Eldecalcitol for the treatment of osteoporosis

Figures & data

Figure 1 Chemical structures of native vitamin D₃ and active vitamin D₃ analogs.

Table 1 Biological evaluation of eldecalcitol

Characteristics	1,25(OH)2D3	Eldecalcitol
Affinity to vitamin D receptors	100	44.6
Affinity to vitamin D-binding protein	100	422
Inhibition of parathyroid hormone secretion	100	3.54

Note: Each value of eldecalcitol represents the percentage relative to that of 1.25(OH)₂D₃.

Adapted from J Steroid Biochem Mol Biol, 103(3–5), Hatakeyama S, Nagashima S, Imai N, et al, Synthesis and biological evaluation of a 3-positon epimer of 1alpha, 25-dihydroxy-2beta-(3-hydroxypropoxy) vitamin D3 (ED-71), 222–226, Copyright (2007), with permission from Elsevier.³⁴

Abbreviation: 1,25(OH)₂D₃, 1,25-dihydroxyvitamin D₃.

Figure 2 Incidence of new vertebral fractures in the alfacalcidol (1.0 μg/day) group and the eldecalcitol (0.75 μg/day) group during the 3-year study period. Kaplan–Meier estimates of the incidence of new vertebral fractures.

Adapted from Matsumoto T, Ito M, Hayashi Y, et al. A new active vitamin D3 analog, eldecalcitol, prevents the risk of osteoporotic fractures – a randomized, active comparator, double-blind study. Bone. 2011;49(4):605–612, with permission from Elsevier.⁵¹

Abbreviation: CI, confidence interval.

Figure 3 Incidence of all nonvertebral fractures, nonvertebral fractures at three major sites (humerus, wrist, hip), and wrist fracture in the alfacalcidol (1.0 μg/day) group and the eldecalcitol (0.75 μg/day) group during the 3-year study period.

Notes: *P = 0.009. Data from.⁵¹

Abbreviations: HR, hazard ratio; CI, confidence interval.

Figure 4 Effects of eldecalcitol and alfacalcidol on BMD (A and B) and bone turnover markers (C and D) during the 3-year study period.

Adapted from Matsumoto T, Ito M, Hayashi Y, et al. A new active vitamin D3 analog, eldecalcitol, prevents the risk of osteoporotic fractures – a randomized, active comparator, double-blind study. Bone. 2011;49(4):605–612, with permission from the Elsevier.⁵¹

Notes: Mean percent change from baseline in lumbar spine (A) and total hip (B) BMD in the eldecalcitol group (closed circle) and the alfacalcidol group (open circle) during the study period. Median percent change from baseline in bone turnover markers including serum BSAP (C) and urinary NTX (D) in the eldecalcitol group (closed circle) and the alfacalcidol group (open circle) during the study period are shown. Data are means ± SE for lumbar spine and total hip BMD, and medians for bone turnover markers. *P < 0.001 in comparison with alfacalcidol.
Abbreviations: BMD, bone mineral density; BSAP, bone-specific alkaline phosphatase; NTX, urinary N-terminal propeptide of type I collagen; SE, standard error.

Table 2 Incidence of adverse events

Event	Eldecalcitol (N = 528)	Alfacalcidol (N = 526)	Risk ratio	95% confidence interval
General
Any adverse events	520 (98.5%)	518 (98.5%)	1.00	0.99–1.02
Nasopharyngitis	332 (62.9%)	312 (59.3%)	1.06	0.96–1.17
Contusion	119 (22.5%)	118 (22.4%)	1.00	0.80–1.26
Urine calcium increased	135 (25.6%)	82 (15.6%)	1.64	1.28–2.10
Blood calcium increased	111 (21.0%)	71 (13.5%)	1.56	1.19–2.04
Back pain	72 (13.6%)	81 (15.4%)	0.89	0.66–1.19
Osteoarthritis	82 (15.5%)	70 (13.3%)	1.17	0.87–1.57
Arthralgia	54 (10.2%)	52 (9.9%)	1.03	0.72–1.48
Eczema	54 (10.2%)	50 (9.5%)	1.08	0.75–1.55
Constipation	39 (7.4%)	58 (11.0%)	0.67	0.45–0.99
Headache	51 (9.7%)	39 (7.4%)	1.30	0.87–1.94
Diarrhea	50 (9.5%)	38 (7.2%)	1.31	0.88–1.96
Gastroenteritis	46 (8.7%)	41 (7.8%)	1.12	0.75–1.67
Periarthritis	45 (8.5%)	41 (7.8%)	1.09	0.73–1.64
Spinal fracture	38 (7.2%)	46 (8.7%)	0.82	0.54–1.24
Cystitis	36 (6.8%)	44 (8.4%)	0.82	0.53–1.24
Hypertension	41 (7.8%)	36 (6.8%)	1.13	0.74–1.75
Gastritis	34 (6.4%)	40 (7.6%)	0.85	0.54–1.32
Pain in extremity	31 (5.9%)	40 (7.6%)	0.77	0.49–1.21
Stomatitis	37 (7.0%)	32 (6.1%)	1.15	0.73–1.82
Dermatitis contact	38 (7.2%)	28 (5.3%)	1.35	0.84–2.17
Insomnia	34 (6.4%)	32 (6.1%)	1.06	0.66–1.69
Dizziness	29 (5.5%)	32 (6.1%)	0.90	0.55–1.47
Cataract	32 (6.1%)	27 (5.1%)	1.18	0.72–1.94
Joint sprain	29 (5.5%)	28 (5.3%)	1.03	0.62–1.71
Spinal osteoarthritis	23 (4.4%)	34 (6.5%)	0.67	0.40–1.13
Stomach discomfort	27 (5.1%)	25 (4.8%)	1.08	0.63–1.83
Exanthem	15 (2.8%)	33 (6.3%)	0.45	0.25–0.82
Serious adverse events	110 (20.8%)	134 (25.5%)	0.82	0.66–1.02
Death	4 (0.8%)	6 (1.1%)	0.66	0.19–2.34
Cancer	11 (2.1%)	16 (3.0%)	0.68	0.32–1.46
Discontinued due to adverse events	31 (5.9%)	40 (7.6%)	0.77	0.49–1.21
Calcium-related adverse events
Urolithiasis	7 (1.3%)	5 (1.0%)	1.39	0.45–4.37

Note: Adapted from Matsumoto T, Ito M, Hayashi Y, et al. A new active vitamin D3 analog, eldecalcitol, prevents the risk of osteoporotic fractures – a randomized, active comparator, double-blind study. Bone. 2011;49(4):605–612, with permission from Elsevier.⁵¹

HatakeyamaSNagashimaSImaiNSynthesis and biological evaluation of a 3-positon epimer of 1alpha,25-dihydroxy-2beta-(3-hydroxypropoxy)vitamin D3 (ED-71)J Steroid Biochem Mol Biol20071033–522222617207991

 PubMed Web of Science ®Google Scholar

MatsumotoTItoMHayashiYA new active vitamin D3 analog, eldecalcitol, prevents the risk of osteoporotic fractures – a randomized, active comparator, double-blind studyBone201149460561221784190

 PubMed Web of Science ®Google Scholar