Osteonecrosis of the jaw (ONJ) is a common and potentially severe complication of antiresorptive therapy for bone metastases. However, its occurrence in patients treated for osteoporosis is rare. Although poor oral hygiene and invasive dental procedures have been identified as potential triggers, little is known about the role of other systemic risk factors. We describe a patient who developed ONJ after her first treatment with denosumab, a monoclonal antibody against receptor activator of NF-kB ligand. This patient had several comorbidities that prompted us to assess the German ONJ registry for the incidence of comorbidities in patients with ONJ. In summary, almost half of the patients (35 of 86 [41%]) had 1 or more risk factors thought to increase the risk of ONJ. In conclusion, comorbidities or comedications may increase the susceptibility of developing ONJ during osteoporosis therapy.