P0893BONE EFFECTS AND SAFETY OF ONE YEAR DENOSUMAB THERAPY IN A COHORT OF RENAL TRANSPLANTED PATIENTS: AN OBSERVATIONAL MONOCENTRIC STUDY

Abstract

Abstract Background and aims Bone and mineral metabolism (MM) disorders are relevant problems in renal transplanted patients (RTxp). In our observational monocentric study, we evaluated the effects on femoral and lumbar bone mineral density (BMD) and on MM parameters, and the safety of one year-treatment with Denosumab (DB) in a cohort of RTxp. Method We recorded data about 32 RTxp treated with DB in our Center in the last year. RTxp were evaluated for BMD and T-score (Ts) before the start (T0) and after 12 months (T12) of treatment. Osteopenia was defined, at femoral (F-OPN) and lumbar (L-OPN) sites as Ts:-1>Ts>-2.5 whereas osteoporosis, in the same sites (F-OPS and L-OPS) as Ts<-2.5. X ray evaluation for spontaneous vertebral fractures (sVF) was made at T0 and, in 25 RTxp repeated at T12. MM and renal function parameters (serum creatinine, sCr and daily urinary protein excretion, ProtU) were recorded at T0 and after 1,3,6, and 12 months of therapy. The clinical indications for DB therapy, in the presence of Ca>9.0 mg/dL were the finding at T0 of: 1) F-OPS and/or V-OPS; 2) sVF. During the year of treatment, hypocalcemic (HpCa=Ca<8.0 mg/dL) episodes, infections, graft rejections and loss and RTxp survival were monitored. Results The cohort was composed mainly by females (n=21). The time of RTx was 144[59-232]mths. Steroid therapy was prescribed in 30 RTxp (93%), 22(68%) and in 2 (6%) RTxp were taking 25OHD and 1-25OH. Three RTxp (9%) were receiving Ca supplements. Bisphosphonate therapy was reported in 15 RTxp (46%) in the year before DB start. At T0, 25(78%) and 7 (22%) RTxp had F-OPS and F-OPN. Twenty-three (71%) and 6 (20%) RTxp had L-OPS and L-OPN. In 3 RTxp normal lumbar T-score was found. sVF were present in 17 RTxp (53%). Ca and P were 9.6±0.6 mg/dL and 3.1±0.6 mg/dL whereas PTH, ALP and 25OHD were 64±32 pg/mL, 80±37 U/L and 28±16 mg/dL. SCr and Prot-U were 1,32±0,4 mg/dL and 0,23±0,16 g/24h. At T12, F-Ts increased significantly (T0: -3.0[-3.5/-2.5] vs T12:-2.8[-3.5/-2.4) as like as V-Ts (T0: -3.0[-3.7/-1.9] vs T12:-2.8[-3.0/-1.6) both p<0.0001. A significant increase was found also in BMD: F-BMD +2.4%[-1.1%/+13%] (p<0.0001), V-BMD +2.6%[-3.4%/+12%] (p=0.009). The prevalence of F-OPS reduced from 78% to 73% (p<0.0001) and 4 RTxp ameliorated their Ts category. Prevalence of V-OPS reduced to 53% at T12 from 71% (p<0.001), and 4 RTxp ameliorated their Ts category. In 2 RTxp were found novel sVF. During the treatment no significant modifications of Ca were found, with only a slight but significant difference between T0 and T12 (T12 Ca: 9.22±1.17, p=0.01). PTH and ALP were significantly higher at T3, T6 and T12 respect T0. No differences in 25OH, sCr and ProtU were found. During the year of treatment, in 3 RTxp 25OHD supplementation was started. No one required novel Ca supplementation. DB therapy wasn’t associated to HpCa episodes. Four RTxp had infections during the time of treatment (mean time of DB treatment:114 days). They had positive pathologic anamnesis for urinary tract infections (UTI). Two of them had symptomatic UTI and 2 required hospitalization for sepsis. No biopsy proven graft rejections were observed during the time of treatment and no graft loss or RTxp death were reported. Conclusions The preliminary results presented in our study, limited by the monocentric, not randomized design and by the smallness of the cohort, reported a good bone efficacy of DB in RTxp, especially at lumbar level. The therapy was characterized by a good general safety. Future longer and randomized studies, involving more RTxp might elucidate the possible primary role of DB in the treatment of bone disorders in RTxp.