Chronic kidney disease (CKD) is associated with bone and mineral disturbances in the form of renal osteodystrophy. The American College of Rheumatology Guidelines for the Prevention and Treatment of Glucocorticoid-Induced Osteoporosis 2017 recommend against treatment with denosumab in adult patients who have received an organ transplant and who are continuing treatment with glucocorticoids due to lack of adequate safety data on infections in adults treated with multiple immunosuppressive agents. Therefore, this study was conducted to compare the safety of denosumab in patients with CKD, especially in a group of patients who received immunosuppressive medications, and to assess the rate of infections in such group in comparison to patients with normal renal function. We retrieved all data of patients who are receiving denosumab in our institute through search in the medical record system (Al-Shifa System). We excluded all patients with malignancy and all patients who were prescribed denosumab but did not receive it. During the period from 2006 to 2018, 314 patients were treated with denosumab therapy. Out of 84 patients who were fulfilling the inclusion criteria, 24 (28.5%) patients had normal kidney function and 60 (71.4%) patients had CKD. Forty-three percent of all patients with CKD developed side effects after taking denosumab. In comparison, only 17% of patients with normal kidney function developed side effects. Of patients with CKD and infections, 50% of them had moderate infections and required admission. Out of these patients, 76% were in immunosuppressive medications and 61% of the patients were receiving steroids more than 2.5 mg per day. Using Chi-square test and the nonparametric independent samples Kruskal-Wallis test, there was a significant association between the dose of steroids and the rate of side effects with a significance level of <0.014 and 0.009, respectively. Hypocalcemia was detected in two patients (3.3%), and they had CKD stage V. Denosumab is associated with increased risk of infection in CKD patients on steroids or multiple immuno-suppressive medications. There was no deterioration in renal function while using denosumab. In this regard, close monitoring of this group of patients is essential, as well as medication adjustments.