MO199DENOSUMAB: NOVEL APPROACH TO TREATMENT OF OSTEOPOROSIS IN RENAL DISEASE

Background and Aims Denosumab is a fully human monoclonal antibody to the receptor activator of nuclear factor kappa-B ligand (RANKL), an osteoclast differentiating factor. It inhibits osteoclast formation, decrease bone resorption, increase bone mineral density (BMD), and reduce the risk of fracture. There is no restriction of its use in patients with renal disease, for whom biphosphonates are considered controindicated. The aim of our study was to evaluate the effectiveness in reducing facture risk and safety of Denosumab in patients with Osteoporosis and renal disease. Method This is a prospective analysis of 17 patients with Osteoporosis (average T-score below -2.5) admitted to our Nephrology Department for CKD in the last four years. in Vasculitis, Renal Allograft Recipients. Patients with severe Hyperparatiroidism were excluded. We estimated creatinine clearance (eGFR) using Cockcroft-Gault and classified levels of kidney function using the modified National Kidney Foundation classification of CKD. All patients were adequately supplemented with calcium and vitamin D before and while taking Denosumab 60 mg every 6 months. The primary endpoint is the change in bone mineral density (BMD) at one and two years. Secondary endpoints include changes in bone mineral metabolism parameters (Ca, P, PTHi, 25-OH VitD), incidence of fractures, and renal/allograft fuction at one and two years. Results The mean age was 52.5±4 years and 8/17 (47%) were females. N.13 patients (76.5%) were renal transplant recipients (RTR) on standard triple immunosoppression including steroids (prednisone 5 mg/day), CNI and MMF, with average eGFR 65.7±12.5 ml/min. N.2 patients (11.75%) were in hemodialysis. N.2 patients (11.75%) with Anca Vasculitis on steroid therapy and average eGFR 35.6±7.2 ml/min. All patients enrolled were with a BMD T-score of greater than -4.0 and less than -2.5. Only 2 patients had a history of fractures confirmed by a radiology report. Baseline parameters: calcium 9.8±0.32 mg/dl, phosphate 3.9±0.8 mg/dl, PTHi 137±91.0 ng/L, 25-OH VitD 18.3±8.9 ng/mL. From baseline at 1 month there were an increase in PTH and a decrease in calcemia in only 2 transplant recipients (CKD II and IV), that improved with an increased dose of Vit D. There were no significant difference in baseline bone mineral metabolism parameters to year 1 and 2 in all other patients. We found no difference in eGFR and proteinuria from baseline to 1 and 2 years in RTR and ANCA vasculitis. Significant improvement in T-score was observed at 1 year and 2 years (< -1) in all patients. No one discontinued therapy for adverse events. Conclusion Denosumab may have advantages in patients with kidney dysfunction, because not excreted by the kidney and there is no need for dose adjustment. This prospective study showed a significant improvement in osteoporosis (at Dexa mean T-score ≤ -1), but particular attention should be paid to ensuring that patients are calcium and Vitamin D replete.