A new active vitamin D3 analog, eldecalcitol, prevents the risk of osteoporotic fractures - A randomized, active comparator, double-blind study

Toshio Matsumoto, Masako Ito, Yasufumi Hayashi, Takako Hirota, Yusuke Tanigawara, Teruki Sone, Masao Fukunaga, Masataka Shiraki, Toshitaka Nakamura

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Abstract

Background: Eldecalcitol is an analog of 1,25-dihydroxyvitamin D 3 that improves bone mineral density; however, the effect of eldecalcitol on the risk of fractures is unclear. The objective of this study is to examine whether eldecalcitol is superior to alfacalcidol in preventing osteoporotic fractures. This trial is registered with ClinicalTrials.gov, number NCT00144456. Methods and results: This 3year randomized, double-blind, active comparator, superiority trial tested the efficacy of daily oral 0.75μg eldecalcitol versus 1.0μg alfacalcidol for prevention of osteoporotic fractures. 1054 osteoporotic patients 46 to 92years old were randomly assigned 1:1 to receive eldecalcitol (n=528) or alfacalcidol (n=526). Patients were stratified by study site and serum 25-hydroxyvitamin D level. Patients with low serum 25-hydroxyvitamin D levels (<50nmol/L) were Supplemented with 400IU/day vitamin D 3. Primary end point was incident vertebral fractures. Secondary end points included any non-vertebral fractures and change in bone mineral density and bone turnover markers. Compared with the alfacalcidol group, the incidence of vertebral fractures was lower in eldecalcitol group after 36months of treatment (13.4 vs. 17.5%; hazard ratio, 0.74; predefined 90% confidence interval [CI], 0.56-0.97). Eldecalcitol reduced turnover markers and increased bone mineral density more strongly than alfacalcidol. Eldecalcitol reduced the incidence of three major non-vertebral fractures, which was due to a marked reduction in wrist fractures by a post-hoc analysis (1.1 vs. 3.6%; hazard ratio, 0.29; 95% CI, 0.11-0.77). Among the adverse events, the incidence of increase in serum and urinary calcium was higher in the eldecalcitol group, without any difference in glomerular filtration rate between the two groups. Conclusions: Eldecalcitol is more efficacious than alfacalcidol in preventing vertebral and wrist fractures in osteoporotic patients with vitamin D sufficiency, with a safety profile similar to alfacalcidol.

Original languageEnglish
Pages (from-to)605-612
Number of pages8
JournalBone
Volume49
Issue number4
DOIs
Publication statusPublished - 2011 Oct

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Osteoporotic Fractures
Cholecalciferol
Double-Blind Method
Bone Density
Wrist
Incidence
Serum
eldecalcitol
Confidence Intervals
Bone Remodeling
alfacalcidol
Glomerular Filtration Rate
Vitamin D
Calcium
Safety
Bone and Bones

Keywords

  • Active vitamin D
  • Bone mineral density
  • Osteoporosis
  • Vertebral fracture
  • Wrist fracture

ASJC Scopus subject areas

  • Physiology
  • Endocrinology, Diabetes and Metabolism
  • Histology

Cite this

A new active vitamin D3 analog, eldecalcitol, prevents the risk of osteoporotic fractures - A randomized, active comparator, double-blind study. / Matsumoto, Toshio; Ito, Masako; Hayashi, Yasufumi; Hirota, Takako; Tanigawara, Yusuke; Sone, Teruki; Fukunaga, Masao; Shiraki, Masataka; Nakamura, Toshitaka.

In: Bone, Vol. 49, No. 4, 10.2011, p. 605-612.

Research output: Contribution to journalArticle

Matsumoto, Toshio ; Ito, Masako ; Hayashi, Yasufumi ; Hirota, Takako ; Tanigawara, Yusuke ; Sone, Teruki ; Fukunaga, Masao ; Shiraki, Masataka ; Nakamura, Toshitaka. / A new active vitamin D3 analog, eldecalcitol, prevents the risk of osteoporotic fractures - A randomized, active comparator, double-blind study. In: Bone. 2011 ; Vol. 49, No. 4. pp. 605-612.
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AU - Hayashi, Yasufumi

AU - Hirota, Takako

AU - Tanigawara, Yusuke

AU - Sone, Teruki

AU - Fukunaga, Masao

AU - Shiraki, Masataka

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N2 - Background: Eldecalcitol is an analog of 1,25-dihydroxyvitamin D 3 that improves bone mineral density; however, the effect of eldecalcitol on the risk of fractures is unclear. The objective of this study is to examine whether eldecalcitol is superior to alfacalcidol in preventing osteoporotic fractures. This trial is registered with ClinicalTrials.gov, number NCT00144456. Methods and results: This 3year randomized, double-blind, active comparator, superiority trial tested the efficacy of daily oral 0.75μg eldecalcitol versus 1.0μg alfacalcidol for prevention of osteoporotic fractures. 1054 osteoporotic patients 46 to 92years old were randomly assigned 1:1 to receive eldecalcitol (n=528) or alfacalcidol (n=526). Patients were stratified by study site and serum 25-hydroxyvitamin D level. Patients with low serum 25-hydroxyvitamin D levels (<50nmol/L) were Supplemented with 400IU/day vitamin D 3. Primary end point was incident vertebral fractures. Secondary end points included any non-vertebral fractures and change in bone mineral density and bone turnover markers. Compared with the alfacalcidol group, the incidence of vertebral fractures was lower in eldecalcitol group after 36months of treatment (13.4 vs. 17.5%; hazard ratio, 0.74; predefined 90% confidence interval [CI], 0.56-0.97). Eldecalcitol reduced turnover markers and increased bone mineral density more strongly than alfacalcidol. Eldecalcitol reduced the incidence of three major non-vertebral fractures, which was due to a marked reduction in wrist fractures by a post-hoc analysis (1.1 vs. 3.6%; hazard ratio, 0.29; 95% CI, 0.11-0.77). Among the adverse events, the incidence of increase in serum and urinary calcium was higher in the eldecalcitol group, without any difference in glomerular filtration rate between the two groups. Conclusions: Eldecalcitol is more efficacious than alfacalcidol in preventing vertebral and wrist fractures in osteoporotic patients with vitamin D sufficiency, with a safety profile similar to alfacalcidol.

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