Denosumab-associated osteonecrosis of the jaw – a case report

Vyas, Sheena; Hameed, Sabina; Murugaraj, V.

doi:10.12968/denu.2014.41.5.449

Cited by 13 publications

(5 citation statements)

References 6 publications

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“…Since the first description by Taylor et al . 18 detailed cases of DRONJ have been reported in the English‐language literature (Table ) . Additional studies have focused on DRONJ, but detailed description of dosing and length of treatment, etiologic factors, and specific treatment protocols were not always provided .…”

Section: Discussionmentioning

confidence: 99%

Denosumab‐related osteonecrosis of the jaws: successful management with a conservative surgical approach

Póvoa

Marlière

Silveira

et al. 2016

Special Care in Dentistry

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Denosumab‐related osteonecrosis of the jaws (DRONJ) is a recently described entity that shares many common clinical and radiological features with bisphosphonate‐related osteonecrosis of the jaws (BRONJ). The aim of the present study is to report a case of DRONJ affecting the anterior mandible of a 58‐year‐old male treated with denosumab to prevent skeletal‐related events associated with prostate cancer. Conservative surgery in conjunction with antibiotic therapy and discontinuation of denosumab use were effective in managing the condition and the patient remains free of clinical and radiological changes after a 38 month follow‐up.

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Section: Discussionmentioning

confidence: 99%

Denosumab‐related osteonecrosis of the jaws: successful management with a conservative surgical approach

Póvoa

Marlière

Silveira

et al. 2016

Special Care in Dentistry

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“…Recent therapeutic strategies for treating bone metastasis include surgery, radiotherapy and osteoclast inhibitors, such as bisphosphonates and denosumab, the human monoclonal antibody used to neutralize RANKL. Regardless of the wide use of these treatments, radiotherapy should still be administered for symptom palliation (57), although bisphosphonates and denosumab can cause unfavorable side-effects, such as osteonecrosis of the jaw (11)(12)(13)(14). Based on these findings, new strategies for the treatment of bone metastases with fewer side-effects are required.…”

Section: Discussionmentioning

confidence: 99%

“…However, the effects of these treatment modalities remain limited. In addition, osteonecrosis of the jaw and hypocalcemia represent serious side-effects and long-term prognosis associated with these treatments remains unknown (11)(12)(13)(14).…”

Section: Transcutaneous Carbon Dioxide Application Suppresses Bone Dementioning

confidence: 99%

Transcutaneous carbon dioxide application suppresses bone destruction caused by breast cancer metastasis

et al. 2018

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Hypoxia plays a significant role in cancer progression, including metastatic bone tumors. We previously reported that transcutaneous carbon dioxide (CO2) application could decrease tumor progression through the improvement of intratumor hypoxia. Therefore, we hypothesized that decreased hypoxia using transcutaneous CO2 could suppress progressive bone destruction in cancer metastasis. In the present study, we examined the effects of transcutaneous CO2 application on metastatic bone destruction using an animal model. The human breast cancer cell line MDA-MB-231 was cultured in vitro under three different oxygen conditions, and the effect of altered oxygen conditions on the expression of osteoclast-differentiation and osteolytic factors was assessed. An in vivo bone metastatic model of human breast cancer was created by intramedullary implantation of MDA-MB-231 cells into the tibia of nude mice, and treatment with 100% CO2 or a control was performed twice weekly for two weeks. Bone volume of the treated tibia was evaluated by micro-computed tomography (µCT), and following treatment, histological evaluation was performed by hematoxylin and eosin staining and immunohistochemical staining for hypoxia-inducible factor (HIF)-1α, osteoclast-differentiation and osteolytic factors, and tartrate-resistant acid phosphatase (TRAP) staining for osteoclast activity. In vitro experiments revealed that the mRNA expression of RANKL, PTHrP and IL-8 was significantly increased under hypoxic conditions and was subsequently reduced by reoxygenation. In vivo results by µCT revealed that bone destruction was suppressed by transcutaneous CO2, and that the expression of osteoclast-differentiation and osteolytic factors, as well as HIF-1α, was decreased in CO2-treated tumor tissues. In addition, multinucleated TRAP-positive osteoclasts were significantly decreased in CO2-treated tumor tissues. Hypoxic conditions promoted bone destruction in breast cancer metastasis, and reversal of hypoxia by transcutaneous CO2 application significantly inhibited metastatic bone destruction along with decreased osteoclast activity. The findings in this study strongly indicated that transcutaneous CO2 application could be a novel therapeutic strategy for treating metastatic bone destruction.

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“…By contrast, Diz et al (12) reported a case of denosumab-related ONJ due to tooth extraction 6 months after cessation of denosumab therapy. Notably, Vyas et al (38) reported a case of denosumab-related ONJ that healed within 1 month of cessation of denosumab. Thus, it is difficult to determine the appropriate period of a drug holiday for denosumab.…”

Section: Discussionmentioning

confidence: 99%

Denosumab-related osteonecrosis of the jaw in a patient with bone metastases of prostate cancer: A case report and literature review

et al. 2017

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Denosumab, a human monoclonal antibody directed against the receptor activator of nuclear factor-κβ ligand (RANKL), is used for the treatment of patients with metastatic cancer of the bone or osteoporosis. Recent reports have demonstrated that denosumab can induce osteonecrosis of the jaw (ONJ), but reported cases of this are uncommon. The present study reports the case of an 86-year-old male with prostate cancer patient exhibiting bone metastases who developed ONJ whilst receiving denosumab. To elucidate the influence of denosumab on the development of ONJ, the present study also reviewed the literature, including clinical trials and case reports. In the clinical trials, the prevalence of denosumab-related ONJ was higher in patients with cancer compared with those with osteoporosis. The high risk of ONJ in patients with cancer was thought to be associated with the differing dose and frequency of denosumab administration. The prevalence of ONJ was not significantly different between patients receiving denosumab and bisphoshonate (BP). In the reported cases, denosumab-related ONJ had a similar clinical presentation to BP-related ONJ. There was also a tendency for denosumab-related ONJ to develop in the mandible of elderly patients. Previous invasive dental treatment was a commonly shared characteristic of patients with denosumab-related ONJ. A complex medical history was also suspected to affect the prevalence. No clear association between the dose or duration of denosumab treatment and the development of ONJ was observed. Although conservative treatments are given for denosumab-related ONJ, non-improving cases were managed surgically with primarily positive results. Because denosumab may offer superior results compared with BP for the treatment of metastatic cancer of the bone or osteoporosis, the use of denosumab is expected to increase in the near future. Clinicians should also be aware of the risk factors for denosumab-related ONJ, in order to aid in its diagnosis. In addition, patients treated with denosumab should receive prophylactic treatment to maintain their oral health prior to, during and after denosumab treatment.

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Denosumab-associated osteonecrosis of the jaw – a case report

Cited by 13 publications

References 6 publications

Denosumab‐related osteonecrosis of the jaws: successful management with a conservative surgical approach

Denosumab‐related osteonecrosis of the jaws: successful management with a conservative surgical approach

Transcutaneous carbon dioxide application suppresses bone destruction caused by breast cancer metastasis

Denosumab-related osteonecrosis of the jaw in a patient with bone metastases of prostate cancer: A case report and literature review

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