title: Eldecalcitol reduces osteoporotic fractures by unique mechanisms.
abstract: Eldecalcitol shows higher binding affinity for vitamin D-binding protein (DBP), tighter binding to vitamin D receptor (VDR), and resistance to metabolic degradation via 24-hydroxylation. In silico analysis of the mode of binding demonstrated that the 3-hydroxypropyloxy (3-HP) group of eldecalcitol offers additional hydrogen bond and CH-π interaction for the binding to DBP and VDR. However, the 3-HP group interferes with the binding of eldecalcitol to CYP24A1, causing poor metabolic clearance of eldecalcitol by this enzyme. These characteristics may contribute to the stronger effect of eldecalcitol than calcitriol. The present post-hoc analysis also demonstrate that the incidence of hypercalcemia and hypercalciuria is slightly higher in eldecalcitol than in alfacalcidol group especially in patients with CKD stage 3B, that both serum and urinary calcium return to the baseline levels shortly after cessation of the treatment in both treatment groups, that the incidence of urolithiasis is higher in patients with higher eGFR and is similar between alfacalcidol and eldecalcitol groups, and that eGFR is transiently reduced by both alfacalcidol and eldecalcitol treatment especially among patients with higher eGFR but recovers after the end of both treatment. Eldecalcitol can be used for the treatment of osteoporosis without Ca supplementation to reduce the incidence of hypercalcemia and hypercalciuria, and enough hydration is recommended in order to avoid hypercalcemia, urolithiasis and deterioration of renal function.
authors.affiliation: Chugai Pharmaceutical Co., Ltd., Tokyo 103-8324, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kondo
authors.affiliation: Chugai Pharmaceutical Co., Ltd., Tokyo 103-8324, Japan.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Takano
authors.affiliation: Chugai Pharmaceutical Co., Ltd., Tokyo 103-8324, Japan.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Ono
authors.affiliation: Chugai Pharmaceutical Co., Ltd., Tokyo 103-8324, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Saito
authors.affiliation: Fujii Memorial Institute of Medical Research, University of Tokushima, Tokushima 770-8503, Japan. Electronic address: toshio.matsumoto@tokushima-u.ac.jp.
authors.forename: Toshio
authors.initials: T
authors.lastname: Matsumoto
mesh_terms: D000368:Aged; D015519:Bone Density / Q000187:drug effects; D002117:Calcitriol / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D017326:Clinical Trials, Phase III as Topic; D018360:Crystallography, X-Ray; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D008297:Male; D008875:Middle Aged; D010024:Osteoporosis / Q000188:drug therapy* / Q000378:metabolism; D058866:Osteoporotic Fractures / Q000378:metabolism / Q000517:prevention & control*; D011487:Protein Conformation / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D018167:Receptors, Calcitriol / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D014809:Vitamin D-Binding Protein / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D065668:Vitamin D3 24-Hydroxylase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014815:Vitamins / Q000494:pharmacology
chemical_list: D012333:RNA, Messenger; D018167:Receptors, Calcitriol; D014809:Vitamin D-Binding Protein; D014815:Vitamins; D014807:Vitamin D; C585549:CYP24A1 protein, human; D065668:Vitamin D3 24-Hydroxylase; D002117:Calcitriol; C547512:eldecalcitol; D002118:Calcium
keywords: Hypercalcemia; Hypercalciuria; Renal function; Vitamin D 24-hydroxylase (CYP24A1); Vitamin D receptor (VDR); Vitamin D-binding protein (DBP)