Paget’s disease of the bone (PDB) is a chronic bone disease which is characterized by accelerated bone turnover and disorganized bone remodeling. Diagnosis and treatment of PDB is particularly challenging in patients with chronic kidney disease (CKD). Denosumab administered subcutaneously at a single dose of 60 mg every 3 months reduced both serum total and bone-specific alkaline phosphatase (ALP) levels to near normal range in a 47-year-old male with CKD was suspected of having PDB due to very high serum total ALP levels and imaging findings suggestive of poliostotic involvement. Elevated serum total ALP levels detected at 3 months after denosumab suggests that serum total ALP starts to increase after 60 days of treatment but it is difficult to exactly determine the day when serum total ALP started to increase. It seems wise to administer denosumab at an interval of 60-120 days to maintain serum total ALP level within normal limits.