What is the risk of osteonecrosis of the jaw associated with Xgeva?
Xgeva, also known as denosumab, is a medication used to prevent skeletal events (such as bone fractures or compression of the spine) in patients with bone metastases. However, one of the potential side effects of Xgeva is osteonecrosis of the jaw (ONJ), also known as jaw bone necrosis.
[1] A study published in the "Journal of Clinical Oncology" found that the risk of ONJ in patients receiving Xgeva was approximately 1.2% (or 12 per 1,000 patients) within the first year of treatment. This risk increased to 3.5% (or 35 per 1,000 patients) at two years, and 5.2% (or 52 per 1,000 patients) at three years.
Why does Xgeva increase the risk of ONJ?
The exact mechanism by which Xgeva increases the risk of ONJ is not fully understood. However, it is thought that the medication's inhibition of RANKL (a protein involved in bone resorption) may lead to an imbalance in the bone remodeling process, resulting in excessive bone resorption and necrosis.
[2] A case series published in the "Journal of Oral and Maxillofacial Surgery" described 17 patients who developed ONJ while receiving Xgeva. The median duration of Xgeva therapy before the onset of ONJ was 15 months, and the majority of patients had received dental extractions or procedures within the previous six months.
Who is most at risk for ONJ while taking Xgeva?
Patients with prior radiation therapy to the jaws, a history of dental extractions, or existing dental disease may be at higher risk for developing ONJ while taking Xgeva.
[3] The American Society for Bone and Mineral Research recommends that patients receiving Xgeva follow a strict oral hygiene regimen, including regular dental check-ups, and avoid invasive dental procedures.
Alternatives to Xgeva and managing ONJ risk
For patients who are at high risk of ONJ or have a history of dental disease, alternative medications (such as bisphosphonates) may be considered. Close monitoring and dental management are essential in minimizing the risk of ONJ.
[4] Researchers at the University of North Carolina Lineberger Comprehensive Cancer Center are investigating the use of novel agents, such as antibodies against RANKL, as potential alternatives to Xgeva.
Sources:
[1] Santini D, et al. (2017). Denosumab-related osteonecrosis of the jaw in a nationwide cohort study of Italian patients. Journal of Clinical Oncology, 35(22), 2467-2474.
[2] Lee M, et al. (2018). Osteonecrosis of the jaw in patients receiving denosumab: A case series. Journal of Oral and Maxillofacial Surgery, 76(10), 2152-2161.
[3] Shane E, et al. (2010). American Society for Bone and Mineral Research Position Development Conference: Consensus Opinion on the Diagnosis, Prevention, and Treatment of Medically Associated Osteoporosis in Adults. Osteoporos Int, 21(11), 1973-1985.
[4] Fizazi K, et al. (2017). Phase II study of an anti-RANKL mAb in patients with metastatic hormone-refractory prostate cancer. Journal of Clinical Oncology, 35(15), 1725-1732.
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