Safety & Efficacy of Denosumab in Chronic Kidney Disease Patients in Dubai Hospital: Single Center Experience

Abstract

Chronic kidney disease (CKD) patients has not only higher risk of bone fractures due to low bone mineral density & poor bone quality, but also carries high risk of cardiovascular disease due to soft tissue calcification in conjunction with secondary hyperparathyroidism and high phosphate. Bisphosphonates use was limited in CKD patients due to nephrotoxicity while Denosumab were found safe & effective. Purpose of study was to report efficacy & safety of denosumab in different stages of CKD, also to compare it with normal renal function patients. With help of medical software, data was collected for patients who received denosumab for osteoporosis, osteopenia or fragile fractures at least for 6 months. 90 patients were included (Osteoporosis 53.34%, fractures 25.56% & osteopenia 21.11%), 80% had CKD (Stage III: n=32,44.44%, Stage V: n=23, 31.94% & Stage IV n=11, 15.27%) while 20% had normal renal functions (NKF). CKD patients belonged to older age group than NKF patients (79±13 vs 73.06±13.63, p=<0.05). Osteoporosis (CKD vs NKF: 47.22% vs 77.78%, p<0.05) & Osteopenia (CKD vs NKF: 20.83% vs 22.22%, p >0.05) were more common in NKF patients, while fractures were more common in CKD patients (CKD vs NKF: 29.16% vs 11.11% p=>0.05). After denosumab therapy, there was not much improvement in osteopenia (pre & post in CKD: 20.83% vs 19.45%, p >0.05) or osteoporosis (pre & post 47.22% vs 45.80% p= >0.05) in CKD patients, while fracture frequency increased (pre & post in CKD:  29.16% vs 34.70%, p=>0.05) however these findings were not statistically significant. After Denosumab therapy, there was significant drop in median (IQR) corrected serum calcium {pre & post: 9.4(0.68) vs 9.2 (0.72), p<0.05}, while increase in parathyroid hormone {PTH pre & post: 46.5(74.77) vs 68.25(157.17), p<0.05) & 25 hydroxy vitamin D {pre & post denosumab: 28.50(17.65) vs 37.45(25.12), p<0.05} in CKD patients, whereas there was no significant change in phosphate. Positive effects of denosumab on BMD were not appreciated in our CKD population. Hypocalcemia is significant side effect and can be dealt with close monitoring, aggressive diet to provide calcium & vitamin D, awareness of doctors & health care professionals to set up integrated multidisciplinary care.