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Summary Eldecalcitol (ELD) is a new oral analog of the active form of vitamin D with anti-resorptive properties. We conducted a meta-analysis to investigate the efficacy and safety of ELD in osteoporosis. Compared with alfacalcidol, ELD significantly lowered vertebral facture risk, increased bone mineral density, but also had a higher risk of hypercalciuria. Purpose This study aimed to investigate the efficacy and safety of eldecalcitol (ELD) in osteoporosis by examining fracture rates, bone mineral density (BMD), bone turnover markers, and adverse events as outcomes. Methods PubMed, EMBASE, and Cochrane Library were searched up to July 20, 2020, to identify eligible randomized controlled trials. The odds ratio (OR) or weighted mean difference (WMD) with 95% confidence interval was calculated by the random-effects model. Results ELD significantly increased lumbar BMD (WMD: 2.80; 95% CI: 1.60, 4.00; P < 0.001, 2 studies involved), total hip BMD (WMD: 2.11; 95% CI: 0.68, 3.55; P = 0.004, 2 studies involved), and femoral neck BMD (WMD: 1.78; 95% CI: 0.76, 2.79; P = 0.001, 1 study involved) compared with alfacalcidol. Moreover, ELD caused a significantly lower rate of vertebral fracture (OR: 0.52; 95% CI: 0.29–0.95; P = 0.034, 2 studies involved) than alfacalcidol, but did not lower the rate of non-vertebral facture (OR: 0.44; 95% CI: 0.06–3.05; P = 0.405, 2 studies involved) compared with alfacalcidol. ELD significantly reduced the percentage change in bone-specific alkaline phosphatase (WMD: − 15.40; 95% CI: − 20.30, − 10.60; P < 0.001, 1 study involved) and serum type I collagen C-telopeptide (WMD: − 38.50; 95% CI: − 50.00, − 27.10; P < 0.001, 1 study involved) as compared with alfacalcidol. ELD was also associated with higher risk of hypercalciuria compared with alfacalcidol (OR: 1.64; 95% CI: 1.22, 2.20; P = 0.001, 2 studies involved). Conclusions This systematic review indicated that ELD was superior than alfacalcidol for improving vertebral fracture risk and BMD. Further large-scale trials should be conducted to verify the long-term effects and safety of ELD in osteoporosis. Prospero registration number CRD42020147518.

Elderly male patients are susceptible to develop osteoporosis and sarcopenia, especially those with fragility fractures, hypogonadism, and prostate cancer with androgen deprivation therapy. However, at present, very few treatments are available for men with sarcopenia. Previous preclinical studies in ovariectomized rats have shown the promising effects of eldecalcitol in ameliorating the bone strength and muscle atrophy. We thus investigated the effects of eldecalcitol on androgen-deficient male mice. Six-week-old male mice underwent orchiectomy (ORX) or sham surgery. Mice were randomly divided into 4 groups (n = 12/per group), including 1) sham mice, 2) ORX group, 3) ORX eldecalcitol 30 ng/kg, and 4) ORX eldecalcitol 50 ng/kg. Eldecalcitol increased bone mass and strength of femur in ORX mice. Eldecalcitol 30 ng/kg dose completely rescued ORX-induced muscle weakness. The RT-qPCR showed that eldecalcitol enhanced the mRNA levels of type I and IIa fibers. The expression levels of MuRF1 and Atrogin-1 of gastrocnemius in the eldecalcitol groups were much lower than that of the ORX group. It is assumed that eldecalcitol potentially acts via PI3K/AKT/FOXOs signaling pathway. These findings provide evidence for evaluating eldecalcitol as an investigational treatment for male patients with sarcopenia and osteoporosis.