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

The objective of the present review was to summa‑ rize 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 toco‑ trienols), K₂ (menaquinones 4 and 7) and c have also been shown to promote osteoblast development through bone morphoge‑ netic 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, respec‑ tively. Certain vitamins significantly reduce receptor activator of nuclear factor kappa‑B ligand (RANKL) production and RANKL/RANK signaling, while increasing the level of osteo‑ protegerin (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.