K2 and D3

In a 2022 meta-analysis and systematic review, Zhou et al¹ investigated the efficacy of vitamin K2 in preventing loss of bone mineral density.  They had a good methodology, with inclusion and exclusion criteria.  They looked at RCTs, and found some significant effects when osteoporotic women took vitamin K2.  Their bone mineral density actually increased.  In addition, they found that vitamin K2 supplementation resulted in a shift to a greater amount of the active carboxylated form of osteocalcin, and a lesser amount of undercarboxylated osteocalcin.  They note that Vitamin K is a cofactor of the enzyme that carboxylates osteocalcin, and when osteocalcin is carboxylated, it is able to help increase bone mineral density.

Despite finding these positive effects on osteocalcin, the authors did not find a significant difference in fractures associated with vitamin K2 supplementation, even though they note that carboxylated  osteocalcin itself has been shown to be associated with a reduced risk of fracture.  They also found that there were some side effects from taking vitamin K2, such as nausea, but nothing severe.  They do say that more study needs to be done.  They would like to see larger, high quality studies, without the bias that they found in some of the studies they looked at. 

One of the studies included in this systematic review was by Ushiroyama et al.²  They used the MK-4 form of vitamin K2 in their intervention, and compared it to vitamin D3 as well as to the combination of K2 with D3, and also placebo.  It took two years before the increase in bone mineral density was seen with vitamin K2, while for those who took both vitamin K2 and vitamin D3, increases in bone mineral density were seen as soon as six months.  The increases were greater in this group, and a greater percentage of the people saw an increase. 

References:

Zhou M, Han S, Zhang W, Wu D. Efficacy and safety of vitamin K2 for postmenopausal women with osteoporosis at a long-term follow-up: meta-analysis and systematic review. Journal of Bone and Mineral Metabolism. June 2022:1-10. 

Ushiroyama T, Ikeda A, Ueki M. Effect of continuous combined therapy with vitamin K2 and vitamin D3 on bone mineral density and coagulofibrinolysis function in postmenopausal women. Maturitas. 2002;41(3):211-221.