Denosumab‐related osteonecrosis of the jaw: A retrospective study

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Denosumab is a monoclonal antibody which has two commercial presentations in France: Prolia® (Amgen Inc, Thousand Oaks, CA, USA, for benign pathologies) and XGEVA® (Amgen Inc, for malignant diseases).
It acts by inhibiting the formation, function, and survival of osteoclasts to decrease bone resorption. For that, it targets the RANK/RANK‐L complex. It prevents the RANK activation by binding to the pre‐osteoclast RANK‐L and creates a saturation of osteoclast receptors.
Denosumab is indicated in cases of osteoporosis, Paget's disease (bone disease, localized and with slow progression), bone giant cell tumors, and bone metastases. It is a second‐line agent for Paget's disease if bisphosphonates are contraindicated. Denosumab is prescribed in almost the same indications as bisphosphonates and is gradually supplanting the latter because of its advantages. In fact, it is interesting to note that XGEVA® has a much shorter half‐life than bisphosphonates (28 days) and a shorter duration of action too (6 months vs 5‐10 years for bisphosphonates) while having a higher efficiency than zoledronic acid on bone metastases development.1
Nevertheless, Denosumab and bisphosphonates have common side effects such as hypocalcaemia, hypersensitivity to products (skin allergic reactions, hypotension, dyspnea, and angioedema) but also an atypical femur fracture or an osteonecrosis of the jaw.3
The American Association of Oral and Maxillofacial Surgeons described the medication‐related osteonecrosis of the jaw (MRONJ) as a mucosal lesion of the maxillofacial region with necrotic bone exposure (Figure 1).4 This exposure should be at least 8 weeks old and occur in patients receiving bisphosphonates or Denosumab. It must be in an area free of radiotherapy and bone metastases to be linked to medications. This definition describes both necroses related to the use of bisphosphonates and those related to the intake of Denosumab.
The management of MRONJ is mainly preventive with a dental consultation before prescription. During this consultation, it is important to explain to the patient the risk of necrosis and also to give him advice regarding dental hygiene. It is also important to have a regular dental follow‐up (4 times a year). In case of confirmed MRONJ, medication will be suspended in accordance with the prescribing physician. Despite all this, healing an osteonecrosis is long and sometimes complete cure can be obtained.6
Surgery is sometimes necessary to have a perfect eviction of all the necrotic bone area and/or to eliminate a bony sequestrum. Some more severe forms require the use of more invasive surgeries such as mandibulectomy. Finally, in case of infection of the necrotic area, the use of antibiotic is necessary and a regular monitoring will be established.7
Thus, Denosumab‐related osteonecrosis of the jaw (DRONJ) is a very delicate side effect of Denosumab. Indeed, the resolution of DRONJ is often long and complex. That is why the objectives of this study were to assess the occurrence rate of DRONJ at the Cancer Institute of Lorraine (Institut de Cancérologie de Lorraine, Vandoeuvre, ICL) and to highlight necrosis risk factors.
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