P0894AEFFECTS OF DENOSUMAB ON BONE MINERAL DENSITY AND LOW ENERGY FRACTURES IN KIDNEY TRANSPLANT PATIENTS: SAFE AND EFFECTIVE

Abstract

Abstract Background and Aims Fractures are a disabling clinical outcome after kidney transplantation (KTx), with incidence 5 to 34 times higher expected in males and females, respectively. Denosumab, a fully human monoclonal antibody that binds to RANKL with high affinity and specificity, blocking the interaction of RANKL with RANK, mimicking the endogenous effects of osteoprotegerina, increase bone mineral density; however, its effects to reduce the risk of vertebral fractures and ameliorate BMD remain undefinite in the KTx. Method Thirteen kidney recipients (aged from 50 to 79 yy, 6.2 + 5.5 (SD) yy after KTx), 6 M and 7 F (all postmenopausal) with nearly normal renal function (creat. 1.1+-0.31 mg/dl), affected by low energy vertebral fractures (21 dorsal and 1 lumbar vertebrae), evaluated by morphometric X-ray absorptiometry (Hologic DQR-4500A), were treated with denosumab (four 60-mg doses of denosumab Q6M) over 24 months. Data for vertebral heights and height ratios (P-A), covering 9 vertebral bodies were obtained, besides the data of vertebral, femural and radius BMD.The immunosuppressive regimen consisted of CNI (TAC or CsA), MMF and 8 out of 13 patients were still taking prednisone. Bone mineral metabolism parameters (whole-PTH, 25OHD3 and alcaline phosphatase) were also evaluated. Results No sides effects were observed, and all Patients concluded the study.After two years of denosumab treatment, we observed a significative reduction of vertebral T-score (from -2.12 +- 0.35 (SE) to -1.67+-0.35; p< .02), while T score of femural and radius did not show significative variation (-1.86+-0.21 versus -1.84+- 0.23 and -3.04+-0.42 versus -3.19+-0.45, respectively). The number of low energy vertebral fractures, basal versus two years control, had increased for only two dorsal vertebral fractures. However, to one of two subjects, with new dorsal vertebral fractures, was administered high dose of methylprednison for a severe kidney reject. No variations were observed in whole-PTH (89.31+-19.9 versus 68.38+-9.8 pg/ml), 25OHD3 (24.02+-2.75 versus 26.67+-2.29 ug/dl) and alcaline phosphatase (78.46+-12.73 versus 56.77+-7.14 UI). Conclusion Treatment with denosumab improve BMD at vertebral site in KTx, despite continuous steroid therapy and reduce the risk of new low energy vertebral fractures