MO581ASSOCIATION OF ETELCALCETIDE WITH ADYNAMIC BONE DISEASE IN DIABETIC PATIENTS : A MULTI-CENTRIC STUDY
Authors: Leonardi Giuseppe , Montanaro Alessio , Spinelli Alessandra , Covella Patrizia , Balestra Cosima , Flores Antonio , Di Renzo Brigida , Schiavone Palmira , Mariotti Amalia , De Giorgi Annarita , Figlia Irma , D'Anello Emanuela , Coppolino Giuseppe , Vernaglione Luigi 
Published: May 2021

Abstract

Background and Aims
Several dialysis patients frequently suffer of different mineral and bone disorders (CKD-MBD) associated with secondary hyperparathyroidism (sHPT). Among CKD-MBD, adynamic bone disease (ABD) is an alteration characterized by reduced osteblasts and osteoclasts, no accumulation of osteoid and low bone turnover. The histologic pattern of ABD is generally associated to low levels of PTH.
Etelcalcetide is a novel second-generation calcimimetic given intravenously after each hemodialysis session that has a longer elimination half-life than cinacalcet. Plasmatic concentration remains stable from 24 h to 48 h after injection. One potential risk of calcimimetics, such as etelcalcetide, is the dramatic and sustained PTH lowering, which could lead to the induction of adynamic bone disease (ABD). ABD and elevated serum levels of advanced glycation end products (AGEs) often are found in patients with renal failure caused by diabetic nephropathy since AGEs are involved in the pathogenesis of ABD by inhibiting osteoblastic activity and by parathyroid hormone secretion in response to hypocalcemia. So, diabetic patients treated with etelcalcetide could be considered at increased risk of developing ABD.
Aim of our study was to verify the incidence of adynamic bone disease, (defined by low PTH levels) in prevalent diabetic and non-diabetic HD patient of three large community Hospital.

Method
Data were collected from 3 dialysis units with n = 130 patients on the charge for a period of 1 year from start of the calcimimetic. A total of 40 patients ( 23 male, 17 female) on etelcalcetide were enrolled (21 Diabetic, 19 non diabetic patients). Time points of assessment included 1-3-6-12 months. Patients were 18-years-old or older; they were on stable doses of active vitamin D analogs, phosphorus binders, a supplement of oral calcium, and calcium concentration in dialysate (1.25–1.50 mmol/L)

Results
Median age was 55,9 years and dialysis vintage was 4.6 year. 59,5% percent of patients switched from cinacalcet to etelcalcetide (90 days from last cinacalcet prescription); the remaining patients were calcimimetic naive. 40% of patients had a history of at least one cardiovascular event 61.5% had a starting etelcalcetide dose of 5 mg and the median weekly dose was 7.5 mg (range: 2.5-15 mg).
On Diabetic Group: mean PTHi, Ca2+ and P before calcimimetic start was respectively 844±479,30 pg /mL , 9,95±0,97 mg/dl , 5,02±0,99 mg/dl. In non diabetic patients: mean PTHi, Ca2+ and P before calcimimetic start was: 793,36±534,41 150 pg /mL, 9,33±0,70 mg/dl, 5,9±1,17 mg/dl

Conclusion
Results of our study show that after 1 year of etelcalcetide treatment, levels of PTHi are lower more in non-diabetic patients, ( M12: 473±340,08 vs 253,13 + 98,87 p:0.042) despite scientific evidence currently supporting hypothesis that osteoblastic activity is reduced by AGES and ABD risk is increased in diabetic nephropathy. Therefore, etelcalcetide could be used safely in diabetic patients and could even protect from the risk of development ABD. However, further studies are required to validate this hypothesis.
Results are shown in the following table: