Treatment of osteoporosis with eldecalcitol, a new vitamin D analog: a comprehensive review and meta-analysis of randomized clinical trials

Abstract

Objective: Eldecalcitol (ELD) is an active form of vitamin D analog that has been approved for the treatment of osteoporosis in Japan. Over recent years, a number of multicenter, randomized controlled clinical trials have been conducted. Our goal is to comprehensively summarize the results from these studies.

Methods: We searched the databases MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials up to February 28, 2015. Each database was searched using search terms "Eldecalcitol" and "ED-71" and the results were combined. The retrieved data from three independent clinical trials included a total of 1,332 patients with osteoporosis. After the data were pooled from three trials, RevMan software was used to conduct meta-analyses to determine the effects of ELD on bone mineral density (BMD) and bone turnover marker (BTM) type I collagen amino-terminal telopeptide (NTX). Effects of ELD on some of the bone formation and bone resorption parameters, incidence of vertebral fractures at the lower spine, and health-related quality of life (HRQOL) in patients with osteoporosis were also summarized.

Results: With a test for overall effect Z=6.35, ELD could increase lumbar BMD (P<0.00001). In comparison with alphacalcidol, ELD suppressed the NTX level to a greater degree (test for overall effect Z=3.82,P<0.0001). ELD was also found to suppress bone alkaline phosphatase (BALP) by 19% (P<0.01) and osteocalcin by 19% (P<0.01) at the dose of 0.75 μg/day. Compared to alfacalcidol, ELD showed higher potency in suppressing serum BALP (26±9 vs 32±11 U/L,P<0.05) and amino-terminal propeptide of procollagen I (PINP) (42±15 vs 59±23 ng/mL,P<0.05). In addition, ELD was found to be more effective in reducing the incidence of vertebral fractures at the lower spine (P=0.029).

Conclusion: Our meta-analysis showed that ELD was more potent than alphacalcidol in reducing BTM (NTX). Clinical data together suggest that ELD is efficient in treating osteoporosis by increasing lumbar BMD; suppressing BTMs, including NTX, BALP, osteocalcin, and PINP; resulting in the reduction in the incidence of vertebral fractures at the lower spine; and increasing the HRQOL in patients with osteoporosis.

Keywords: BALP; BMD; NTX; PINP.

Figure 1

Flow diagram for study selection. Abbreviation: ELD, eldecalcitol.

Figure 2

Eldecalcitol increases lumbar BMD, as compared with placebo. Abbreviations: SD, standard deviation; CI, confidence interval; BMD, bone mineral density;df, degree of freedom; MD, mean difference; SE, standard error.

Figure 3

Eldecalcitol has no effect on hip BMD, as compared to placebo. Abbreviations: SD, standard deviation; CI, confidence interval; BMD, bone mineral density;df, degree of freedom; MD, mean difference; SE, standard error.

Figure 4

Eldecalcitol suppressed NTX to a greater degree in comparison with alfacalcidol. Abbreviations: SD, standard deviation; CI, confidence interval; NTX, type I collagen amino-terminal telopeptide;df, degree of freedom; MD, mean difference; SE, standard error.