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 When calcifediol treatment was withdrawn in Group A2, 25(OH)D levels decreased to baseline levels (28.5 ± 8.7 ng/mL at month 4 versus 14.4 ± 6.0 ng/mL at month 12).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).

• Authors: José Luis Pérez-Castrillón, Antonio Dueñas-Laita, Carlos Gómez-Alonso, Esteban Jódar, Javier Del Pino-Montes, Maria Luisa Brandi, Fernando Cereto Castro, José Manuel Quesada-Gómez, Laura Gallego López, José Manuel Olmos Martínez, María Rosa Alhambra Expósito, Bernat Galarraga, Jesús González-Macías, José Luis Neyro, Roger Bouillon, Gonzalo Hernández-Herrero, Nieves Fernández-Hernando, Sandra P Chinchilla
• Journal: Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research (J Bone Miner Res) Vol. 38 Issue 4 Pg. 471-479 (04 2023) ISSN: 1523-4681 [Electronic] United States
• PMID: 36661855 (Publication Type: Randomized Controlled Trial, Multicenter Study, Clinical Trial, Phase III, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 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).

Chemical References

• Calcifediol
• Vitamin D
• Cholecalciferol

Topics

• Humans
• Female
• Calcifediol
• Postmenopause
• Vitamin D
• Cholecalciferol (adverse effects)
• Vitamin D Deficiency (drug therapy)
• Dietary Supplements
• Double-Blind Method