Journal: Clinical Pharmacology in Drug Development

Article Title: Pharmacokinetic and Bioequivalence Study of Eldecalcitol Soft Capsules in Healthy Chinese Subjects

doi: 10.1002/cpdd.1159

Figure Lengend Snippet: Comparison of PK Parameters of Eldecalcitol in Healthy Chinese Subjects After a Single Oral Administration of a 0.75‐µg Eldecalcitol Capsule (Test Formulation or Reference Formulation) Under Fasting and Fed Conditions

Article Snippet: All 28 subjects participating in the fasting trial were randomly assigned to two groups to receive a single dose of a 0.75‐μg reference eldecalcitol soft capsule (R; Edirol ® , Chugai Pharmaceutical Co., Ltd, Fujieda City, Japan) or test capsule (T; Wenzhou Haihe Pharmaceutical Co., Ltd, Wenzhou, China) with approximately 240 mL of warm water in the first treatment period and to receive another formulation in the second treatment period.

Techniques: Comparison, Formulation

Journal: Journal of Histochemistry and Cytochemistry

Article Title: Histological Effects of the Combined Administration of Eldecalcitol and a Parathyroid Hormone in the Metaphyseal Trabeculae of Ovariectomized Rats

doi: 10.1369/0022155418806865

Figure Lengend Snippet: Tibial BMD, serum concentration of OCN, Ca, and Pi, and urinary DPD in OVX, PTH, eldecalcitol, and combined groups. All groups treated with PTH, eldecalcitol, and a combination of PTH and eldecalcitol show a higher index of BMD compared with the OVX group at both 4 and 8 weeks. Above all, the combined group reveals the highest value at both time points (A and B). Serum concentration of OCN is significantly higher in the PTH and combined group compared with that in the OVX and eldecalcitol groups at both 4 and 8 weeks (C and D). By contrast, the index of DPD/Cre is significantly reduced in the eldecalcitol group at 4 weeks and in the eldecalcitol and combined group at 8 weeks compared with that in the OVX group (E and F). The index of serum Ca is significantly elevated in the eldecalcitol group at 4 weeks and in the eldecalcitol and combined group at 8 weeks compared with that in the OVX group (G and H). Abbreviations: BMD, bone mineral density; OCN, osteocalcin; DPD, deoxypyridinoline; OVX, ovariectomy; PTH, parathyroid hormone.

Article Snippet: The rats were divided into the following groups with eight to nine animals each and treated from 4 weeks after operation (13 weeks old): Sham group (Sham operated), OVX group, PTH group (OVX administered 10 μg/kg/day of hPTH(1-34) five times per week; the dosage of the drug was decided according to the previous reports 20 – 21 ) (Peptide Institute Inc., Osaka, Japan), eldecalcitol group (OVX administered 20 ng/kg/day of eldecalcitol five times per week, as reported by Takeda et al. 22 ), or a combined group (OVX administered 10 μg/kg/day of hPTH(1-34) and 20 ng/kg/day of eldecalcitol for 4 or 8 weeks).

Techniques: Concentration Assay

Journal: Journal of Histochemistry and Cytochemistry

Article Title: Histological Effects of the Combined Administration of Eldecalcitol and a Parathyroid Hormone in the Metaphyseal Trabeculae of Ovariectomized Rats

doi: 10.1369/0022155418806865

Figure Lengend Snippet: Bone histology and bone histomorphometry of tibiae in Sham, OVX, PTH, eldecalcitol, and combined groups (4 weeks). H&E staining demonstrates the markedly reduced metaphyseal trabeculae in the OVX group compared with that in the Sham group (A, B, F, and G). The PTH, eldecalcitol, and combined groups show the induced volume of metaphyseal trabeculae (C–E and H–J). The indices of BV/TV and Tb.N are significantly increased in the PTH, eldecalcitol, and combined groups compared with those in the OVX group (K and M). Tb.Th is higher in the PTH, eldecalcitol, and combined groups compared with that in the OVX group, whereas the index of Tb.Th is significantly lower in the eldecalcitol group compared with that in the PTH and combined groups (L). Tb.Sp is lower in the PTH, eldecalcitol, and combined groups compared with that in the OVX group (N). meta: metaphysis; Bars: A–E: 1 mm, F–J: 300 µm. Abbreviations: OVX, ovariectomy; PTH, parathyroid hormone; H&E, hematoxylin and eosin; BV/TV, bone volume/tissue volume; Tb.N, trabecular number; Tb.Th, trabecular thickness; Tb.Sp, trabecular separation.

Article Snippet: The rats were divided into the following groups with eight to nine animals each and treated from 4 weeks after operation (13 weeks old): Sham group (Sham operated), OVX group, PTH group (OVX administered 10 μg/kg/day of hPTH(1-34) five times per week; the dosage of the drug was decided according to the previous reports 20 – 21 ) (Peptide Institute Inc., Osaka, Japan), eldecalcitol group (OVX administered 20 ng/kg/day of eldecalcitol five times per week, as reported by Takeda et al. 22 ), or a combined group (OVX administered 10 μg/kg/day of hPTH(1-34) and 20 ng/kg/day of eldecalcitol for 4 or 8 weeks).

Techniques: Staining

Journal: Journal of Histochemistry and Cytochemistry

Article Title: Histological Effects of the Combined Administration of Eldecalcitol and a Parathyroid Hormone in the Metaphyseal Trabeculae of Ovariectomized Rats

doi: 10.1369/0022155418806865

Figure Lengend Snippet: Bone histology and bone histomorphometry of tibiae in Sham, OVX, PTH, eldecalcitol, and combined groups (8 weeks). At 8 weeks, the combined group shows a thickened metaphyseal trabeculae (A–J) and the highest value of BV/TV and Tb.Th (K and L) compared with the other groups. The index of Tb.N in the PTH and combined groups is elevated (M), but Tb.Sp consistently decreased in those groups (N). meta: metaphysis; Bars: A–E: 1 mm, F–J: 300 µm. Abbreviations: OVX, ovariectomy; PTH, parathyroid hormone; BV/TV, bone volume/tissue volume; Tb.Th, trabecular thickness; Tb.N, trabecular number; Tb.Sp, trabecular separation.

Article Snippet: The rats were divided into the following groups with eight to nine animals each and treated from 4 weeks after operation (13 weeks old): Sham group (Sham operated), OVX group, PTH group (OVX administered 10 μg/kg/day of hPTH(1-34) five times per week; the dosage of the drug was decided according to the previous reports 20 – 21 ) (Peptide Institute Inc., Osaka, Japan), eldecalcitol group (OVX administered 20 ng/kg/day of eldecalcitol five times per week, as reported by Takeda et al. 22 ), or a combined group (OVX administered 10 μg/kg/day of hPTH(1-34) and 20 ng/kg/day of eldecalcitol for 4 or 8 weeks).

Techniques:

Journal: Journal of Histochemistry and Cytochemistry

Article Title: Histological Effects of the Combined Administration of Eldecalcitol and a Parathyroid Hormone in the Metaphyseal Trabeculae of Ovariectomized Rats

doi: 10.1369/0022155418806865

Figure Lengend Snippet: Distribution of ALPase-reactive cells and the index of Ob.S/BS in the tibiae of OVX, PTH, eldecalcitol, and combined groups (8 weeks). There is an intense immunoreactivity of ALPase on the bone surface in the tibial metaphysis of the PTH and combined groups (arrows, B, D, F, and H) but not in that of the Sham and eldecalcitol groups (A, C, E, and G) at 8 weeks after the administration. The indices of Ob.S in the PTH and combined groups are higher than in the Sham and eldecalcitol groups (I). meta: metaphysis. Bars: A–D: 250 µm, E–H: 25 µm. Abbreviations: ALPase, alkaline phosphatase; Ob.S/BS, osteoblastic surface/bone surface; OVX, ovariectomy; PTH, parathyroid hormone.

Article Snippet: The rats were divided into the following groups with eight to nine animals each and treated from 4 weeks after operation (13 weeks old): Sham group (Sham operated), OVX group, PTH group (OVX administered 10 μg/kg/day of hPTH(1-34) five times per week; the dosage of the drug was decided according to the previous reports 20 – 21 ) (Peptide Institute Inc., Osaka, Japan), eldecalcitol group (OVX administered 20 ng/kg/day of eldecalcitol five times per week, as reported by Takeda et al. 22 ), or a combined group (OVX administered 10 μg/kg/day of hPTH(1-34) and 20 ng/kg/day of eldecalcitol for 4 or 8 weeks).

Techniques:

Journal: Journal of Histochemistry and Cytochemistry

Article Title: Histological Effects of the Combined Administration of Eldecalcitol and a Parathyroid Hormone in the Metaphyseal Trabeculae of Ovariectomized Rats

doi: 10.1369/0022155418806865

Figure Lengend Snippet: Histological aspects and static parameters of bone formation in the tibiae of OVX, PTH, eldecalcitol, and combined groups (8 weeks). The double labeling of calcein and tetracycline shows the scalloped shape, indicating remodeling-based bone formation in the OVX and PTH groups (A, B, E, and F), while the eldecalcitol group reveals focal convex labeling indicating minimodeling-based bone formation (C and G). The combined group demonstrates both focal convex and scalloped labeling in the metaphyseal trabeculae (D and H). The OVX and PTH groups show the highest value of MAR and BFR/BS, while the eldecalcitol and combined groups demonstrate lower MAR and BFR/BS values (I and J). Bars: A–H: 25 µm. Abbreviations: OVX, ovariectomy; PTH, parathyroid hormone; MAR, mineral apposition rate; BFR/BS, bone formation rate/bone surface; BM: bone matrix.

Article Snippet: The rats were divided into the following groups with eight to nine animals each and treated from 4 weeks after operation (13 weeks old): Sham group (Sham operated), OVX group, PTH group (OVX administered 10 μg/kg/day of hPTH(1-34) five times per week; the dosage of the drug was decided according to the previous reports 20 – 21 ) (Peptide Institute Inc., Osaka, Japan), eldecalcitol group (OVX administered 20 ng/kg/day of eldecalcitol five times per week, as reported by Takeda et al. 22 ), or a combined group (OVX administered 10 μg/kg/day of hPTH(1-34) and 20 ng/kg/day of eldecalcitol for 4 or 8 weeks).

Techniques: Labeling

Journal: Journal of Histochemistry and Cytochemistry

Article Title: Histological Effects of the Combined Administration of Eldecalcitol and a Parathyroid Hormone in the Metaphyseal Trabeculae of Ovariectomized Rats

doi: 10.1369/0022155418806865

Figure Lengend Snippet: Histological assessment of osteoblast and osteoclast in the tibial metaphyseal trabeculae of the PTH, eldecalcitol, and combined groups (8 weeks). The PTH-group demonstrates cuboidal mature osteoblasts, a thick layer of preosteoblasts (arrows) and osteoclasts possessed well-developed ruffled borders on the bone surface (A, B, G, and H). By contrast, the eldecalcitol group shows flattened osteoblasts, a few preosteoblasts, and osteoclasts often lacking ruffled borders (C, F, I, and J). The combined group reveals mature osteoblasts, a few layers of preosteoblasts (arrow), and osteoclasts often lacking ruffled borders, such as in between the PTH and eldecalcitol groups (E, F, K, and L). Abbreviations: PTH, parathyroid hormone; OB, osteoblast; pre-OB, preosteoblast; OC, osteoclast; RB, ruffled border. Bars: A–F: 10 µm, G–I: 5 µm.

Article Snippet: The rats were divided into the following groups with eight to nine animals each and treated from 4 weeks after operation (13 weeks old): Sham group (Sham operated), OVX group, PTH group (OVX administered 10 μg/kg/day of hPTH(1-34) five times per week; the dosage of the drug was decided according to the previous reports 20 – 21 ) (Peptide Institute Inc., Osaka, Japan), eldecalcitol group (OVX administered 20 ng/kg/day of eldecalcitol five times per week, as reported by Takeda et al. 22 ), or a combined group (OVX administered 10 μg/kg/day of hPTH(1-34) and 20 ng/kg/day of eldecalcitol for 4 or 8 weeks).

Techniques:

Journal: Journal of Histochemistry and Cytochemistry

Article Title: Histological Effects of the Combined Administration of Eldecalcitol and a Parathyroid Hormone in the Metaphyseal Trabeculae of Ovariectomized Rats

doi: 10.1369/0022155418806865

Figure Lengend Snippet: Distribution of TRAPase-positive osteoclasts and the index of Oc.S/BS and ES/BS in the tibiae of OVX, PTH, eldecalcitol, and combined groups (8 weeks). There are abundant TRAPase-positive osteoclasts in the tibial metaphysis of the OVX group compared with the other groups (B and F). The indices of Oc.S/BS and ES/BS are consistently highest in the OVX group (I and J). meta: metaphysis; Bars: A–D: 250 µm, E–H: 25 µm. Abbreviations: TRAPase, Tartrate-resistant acid phosphatase; Oc.S/BS, osteoclastic surface/bone surface; ES/BS, eroded surface/bone surface; OVX, ovariectomy; PTH, parathyroid hormone.

Article Snippet: The rats were divided into the following groups with eight to nine animals each and treated from 4 weeks after operation (13 weeks old): Sham group (Sham operated), OVX group, PTH group (OVX administered 10 μg/kg/day of hPTH(1-34) five times per week; the dosage of the drug was decided according to the previous reports 20 – 21 ) (Peptide Institute Inc., Osaka, Japan), eldecalcitol group (OVX administered 20 ng/kg/day of eldecalcitol five times per week, as reported by Takeda et al. 22 ), or a combined group (OVX administered 10 μg/kg/day of hPTH(1-34) and 20 ng/kg/day of eldecalcitol for 4 or 8 weeks).

Techniques:

Journal: Journal of Histochemistry and Cytochemistry

Article Title: Histological Effects of the Combined Administration of Eldecalcitol and a Parathyroid Hormone in the Metaphyseal Trabeculae of Ovariectomized Rats

doi: 10.1369/0022155418806865

Figure Lengend Snippet: Histological analysis on osteoblastic cells and bone mineralization in the tibial metaphyseal trabeculae of the PTH, eldecalcitol, and combined groups (8 weeks). Von Kossa staining demonstrates the clear and smooth calcification front of the mineralized bone matrix in the eldecalcitol and combined groups (arrowheads, B and C), while it shows the rough surface of a mineralized bone matrix in the PTH group (arrowheads, A). ALPase and PCNA double-positive preosteoblasts are present in the both PTH and combined groups (arrow, D and F); however, not so many are seen in the combined group compared with the PTH group. In the eldecalcitol group, there is a thin layer of ALPase-positive osteoblasts on the bone surface (E). Bars: A–F: 10 µm. Abbreviations: PTH, parathyroid hormone; ALPase, alkaline phosphatase; PCNA, proliferating cell nuclear antigen; OB: osteoblast, BM: bone matrix.

Article Snippet: The rats were divided into the following groups with eight to nine animals each and treated from 4 weeks after operation (13 weeks old): Sham group (Sham operated), OVX group, PTH group (OVX administered 10 μg/kg/day of hPTH(1-34) five times per week; the dosage of the drug was decided according to the previous reports 20 – 21 ) (Peptide Institute Inc., Osaka, Japan), eldecalcitol group (OVX administered 20 ng/kg/day of eldecalcitol five times per week, as reported by Takeda et al. 22 ), or a combined group (OVX administered 10 μg/kg/day of hPTH(1-34) and 20 ng/kg/day of eldecalcitol for 4 or 8 weeks).

Techniques: Staining

Journal: Osteoporosis and Sarcopenia

Article Title: Comparative effect of eldecalcitol and alfacalcidol on bone microstructure: A preliminary report of secondary analysis of a prospective trial

doi: 10.1016/j.afos.2021.05.003

Figure Lengend Snippet: Baseline clinical characteristics of subjects included in HR-pQCT analysis.

Article Snippet: Eligible patients were randomly assigned to either daily eldecalcitol treatment group [eldecalcitol 0.75 μg (Fujieda Plant of Chugai Pharma Manufacturing Co., Ltd., Fujideda, Japan) + alfacalcidol placebo 1.0 μg (YaoPharma, Chongqing, China)] or daily alfacalcidol treatment group [alfacalcidol 1.0 μg (Iwakuni Factory of Teijin Pharmaceutical Manufacturing Co., Ltd. Iwakuni, Japan) + eldecalcitol placebo 0.75 μg (Fujieda Plant of Chugai Pharma Manufacturing Co, Ltd., Fujieda, Japan)] for 12 months treatment.

Techniques:

Journal: Osteoporosis and Sarcopenia

Article Title: Comparative effect of eldecalcitol and alfacalcidol on bone microstructure: A preliminary report of secondary analysis of a prospective trial

doi: 10.1016/j.afos.2021.05.003

Figure Lengend Snippet: HR-pQCT Measures at Baseline and at 12 Months and comparison of change of HR-pQCT parameters after treatment in two groups.

Article Snippet: Eligible patients were randomly assigned to either daily eldecalcitol treatment group [eldecalcitol 0.75 μg (Fujieda Plant of Chugai Pharma Manufacturing Co., Ltd., Fujideda, Japan) + alfacalcidol placebo 1.0 μg (YaoPharma, Chongqing, China)] or daily alfacalcidol treatment group [alfacalcidol 1.0 μg (Iwakuni Factory of Teijin Pharmaceutical Manufacturing Co., Ltd. Iwakuni, Japan) + eldecalcitol placebo 0.75 μg (Fujieda Plant of Chugai Pharma Manufacturing Co, Ltd., Fujieda, Japan)] for 12 months treatment.

Techniques: Comparison

Journal: Osteoporosis and Sarcopenia

Article Title: Comparative effect of eldecalcitol and alfacalcidol on bone microstructure: A preliminary report of secondary analysis of a prospective trial

doi: 10.1016/j.afos.2021.05.003

Figure Lengend Snippet: Mean percent change from baseline at distal radius and tibia in Tt. vBMD, Tb. vBMD, and Ct. vBMD treated with eldecalcitol and alfacalcidol at the distal radius (A–C) and tibia (D–E). Tt. vBMD, total volumetric bone mineral density; Tb. vBMD, trabecular volumetric bone mineral density; Ct. vBMD, cortical volumetric bone mineral density. Bars represent P value < 0.05 between groups.

Article Snippet: Eligible patients were randomly assigned to either daily eldecalcitol treatment group [eldecalcitol 0.75 μg (Fujieda Plant of Chugai Pharma Manufacturing Co., Ltd., Fujideda, Japan) + alfacalcidol placebo 1.0 μg (YaoPharma, Chongqing, China)] or daily alfacalcidol treatment group [alfacalcidol 1.0 μg (Iwakuni Factory of Teijin Pharmaceutical Manufacturing Co., Ltd. Iwakuni, Japan) + eldecalcitol placebo 0.75 μg (Fujieda Plant of Chugai Pharma Manufacturing Co, Ltd., Fujieda, Japan)] for 12 months treatment.

Techniques:

Journal: Osteoporosis and Sarcopenia

Article Title: Comparative effect of eldecalcitol and alfacalcidol on bone microstructure: A preliminary report of secondary analysis of a prospective trial

doi: 10.1016/j.afos.2021.05.003

Figure Lengend Snippet: Mean percent change from baseline at distal radius in Ct. Ar, Ct.Pm, Ct. Po, Ct. Th treated with eldecalcitol and alfacalcidol at the distal radius (A–D) and tibia (E–H). Ct. Ar, cortical area; Ct.Pm, cortical perimeter; Ct. Po, cortical porosity; Ct. Th, cortical thickness. Bars represent P value < 0.05 between groups.

Article Snippet: Eligible patients were randomly assigned to either daily eldecalcitol treatment group [eldecalcitol 0.75 μg (Fujieda Plant of Chugai Pharma Manufacturing Co., Ltd., Fujideda, Japan) + alfacalcidol placebo 1.0 μg (YaoPharma, Chongqing, China)] or daily alfacalcidol treatment group [alfacalcidol 1.0 μg (Iwakuni Factory of Teijin Pharmaceutical Manufacturing Co., Ltd. Iwakuni, Japan) + eldecalcitol placebo 0.75 μg (Fujieda Plant of Chugai Pharma Manufacturing Co, Ltd., Fujieda, Japan)] for 12 months treatment.

Techniques:

Journal: Osteoporosis and Sarcopenia

Article Title: Comparative effect of eldecalcitol and alfacalcidol on bone microstructure: A preliminary report of secondary analysis of a prospective trial

doi: 10.1016/j.afos.2021.05.003

Figure Lengend Snippet: Mean percent change from baseline in Tb.Ar, Tb.N, Tb.Th, Tb.Sp treated with eldecalcitol and alfacalcidol at the distal radius (A-D) and tibia (E-H). Tb.Ar, trabecular area; Tb.N, trabecular number; Tb.Th, trabecular thickness; Tb.Sp, trabecular separation. Bars represent p value <0.05 between groups.

Article Snippet: Eligible patients were randomly assigned to either daily eldecalcitol treatment group [eldecalcitol 0.75 μg (Fujieda Plant of Chugai Pharma Manufacturing Co., Ltd., Fujideda, Japan) + alfacalcidol placebo 1.0 μg (YaoPharma, Chongqing, China)] or daily alfacalcidol treatment group [alfacalcidol 1.0 μg (Iwakuni Factory of Teijin Pharmaceutical Manufacturing Co., Ltd. Iwakuni, Japan) + eldecalcitol placebo 0.75 μg (Fujieda Plant of Chugai Pharma Manufacturing Co, Ltd., Fujieda, Japan)] for 12 months treatment.

Techniques: