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Journal of Cancer Research and Therapeutics, Vol. 7, No. 4, October-December, 2011, pp. 499-500 Letter to the Editor - Documenting a Case Osteonecrosis of jaw with the use of denosumab Naveed Hassan Akhtar1, Muhammad Zubair Afzal2, Ali Arslan Aftab Ahmed1 1 Department of Hematology/Oncology, Weill Cornell Medical College, 525 East, 68th Street, New York-10065, USA Code Number: cr11133 DOI: 10.4103/0973-1482.92020 Sir, Osteonecrosis of jaw (ONJ) is described as the persistence of exposed bone in the oral cavity, even after an adequate treatment for eight weeks, without local evidence of malignancy and no prior radiotherapy. The use of bisphosphonates in patients with bone metastatic cancer to overcome the bone-related events has been associated with the occurrence of ONJ frequently. Denosumab is a fully human monoclonal antibody (mAb) of the IgG2 subtype, which targets the receptor activator of nuclear factor-κB (RANK) ligand. The use of this new compound is associated with a numerically higher number of ONJ cases compared with other drugs i.e. zoledronic acid. In three head-to-head prospective randomized controlled phase III studies in a broad variety of advanced cancer patients, 4 mg of zoledronate administered intravenously or 120 mg of denosumab injected subcutaneously were given monthly to 5677 patients for a mean of 12.1 (range 5.5-19.4) and 12.6 (range 5.6-19.4) months, respectively. 37 (1.3%) of those patients who were treated with zoledronate had ONJ as compared with 52 (1.8%) treated with denosumab. Notably, more patients on zoledronate (22%) were treated with antiangiogenic agents; a proposed risk factor for ONJ, than those on denosumab (12%), yet the number of patients who developed ONJ was higher in the denosumab group. [1] A meta-analysis of 10 randomized controlled trials involving 18,197 participants showed that the risk of serious infection was statistically significantly increased in patients treated with denosumab (P=0.04). [2],[3] This puts the patients on a much higher risk or getting osteomyelitis and increases their vulnerability to surgical infections whenever they undergo a procedure. Without doubt, several features make the oral cavity a unique environment .The alveolar bone in both the mandible and maxilla is covered by a layer of periosteum, epithelium, and connective tissue. These oral structures are subjected to a wide variety of stresses, (e.g., mastication), iatrogenic (e.g., dental procedures), or inflammatory (e.g., periodontal disease, caries) in nature. This combination of constant stress not only predisposes the thin mucosa to trauma, leading to exposure of bone, but also likely demands an increase in metabolic compensation including bone remodeling. As denosumab acts on RANKL receptor so it inhibits the osteoclasts, hence affecting the bone resorption in an adverse manner. Blockade of the RANK-RANKL interaction by a RANKL antibody such as denosumab affects monocyte migration, function and decreases the survival of these cells, a situation similar to that created by bisphosphonates. In the past, bisphosphonates, used extensively to prevent bone-related events in cancer patients, were responsible for causing ONJ. As of today, FDA has approved denosumab for non-metastatic prostate cancer and breast cancer patients on hormone deprivation therapy since it reduced the incidence of vertebral fracture. With an expected surge in the use of denosumab, development of ONJ should be monitored carefully in clinics. References
Copyright 2011 - Journal of Cancer Research and Therapeutics |
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