. Despite the negative results, which pose concerns about high dose denosumab schedules in an adjuvant setting, this large and well- designed trial can provide useful clinical data that are usually difficult to obtain from observational studies, particularly regarding medication- related osteonecrosis of the jaw (MRONJ).

One changing and challenging scenario: the treatment of cancer patients with bone metastases by bisphosphonates and denosumab, the cost-benefit evaluation of different options, and the risk of medication-related osteonecrosis of the jaw (MRONJ)

Antiresorptive drugs (bisphosphonates and denosumab) have become the cornerstone of medical supportive treatment of bone metastases in solid cancer patients. In the beginning, the choice of available antiresorptive agents was limited to bisphosphonates and the treatment options restricted principally to monthly pamidronate and monthly zoledronic acid. Introduction of new antiresorptive therapies (monthly denosumab) and schedules (zoledronic acid every 3 months, upfront or after initial period of monthly infusion) in the last decade increased the range of available options, thus challenging treatment decision making. Direct and indirect costs of very different treatment options are difficult…

RE: Regorafenib Also Can Cause Osteonecrosis of the Jaw

BRONJ in patients with rheumatoid arthritis: A multicenter case series

Objective: Osteonecrosis of the jaw (ONJ) is a potentially severe adverse effect of various medications (bisphosphonates, anti-resorptive, and anti-angiogenic drugs). ONJ pathogenesis is still unclear although some risk factors have been recognized. Of these, rheumatoid arthritis (RA) has been hypothesized as a potential risk factor for developing ONJ. This observational study will describe a multicenter case series of patients affected with RA and ONJ, and it will attempt to evaluate the association between features of ONJ and pharmacological, systemic, and site variables. Methods: Demographic, pharmacological, and clinical data from 18 RA patients with ONJ were collected and registered fr…

Osteonecrosis of the Jaw in Myeloma Patients Receiving Denosumab or Zoledronic Acid. A Commentary of the Pivotal Trial by Raje et al. Published on Lancet Oncology.

The recent randomized trial, published by Raje et al., on Lancet Oncology is potentially practice changing. It proposes that denosumab is a valid alternative to zoledronic acid in the treatment of myeloma patients. However, several points need further data and more details, such as information on incidence, diagnosis, and follow-up of osteonecrosis of the jaw (ONJ) cases, observed among treated patients. Adopted definition to adjudicate ONJ cases, type of registration of potential ONJ cases, length of observation are possible causes of potential underestimation of ONJ incidence in their study. Future updated evaluations with longer follow-up, and including actuarial estimation, are required…

MRONJ in breast cancer patients under bone modifying agents for cancer treatment-induced bone loss (CTIBL): a multi-hospital-based case series

Abstract Background Cancer treatment-induced bone loss (CTIBL) is the most common adverse event experienced by patients affected by breast cancer (BC) patients, without bone metastases. Bone modifying agents (BMAs) therapy is prescribed for the prevention of CTIBL, but it exposes patients to the risk of MRONJ. Methods This multicentre hospital-based retrospective study included consecutive non-metastatic BC patients affected by MRONJ related to exposure to low-dose BMAs for CTIBL prevention. Patients’ data were retrospectively collected from the clinical charts of seven recruiting Italian centres. Results MRONJ lesions were found in fifteen females (mean age 67.5 years), mainly in the mandi…

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 II

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)

Osteonecrosis of the Jaw in Patients With Metastatic Renal Cell Cancer Treated With Bisphosphonates and Targeted Agents: Results of an Italian Multicenter Study and Review of the Literature.

Osteonecrosis of the jaw (ONJ) associated with the use of bisphosphonates has been rarely reported in metastatic renal cell cancer (RCC) patients. Since the introduction of combined therapies consisting of nitrogen-containing bisphosphonates (NBPs) and targeted agents, an increasing number of RCC patients were reported to develop ONJ, suggesting that therapeutic angiogenesis suppression might increase the risk of ONJ in NBPs users. We performed a multicenter retrospective study and reviewed literature data to assess the occurrence and to investigate the nature of ONJ in RCC patients taking NBPs and targeted agents. Nine Italian Centers contributed to the data collection. Patients with expos…

The dental management of patients at risk of medication-related osteonecrosis of the jaw: New paradigm of primary prevention

Medication-related osteonecrosis of the jaw (MRONJ) is a serious adverse reaction of antiresorptive and antiangiogenic agents; it is a potentially painful and debilitating condition that can considerably affect the quality of life of patients. Furthermore, even if its epidemiology and pathogenesis have still not been fully clarified, several risk factors related to MRONJ have been recognized in prevention protocols. Three main risk factors are as follows: (i) the type of ONJ-related medications: antiresorptive (e.g., Bisphosphonates, Denosumab) and antiangiogenic drugs (e.g., Bevacizumab, Sunitinib); (ii) the category of patient at MRONJ risk: cancer versus non-cancer patient; (iii) the typ…

Medication related osteonecrosis of the jaw (MRONJ)

Definition and estimation of osteonecrosis of jaw (ONJ), and optimal duration of antiresorptive treatment in bone metastatic cancer patients: supplementary data from the denosumab extension study?

To the Editor, In their recent article, Stopeck et al. [1] concluded that denosumab confirms its known safety profile even after longterm exposure, or after switching to it from zoledronic acid, and that osteonecrosis of jaws (ONJ) rates increased with increasing exposure to antiresorptives, consistent with previous reports. This is based on the open label extension phase of two phase 3 studies in patients with breast and prostate cancer with bone metastases who were randomized to receive denosumab or zoledronic acid (ZA) [2, 3]. The patients were offered open-label denosumab for up to an additional 2 years after the results of the primary analysis, favorable for denosumab on several aspect…

Up to a quarter of patients with osteonecrosis of the jaw associated with antiresorptive agents remain undiagnosed

AbstractRecent data suggest that the traditional definition of bisphosphonate-associated osteonecrosis of the jaw (ONJ) may exclude patients who present with the non-exposed variant of the condition. To test the hypothesis that a proportion of patients with ONJ remain undiagnosed because their symptoms do not conform to the traditional case definition, we did a secondary analysis of data from MISSION (Multicentre study on phenotype, definition and classification of osteonecrosis of the jaws associated with bisphosphonates), a cross-sectional study of a large population of patients with bisphosphonate-associated ONJ who were recruited in 13 European centres. Patients with exposed and non-exp…

Osteonecrosis of the jaw (ONJ) in renal cell cancer patients after treatment including zoledronic acid or denosumab.

Dear Editor, The paper by Henry et al. published by Supportive Care in Cancer comparing efficacy of denosumab versus zoledronic acid in patients with bone metastases of advanced solid tumours [1] comes to integrate the original reports of three pivotal large randomized phase 3 trials [2–4], the publication by Saad et al. about osteonecrosis of the jaw (ONJ) in those three trials [5], and the combined outcome analysis by Lipton et al. [6]. Henry et al. [1] reported outcomes of the single trial conducted on patients with solid tumours (except breast or prostate cancers, object of other two trials) [2, 3], excluding patients with multiple myeloma: This ad hoc analysis confirmed the superiority…

Osteonecrosi dei mascellari associata a bisfosfonati, denosumab e farmaci anti-angiogenetici nei pazienti oncologici e osteoporotici: prevenzione dentale e sicurezza dei trattamenti odontoiatrici

Riassunto Obiettivi Proporre protocolli di gestione odontoiatrica per il paziente che assume o che assumera farmaci (per esempio bisfosfonati, denosumab e anti-angiogenetici) correlati all’insorgenza di osteonecrosi dei mascellari (OsteoNecrosis of the Jaws, ONJ). Materiali e metodi Gli autori del lavoro, recentemente estensori e collaboratori – su mandato della Societa Italiana di Chirurgia Maxillo-Facciale (SICMF) e della Societa Italiana di Patologia e Medicina Orale (SIPMO), delle Raccomandazioni clinicoterapeutiche sull’osteonecrosi delle ossa mascellari associata a bisfosfonati e sua prevenzione – hanno esaminato le informazioni scientifiche disponibili in merito alla ONJ (associata a…

Comment on “Medication-Related Osteonecrosis of the Jaw (MRONJ)” by Elie M. Ferneini in the Section “Simply Put: JOMS Information for Patients”

We read with great interest the contribute to the section “Simply Put: JOMS Information for Patients” named “Medication-Related Osteonecrosis of the Jaw (MRONJ)” by Elie M. Ferneini.

Conservative Surgical Treatment of Bisphosphonate-Related Osteonecrosis of the Jaw with Er,Cr:YSGG Laser and Platelet-Rich Plasma: A Longitudinal Study

Introduction. The management of bisphosphonate-related osteonecrosis of the jaw (BRONJ), with no evidence-based guidelines, remains controversial. We aimed to evaluate the efficiency of a conservative surgical treatment combining Er,Cr:YSGG laser and platelet-rich plasma (PRP) for the treatment of BRONJ in cancer patients. Methods. We performed a longitudinal cohort study. Inclusion criteria were (1) age ≥ 18 years; (2) cancer diagnosis; (3) treatment with NBP because of the underlying cancer. Results. We consecutively recruited ten patients diagnosed with BRONJ in stage I or II. These patients underwent a surgical laser-assisted therapy together with autologous PRP. At the latest follow-up…