Osteonecrosis of the jaw (ONJ) in patients with renal cancer treated with bisphosphonates (BPs) and sunitinib or other targeted therapy (TT) agents: A multicenter survey.

Fusco, Vittorio; Porta, Camillo; Paglino, Chiara; Bedogni, Alberto; Bettini, Giordana; Saia, Giorgia; Campisi, Giuseppina; Scoletta, Matteo; Agrillo, Alessandro; Fasciolo, Antonella

doi:10.1200/jco.2011.29.15_suppl.e15182

Cited by 4 publications

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“…There is also emerging evidence of an increased incidence of ONJ in cancer patients treated with tyrosine-kinase inhibitors and bevacizumab [76][77][78][79]. On the contrary, conflicting data have been published regarding the role of thalidomide [80,81]:…”

Section: Bronj In Metastatic Cancer and MM Patientsmentioning

confidence: 99%

Epidemiology, Clinical Manifestations, Risk Reduction and Treatment Strategies of Jaw Osteonecrosis in Cancer Patients Exposed to Antiresorptive Agents

et al. 2014

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Osteonecrosis of the jaws (ONJ) is an adverse side event of bisphosphonates and denosumab, antiresorptive agents that effectively reduce the incidence of skeletal-related events in patients with metastatic bone cancer and multiple myeloma. Available data suggest that 0-27.5% of individuals exposed to antiresorptive agents can develop ONJ. There is increasing evidence that avoidance of surgical trauma and infection to the jawbones can minimize the risk of ONJ, but there are still a significant number of individuals who develop ONJ in the absence of these risk factors. Bone necrosis is almost irreversible and there is no definitive cure for ONJ with the exclusion, in certain cases, of surgical resection. However, most ONJ individuals are affected by advanced incurable cancer and are often managed with minimally invasive nonsurgical interventions in order to control jawbone infections and painful symptoms. This article summarizes current knowledge of ONJ epidemiology, manifestations, risk-reduction and therapeutic strategies. Further research is needed in order to determine individual predisposition to ONJ and clarify the effectiveness of available treatments.

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Section: Bronj In Metastatic Cancer and MM Patientsmentioning

confidence: 99%

Epidemiology, Clinical Manifestations, Risk Reduction and Treatment Strategies of Jaw Osteonecrosis in Cancer Patients Exposed to Antiresorptive Agents

et al. 2014

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“…Several types of recent reports suggest a relatively high ONJ risk in RCC patients after a combination of bisphosphonates (mostly zoledronic acid) and antiangiogenic agents (mostly sunitinib) [9][10][11][12].…”

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confidence: 99%

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

Fusco

Bedogni

Campisi

2014

Support Care Cancer

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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][3][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 of denosumab in delaying or preventing skeletal-related events [1]. Amongst side effects, after a median (Q1, Q3) time on study of 6.7 (3.2, 13.0) and 6.4 (3.1, 12.9)months in the two groups, ONJ was reported in six denosumab arm patients (0.8 %) and in nine zoledronic acid arm patients (1.1 %).We wish to underline some sparse data reported in the cited papers, focusing attention on occurrence of ONJ in patients with renal cell cancer (RCC) included in the trial.In the summary ONJ analysis [5] of the above-mentioned three randomized trials comparing zoledronic acid and denosumab in patients with several cancer types and conducted between 2006 and 2009, it appears that an "Oral Event Identified as Potential ONJ" was registered in 276 patients out of 5,723 (4.8 %). Finally, cases of positively adjudicated ONJ according to very strict criteria were only 89 (1.6 %)-37 (1.3 %) on zoledronic acid and 52 (1.8 %) on denosumab. Notably, in the three trials, there were 14 ONJ cases among 464 patients treated with an antiresorptive agent (zoledronic acid or denosumab) and antiangiogenic agents (3.0 %) versus 75 ONJ cases among 5,259 patients receiving zoledronic acid or denosumab without any antiangiogenic agents (1.4 %) [5]: This kind of data seems to enforce recent literature data suggesting possible higher ONJ risk from combination of antiresorptive and antiangiogenic agents [7,8].According to the paper by Saad et al. [5], among 89 total adjudicated ONJ patients (treated either with zoledronic acid or denosumab) there were six RCC patients, out of a total number of enrolled RCC patients of 155 [1,4]. This 6/155 (3.9 %) ONJ frequency in RCC patients is more than twice as high, if compared with the entire patient population (1.6 %).In recent years, bone metastatic RCC patients received routinely targeted therapy, as monoclonal anti-VEGF antibody (bevacizumab), tyrosin-kinase inhibitors (sunitinib, sorafenib, pazopanib), mTOR inhibitors (temsirolimus, everolimus). Several types of recent reports suggest a relatively high ONJ risk in RCC patients after a combination of bisphosphonates (mostly zoledronic acid) and antiangiogenic agents (mostly sunitinib) [9][10][11][12].The question is: could the antiangiogenic treatment have played a role in the 3.9 % ONJ rate among RCC patients in the trial illustrated by Henry et al.? Unfortunately, a...

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“…The risk ratio for high-dose of intravenous medication versus low-dose oral administration was 14.6 (95% confidence interval 1.7-125.8) (Yamazaki et al, 2012). Studies also showed that the risk of MRONJ was greater when the anti-angiogenic drugs were combined with the BPs (Christodoulou et al, 2009;Fusco et al, 2015).…”

Section: Risk Factors For Mronjmentioning

confidence: 99%

“…MRONJ was more commonly observed in patients treated in combination between sunitinib and zolendronic acid rather than sunitib alone (Vallina et al, 2019), and MRONJ was more evident with zolendronic acid-sunitinib and not with zolendronic acid and sorafenib, pazopanib, temsirolimus or immunotherapy based on IL-2 (Smidt-Hansen et al, 2013;Ripamonti et al, 2016). This is because sunitinib is more potent against VEGFR and PDGF than the other drugs (Koch et al, 2011;Fusco et al, 2015). In addition, this drug can also cause gingival inflammation and mucositis, delayed wound healing and infection (Vallina et al, 2019).…”

Section: Theory Of Angiogenesis Inhibitionmentioning

confidence: 99%

MicroRNA in medication related osteonecrosis of the jaw: a review

et al. 2023

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Medication related osteonecrosis of the jaw (MRONJ) is a condition caused by inhibition of the osteoclast activity by the anti-resorptive and anti-angiogenic drugs. Clinically, there is an exposure of the necrotic bone or a fistula which fails to heal for more than 8 weeks. The adjacent soft tissue is inflamed and pus may be present as a result of the secondary infection. To date, there is no consistent biomarker that could aid in the diagnosis of the disease. The aim of this review was to explore the literature on the microRNAs (miRNAs) related to medication related osteonecrosis of the jaw, and to describe the role of each miRNA as a biomarker for diagnostic purpose and others. Its role in therapeutics was also searched. It was shown that miR-21, miR-23a, and miR-145 were significantly different in a study involving multiple myeloma patients as well as in a human-animal study while miR-23a-3p and miR-23b-3p were 12- to 14-fold upregulated compared to the control group in an animal study. The role of the microRNAs in these studies were for diagnostics, predictor of progress of MRONJ and pathogenesis. Apart from its potential diagnostics role, microRNAs have been shown to be bone resorption regulator through miR-21, miR-23a and miR-145 and this could be utilized therapeutically.

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Osteonecrosis of the jaw (ONJ) in patients with renal cancer treated with bisphosphonates (BPs) and sunitinib or other targeted therapy (TT) agents: A multicenter survey.

Cited by 4 publications

References 0 publications

Epidemiology, Clinical Manifestations, Risk Reduction and Treatment Strategies of Jaw Osteonecrosis in Cancer Patients Exposed to Antiresorptive Agents

Epidemiology, Clinical Manifestations, Risk Reduction and Treatment Strategies of Jaw Osteonecrosis in Cancer Patients Exposed to Antiresorptive Agents

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

MicroRNA in medication related osteonecrosis of the jaw: a review

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