Long-Term Treatment and Effect of Discontinuation of Calcifediol in Postmenopausal Women with Vitamin D Deficiency: A Randomized Trial

Abstract

Vitamin D plays a major role in bone health and probably also in multiple extraskeletal acute and chronic diseases. Although supplementation with calcifediol, a vitamin D metabolite, has demonstrated efficacy and safety in short‐term clinical trials, its effects after long‐term monthly administration have been studied less extensively. This report describes the results of a 1‐year, phase III‐IV, double‐blind, randomized, controlled, parallel, multicenter superiority clinical trial to assess the efficacy and safety of monthly calcifediol 0.266 mg versus cholecalciferol 25,000 IU (0.625 mg) in postmenopausal women with vitamin D deficiency (25(OH)D < 20 ng/mL). A total of 303 women were randomized and 298 evaluated. Patients were randomized 1:1:1 to calcifediol 0.266 mg/month for 12 months (Group A1), calcifediol 0.266 mg/month for 4 months followed by placebo for 8 months (Group A2), and cholecalciferol 25,000 IU/month (0.625 mg/month) for 12 months (Group B). By month 4, stable 25(OH)D levels were documented with both calcifediol and cholecalciferol (intention‐to‐treat population): 26.8 ± 8.5 ng/mL (Group A1) and 23.1 ± 5.4 ng/mL (Group B). By month 12, 25(OH)D levels were 23.9 ± 8.0 ng/mL (Group A1) and 22.4 ± 5.5 ng/mL (Group B). When calcifediol treatment was withdrawn in Group A2, 25(OH)D levels decreased to baseline levels (28.5 ± 8.7 ng/mL at month 4 versus 14.4 ± 6.0 ng/mL at month 12). No relevant treatment‐related safety issues were reported in any of the groups. The results confirm that long‐term treatment with monthly calcifediol in vitamin D‐deficient patients is effective and safe. The withdrawal of treatment leads to a pronounced decrease of 25(OH)D levels. Calcifediol presented a faster onset of action compared to monthly cholecalciferol. Long‐term treatment produces stable and sustained 25(OH)D concentrations with no associated safety concerns. © 2023 Faes Farma SA. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Calcifediol Cornerstone of the Vitamin D Endocrine System

“…Calcifediol may well be an alternative to the use of vitamin D supplementation [ 14 , 15 ]. Calcifediol is absorbed by intestinal cells, transported through the portal vein and is, therefore, immediately accessible to the circulation; meanwhile, native vitamin D is transported more slowly by chylomicrons via the lymphatic system.…”

“…This potency is 6–8 times higher than vitamin D when the baseline serum 25OHD is higher or when large doses are compared [ 17 ]. Thus, clinical trials comparing the efficacy and safety of calcifediol and cholecalciferol in vitamin-deficient situations in the short and long term have reported that calcifediol is more effective; indeed, it sees a more rapid onset of action compared to the monthly administration of cholecalciferol, and possesses no associated safety concerns [ 14 , 15 ]. Long-term calcifediol treatment produces stable and sustained 25 (OH) D concentrations; however, as with “vitamin” D, the withdrawal of treatment leads to a steep decline in 25 (OH) D levels compared to pre-treatment levels [ 15 , 18 ].…”

“…Thus, clinical trials comparing the efficacy and safety of calcifediol and cholecalciferol in vitamin-deficient situations in the short and long term have reported that calcifediol is more effective; indeed, it sees a more rapid onset of action compared to the monthly administration of cholecalciferol, and possesses no associated safety concerns [14,15]. Long-term calcifediol treatment produces stable and sustained 25 (OH) D concentrations; however, as with "vitamin" D, the withdrawal of treatment leads to a steep decline in 25 (OH) D levels compared to pre-treatment levels [15,18]. This Special Issue "Vitamin D Endocrine System: Calcifediol for Treatment and Prevention of Infection and Disease" defines some guidelines for understanding calcifediol as a cornerstone of the vitamin D system and its (potentially) great utility in case of de-ficiency.…”

Exploring a Novel Machine Learning Approach for Evaluating Parkinson's Disease, Duration, and Vitamin D Level

“…2) Decision tree: The decision tree is a method for supervised learning that can effectively address classification and regression problems, primarily in solving classification tasks [18]. The terminology implies its utilization of a tree-like diagram to present predictions derived from a sequence of feature-driven divisions.…”

“…(3) where, y represents the predicted output, b0 represents the bias or intercept term, and b1 represents the single input value (x) coefficient. Each input data column contains a b coefficient (a constant real value) that must be learned from your training data [18].…”