Role of vitamins beyond vitamin D<sub>3</sub> in bone health and osteoporosis (Review)

Skalny,Anatoly V.; Aschner,Michael; Tsatsakis,Aristidis; Rocha,Joao B.T.; Santamaria,Abel; Spandidos,Demetrios A.; Martins,Airton C.; Lu,Rongzhu; Korobeinikova,Tatiana V.; Chen,Wen; Chang,Jung-Su; Chao,Jane C.J.; Li,Chong; Tinkov,Alexey A.

doi:10.3892/ijmm.2023.5333

January-2024 Volume 53 Issue 1

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January-2024 Volume 53 Issue 1

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Review Open Access

Role of vitamins beyond vitamin D₃ in bone health and osteoporosis (Review)

Authors:
- Anatoly V. Skalny
- Michael Aschner
- Aristidis Tsatsakis
- Joao B.T. Rocha
- Abel Santamaria
- Demetrios A. Spandidos
- Airton C. Martins
- Rongzhu Lu
- Tatiana V. Korobeinikova
- Wen Chen
- Jung-Su Chang
- Jane C.J. Chao
- Chong Li
- Alexey A. Tinkov
View Affiliations / Copyright

Affiliations: Department of Medical Elementology, Peoples' Friendship University of Russia (RUDN University), Moscow 117198, Russia, Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY 10461, USA, Laboratory of Toxicology and Forensic Sciences, Division of Morphology, Medical School, University of Crete, 70013 Heraklion, Greece, Department of Biochemistry and Molecular Biology, CCNE, Federal University of Santa Maria, Santa Maria, RS 97105‑900, Brazil, Faculty of Science, National Autonomous University of Mexico, Mexico City 04510, Mexico, Laboratory of Clinical Virology, Medical School, University of Crete, 70013 Heraklion, Greece, Department of Preventive Medicine and Public Health Laboratory Science, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, P.R. China, Department of Toxicology, School of Public Health, Sun Yat‑Sen University, Guangzhou, Guangdong 510080, P.R. China, College of Nutrition, Taipei Medical University, Taipei 110, Taiwan, R.O.C., Department of Orthopedics, Affiliated Kunshan Hospital of Jiangsu University, Suzhou, Jiangsu 215300, P.R. China

Copyright: © Skalny et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
Article Number: 9
|
Published online on: December 5, 2023

https://doi.org/10.3892/ijmm.2023.5333
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Abstract

The objective of the present review was to summarize the molecular mechanisms associated with the effects of the vitamins A, C, E and K, and group B vitamins on bone and their potential roles in the development of osteoporosis. Epidemiological findings have demonstrated an association between vitamin deficiency and a higher risk of developing osteoporosis; vitamins are positively related to bone health upon their intake at the physiological range. Excessive vitamin intake can also adversely affect bone formation, as clearly demonstrated for vitamin A. Vitamins E (tocopherols and tocotrienols), K2 (menaquinones 4 and 7) and C have also been shown to promote osteoblast development through bone morphogenetic protein (BMP)/Smad and Wnt/β‑catenin signaling, as well as the TGFβ/Smad pathway (α‑tocopherol). Vitamin A metabolite (all‑trans retinoic acid) exerts both inhibitory and stimulatory effects on BMP‑ and Wnt/β‑catenin‑mediated osteogenesis at the nanomolar and micromolar range, respectively. Certain vitamins significantly reduce receptor activator of nuclear factor kappa‑B ligand (RANKL) production and RANKL/RANK signaling, while increasing the level of osteoprotegerin (OPG), thus reducing the RANKL/OPG ratio and exerting anti‑osteoclastogenic effects. Ascorbic acid can both promote and inhibit RANKL signaling, being essential for osteoclastogenesis. Vitamin K2 has also been shown to prevent vascular calcification by activating matrix Gla protein through its carboxylation. Therefore, the maintenance of a physiological intake of vitamins should be considered as a nutritional strategy for the prevention of osteoporosis.

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