Chronic rhinosinusitis associated with nasal polyposis (RSCwNP) affects 4% of the general population. As chronic condition, it requires chronic pharmacological treatment, whereas the surgical approach becomes necessary in obstructive and/or complicated cases. Intranasal and systemic corticosteroids (CS) represent the ''Gold Standard'' treatment for RSCwNP. The present study aimed to evaluate the side effects of prednisone in a group of patients with RSCwNP treated with long-term CS. In particular, attention was focused on bone disorders (osteopenia and osteoporosis) and prospective fracture risk increase. Forty patients (26 females, mean age 55.70 ± 14.03 years) affected by RSCwNP have been enrolled. Control group included 40 healthy subjects (17 females, mean age 56.37 ± 13.03 years). Nasal endoscopy, skin prick tests, nasal cytology, and bone densitometry were evaluated in all subjects. The likelihood of impaired bone metabolism (osteopenia or osteoporosis) was superimposable in both groups. Within RSCwNP group, no parameter was statistically significant in predicting a metabolism alteration.