Comparison of Efficacy and Safety of Denosumab with Eldecalcitol or Native Vitamin D in Postmenopausal Chinese Women with Osteoporosis (ESCORT): A Randomized Controlled Trial.

Background

Eldecalcitol (ELD) and denosumab are some of the most common therapeutic options for osteoporosis management. ELD effectively increases bone mineral density (BMD) in osteoporotic patients, independent of baseline vitamin D status or calcium intake. However, the efficacy of denosumab combined with either ELD or native vitamin D plus calcium in postmenopausal Chinese women with osteoporosis has not been established.

Methods

In this single-center, randomized, open-label, active-controlled clinical trial, postmenopausal women with osteoporosis (defined as a BMD T-score ≤ -2.5 at the lumbar spine [LS], total hip [TH], or femoral neck [FN], or low bone mass with fragility fracture history) were enrolled from Xi'an Honghui Hospital in China and randomized 1:1 to two 12-month treatment regimens: the ELD group received ELD (0.75 μg orally daily) combined with denosumab (60 mg subcutaneously every 6 months), while the control group received the same denosumab regimen plus native vitamin D (800 IU orally daily) and calcium (600 mg orally daily). The primary endpoint was the 12-month percent change in LS BMD from baseline. Secondary endpoints included changes in FN- and TH-BMD from baseline, bone turnover markers, serum parathyroid hormone, quality of life, and the incidence of new fractures.

Results

Of the 100 randomized participants, 45 in the ELD group and 46 in the control group were included in the efficacy analysis. After 12 months of treatment, LS-BMD increased significantly in both groups (both p < 0.05), with a greater increase in the ELD group than in the control group (6.75% vs. 4.99%), yielding a statistically significant between-group least-squares mean difference of 1.75% (95% CI, 0.10 to 3.41; p = 0.038). The reduction in serum β-CTX was significantly smaller in the ELD group than in the control group at 3 months (91.00% vs. 93.62%, p = 0.002), with no significant between-group differences thereafter. Seven fractures were reported (one non-vertebral in the ELD group; one vertebral and five non-vertebral in the control group). No significant between-group differences in FN- or TH-BMD, quality of life, or overall adverse event rates were observed. Both regimens were generally well-tolerated, without clinically meaningful calcium-related safety signals.

Conclusions

Combination therapy with denosumab and eldecalcitol improved LS-BMD more effectively than denosumab with native vitamin D and calcium in postmenopausal Chinese women with osteoporosis. Clinical trial number: ClinicalTrials.gov identifier NCT05884372, registered on 1 June 2023.