Effects of Vitamin D, K1, and K2 Supplementation on Bone Formation by Osteoblasts In Vitro: A Meta-analysis

Abstract

Bone loss is a major health problem that many aging individuals will face and thus research focusing on enhancing bone formation is of great importance. Cell biology or in vitro studies are particularly useful in exploring the exact effects a vitamin, supplement or drug has on particular processes within a certain cell type. Although there have been many cell biology articles focusing on the effects of vitamin D, K 1 or K 2 addition on bone formation in vitro, there has yet to be a consensus amongst the literature. The purpose of this article is to determine the effects of vitamin D, K 1 and K 2 supplementation on osteoblast maturation parameters through meta-analysis of past cell biology literature. A Hedges d effect size was calculated for each experiment extracted from past literature and the experiments were grouped by experiment and cell type. Homogeneity was assessed by the Cochran's Q test, while the effect sizes' departure from zero was assessed by a 95% confidence interval and a non-directional test. Supplementation with vitamin D, K 1 and K 2 , along with the combination of vitamin K 2 + 1,25-dihydroxyvitamin D, increased bone mineralization, while not consistently affecting all of the other parameters associated with bone formation. Vitamin K 2 and D addition had variable effects on bone formation using different cell types, which calls into question the suitability of particular cell lines as models for clinical trials. Therefore, the conditions and parameters in which bone formation is studied in vitro must be considered carefully before running a vitamin supplementation or drug-testing experiment.

Beneficial Effects of Vitamins K and D3 on Redox Balance of Human Osteoblasts Cultured with Hydroxyapatite-Based Biomaterials

“…The MK-7 homologue is the most effective, either alone or combined with vitamin D3. Enhanced proliferation of MK-7-treated osteoblasts has been confirmed by other authors [72,73]. However, in previous studies, osteoblasts were not cultured in the presence of hydroxyapatite-based biomaterials.…”

PHNQ from Evechinus chloroticus Sea Urchin Supplemented with Calcium Promotes Mineralization in Saos-2 Human Bone Cell Line

“…Vitamin K also comprises a family of naphthoquinones and has been used as a therapy to prevent bone mineral loss and reduce risk of fracture in osteoporotic patients [ 35 ]. Vitamin K 1 has been shown to retard bone loss and improve bone health in human trials [ 35 , 36 , 37 ]. Vitamin K 2 has been demonstrated to have the effect of osteoporosis prevention and has been clinically utilized.…”

Vitamin K2 Modulates Vitamin D‐Induced Mechanical Properties of Human 3D Bone Spheroids In Vitro

“…(51) Vitamins D and K2, as well as the combination of the two, have previously been described to enhance mineralization of osteoblasts in vitro. (52) In clinical studies, combined administration of vitamins D and K is suggested to improve bone quality and lower the risk of fractures. (33) Moreover, a higher gain in BMD has been reported in postmenopausal women with osteoporosis treated with a combination of the vitamins compared with each vitamin alone or calcium.…”

“…( 51 ) Vitamins D and K2, as well as the combination of the two, have previously been described to enhance mineralization of osteoblasts in vitro. ( 52 )…”