Denosumab is commonly used to treat bone metastases in prostate cancer patients by inhibiting osteoclast activity and reducing bone resorption. However, one of the serious complications associated with its use is denosumab-related osteonecrosis of the jaw (DRONJ). While local oral risk factors have traditionally been considered primary contributors to DRONJ, recent research has increasingly focused on systemic risk factors, including body composition elements such as muscle mass and fat distribution. This study aims to investigate the clinical risk factors for DRONJ in prostate cancer patients with a focus on body composition.

We conducted a retrospective review of 64 prostate cancer patients with bone metastases who received denosumab between 2014 and 2023. Patient demographics, body composition (including sarcopenia defined by the previously reported total psoas muscle index cut-off value for Asians, visceral fat, subcutaneous fat, and BMI), and laboratory markers such as neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) were analyzed. The incidence of DRONJ and its associations with clinical factors were assessed.

Out of 64 patients, 12 (18.8%) developed DRONJ, with a mean onset time of 20.3 months. No significant associations were found between DRONJ and other factors, including age, initial PSA levels, Gleason score, visceral fat, subcutaneous fat, BMI, or histories of diabetes, hypertension, or smoking. The development of DRONJ did not affect cancer-specific survival or overall survival (log-rank test, p=0.77 and p=0.81, respectively). Sarcopenia was significantly associated with DRONJ development (P=0.033). Additionally, patients who developed DRONJ tended to have higher NLR and PLR values compared to those without the condition.

Sarcopenia has been reported to affect nutritional immune function and bone metabolism, and in prostate cancer patients, it may also play a role as a risk factor for DRONJ development. Our findings suggest that sarcopenia and low BMI are significant clinical risk factors, while inflammatory markers such as elevated NLR and PLR could further indicate increased risk. These results emphasize the importance of considering body composition and immune status in the management of prostate cancer patients receiving denosumab.