Incidence of medication-related osteonecrosis of the jaw in patients treated with both bone resorption inhibitors and vascular endothelial growth factor receptor tyrosine kinase inhibitors

Cann, Thomas Van; Loyson, Tine; Verbiest, Annelies; Clément, Paul M.; Bechter, Oliver; Willems, Ludo; Spriet, Isabel; Coropciuc, Ruxandra; Politis, Constantinus; Vandeweyer, Raf; Schoenaers, Joseph; Debruyne, Philip R.; Dumez, Herlinde; Berteloot, Patrick; Neven, Patrick; Nackaerts, Kristiaan; Woei-A-Jin, F J Sherida H; Punie, Kevin; Wildiers, Hans; Beuselinck, Benoît

doi:10.1007/s00520-017-3903-5

Cited by 47 publications

(40 citation statements)

References 16 publications

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“…Similarly, in our study, a significantly higher number of patients (92.8%), who developed MRONJ, had received BTAs for one or more year. Targeted therapies with concurrent BTAs were associated with earlier initiation and higher risk of MRONJ (Fung et al, ; van Cann et al, ). In line with those reports, targeted therapies were also significantly associated with increased MRONJ risk in the present study.…”

Section: Discussionmentioning

confidence: 99%

Alveolar bone histological necrosis observed prior to extractions in patients, who received bone‐targeting agents

et al. 2020

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Objective We reported the alveolar bone histology prior to dental extractions in cancer patients, who received bone‐targeting agents (BTA). Subjects and Methods Fifty‐four patients were included. Patients underwent extractions, and bone biopsies were taken. Results Extractions were performed due to pain, swelling, purulence, fistula, and numbness, not responding to treatment, in 40 patients (group A); extractions due to asymptomatic, non‐restorable teeth, were performed in 14 patients (group B). Complete alveolar jaw bone histological necrosis was observed in 28 of 40 (70%) patients of group A and none of group B (p < .001). The development of clinical osteonecrosis (MRON) was assessed in 44 patients; 10 patients, who were also treated with Low Level Laser Treatments‐LLLT, were excluded from this analysis, as the alternative therapies were a confounding factor. Twelve patients, with alveolar bone histological necrosis prior to extraction, developed medication‐related osteonecrosis of the jaw (MRONJ) compared with two patients with vital or mixed vital/non‐vital bone (p < .0007). BTAs >1 year and concurrent targeted therapy were also significantly associated with MRONJ (p = .016 and p = .050). Conclusion Pain, swelling, purulence, fistula, and numbness were significantly associated with complete bone histological necrosis prior to extractions and increased MRONJ development. Research is justified to explore whether histological necrosis represents an early stage of osteonecrosis.

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Section: Discussionmentioning

confidence: 99%

Alveolar bone histological necrosis observed prior to extractions in patients, who received bone‐targeting agents

et al. 2020

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“…22,24,26,29,59,120 In particular, the concomitant use of antiresorptives with agents that inhibit angiogenesis-that is, the formation of new blood vessels as part of tumor growth and spread-has been suggested to increase the likelihood of development of MRONJ, as recently reported in patients with advanced kidney cancer. 121 Incidence of medication-related osteonecrosis of the jaw with bisphosphonates or denosumab therapy The frequency of MRONJ is intrinsically linked to the cumulative exposure to, and potency of, the agent used to prevent SREs.…”

Section: Hypercalcemia Of Malignancymentioning

confidence: 99%

Medication-related osteonecrosis of the jaw: definition and best practice for prevention, diagnosis, and treatment

Nicolatou‐Galitis

Schiødt

Mendes

et al. 2019

Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology

250

203

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Skeletal complications caused by osteoporosis or bone metastases are associated with considerable pain, increased mortality, and reduced quality of life. Furthermore, such events place a burden on health care resources. Agents that prevent bone resorption, such as bisphosphonates or denosumab, can reduce the risk of skeletal-related events and are widely used in patients with osteoporosis or bone metastases of cancer. Medication-related osteonecrosis of the jaw (MRONJ) is a rare, but potentially serious, adverse event associated with high cumulative doses of bisphosphonates or denosumab. However, MRONJ can be treated, and the likelihood of the development of this condition can be reduced through prophylactic dental care and the maintenance of good oral hygiene. Dentists, as part of a multiprofessional team, have a critical role in preventing MRONJ. This review describes the incidence and pathophysiology of MRONJ and provides guidance for dental practitioners with regard to the screening, prophylactic treatment, diagnosis, and management of patients with this condition. (Oral Surg Oral Med Oral Pathol Oral Radiol 2019;127:117À135) Medication-related osteonecrosis of the jaw (MRONJ) is an uncommon condition that can occur after exposure to agents used to prevent bone complications, such as bisphosphonates or denosumab, or treatment with other agents, such as angiogenesis inhibitors. 1 In the majority of cases, MRONJ manifests as exposed bone in the maxillofacial region (Figure 1), although non-exposed MRONJ has also been recognized (Figure 2). 2-5 Bisphosphonates and denosumab are predominantly used to reduce the risk of skeletal complications in patients with bone loss, resulting from long-term cancer treatment or osteoporosis, and in patients with malignant bone disease. 6-8 Bisphosphonates are small molecules that dock in hydroxyapatite-binding sites on bone surfaces. When osteoclasts begin to resorb bisphosphonate-impregnated bone, the liberated bisphosphonates bind to farnesyl pyrophosphate synthase inside the osteoclasts, ultimately leading to apoptosis. 8-10 Denosumab is a fully human monoclonal antibody, which has a different mode of action from that of bisphosphonates. It targets and binds to the receptor activator of nuclear factor k-B (RANK) ligand (RANKL); in doing so it prevents the activation of RANK on the surface of osteoclasts and osteoclast precursors. Inhibition of the RANKLÀRANK interaction impedes osteoclast formation, function, and survival, thereby decreasing bone resorption. 11 MRONJ is more prevalent among patients receiving high cumulative doses of bisphosphonates or denosumab than in patients who receive lower doses. 12,13 The first cases Statement of Clinical Relevance Medication-related osteonecrosis of the jaw is a rare, but potentially serious, complication of treatment with bisphosphonates and denosumab. It is important for dentists to be aware of ways to identify and treat patients at risk of this condition.

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“…Several case reports described high risk association with zoledronic acid and sunitinib678. Recently, a global MRONJ-incidence of 11% in patients receiving concomitant treatment with VEGFR-TKIs and bone resorption inhibitors has been reported9 and the risk is very high if BPs were previously administered. The risk of transformation of induced chemotherapy oral mucositis to bisphosphate-related ONJ (BRONJ) has been described.…”

Section: Tyrosine Kinase Inhibitors (Tkis)mentioning

confidence: 99%

Osteonecrosis of the jaw in the era of targeted therapy and immunotherapy in oncology

Nifosì

Zuccarello

Lorenzo

et al. 2019

J Korean Assoc Oral Maxillofac Surg

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Osteonecrosis of the jaw (ONJ) is a well-known pathological condition in oncology derived from the use of bisphosphonates (BPs) and denosumab. Many molecular and immunological targets have been introduced for daily use in cancer treatment in recent years; consequently, new cases of ONJ have been reported in association with these drugs, especially if administered with BPs and denosumab. When the drugs are administered alone, ONJ is rarely seen. The objective of our study was to analyze the recent literature relative to the association of ONJ with these new drugs highlighting the pathogenic, clinical and therapeutic aspects. The close collaboration between maxillofacial surgeon, oncologist, dentist, and dental hygienist remains the most important aspect for the prevention, prompt recognition, and treatment of this pathology.

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Incidence of medication-related osteonecrosis of the jaw in patients treated with both bone resorption inhibitors and vascular endothelial growth factor receptor tyrosine kinase inhibitors

Abstract: With a global MRONJ-incidence of 11%, patients receiving concomitant treatment with VEGFR-TKIs and BRIs have a five to ten times higher risk for development of MRONJ compared to patients treated with BRIs alone.

Cited by 47 publications

References 16 publications

Alveolar bone histological necrosis observed prior to extractions in patients, who received bone‐targeting agents

Alveolar bone histological necrosis observed prior to extractions in patients, who received bone‐targeting agents

Medication-related osteonecrosis of the jaw: definition and best practice for prevention, diagnosis, and treatment

Osteonecrosis of the jaw in the era of targeted therapy and immunotherapy in oncology

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