For OSTEOPOROSIS OR OSTEOPENIA, Vitamin K2 is an essential component of bone health, as it activates a protein called osteocalcin, which binds calcium into the bone architecture. It also directs calcium away from arteries and towards bones, away from soft tissues such as arteries, which improves bone mineral density and reduces fracture risk. Vitamin K2 stimulates osteoblasts (our bone-building cells) while reducing the activity and formation of osteoclasts (natural bone-breakdown cells). This helps to maintain a healthier bone balance and prevents excessive bone loss. Clinical studies show that vitamin K2 supplements can slow the rate of bone loss, improve bone quality, and reduce the risk of hip and vertebral fractures in people with osteoporosis.

Our bones naturally remodel themselves continuously, maintaining a balance between creating new bone matrix, with osteoblast cells, and clearing out old bone that is no longer needed, with osteoclasts. Vitamin K2, or menaquinone, promotes osteoblast activity through the carboxylation of proteins called osteocalcin. Osteocalcin must undergo a process called carboxylation to function properly. Vitamin K2 acts as a cofactor for the enzyme gamma-glutamyl carboxylase which performs this carboxylation and modifies the protein; without it, osteocalcin remains in an inactive form and cannot efficiently integrate calcium into the bone structure. In addition, vitamin K2 can promote the formation of new osteoblast cells, by encouraging the proliferation of bone marrow stem cells and stimulating osteoblast differentiation, which are crucial steps in forming new bone structure. Vitamin K2 also protects and prolongs the lifespan of the osteoblasts that create bone.

Active osteocalcin binds with calcium and other minerals, allowing them to be absorbed into the bone matrix. By aiding calcium absorption, vitamin K2 contributes to improved mineralization, and increased bone density and overall bone strength, potentially reducing the risk of fractures.

There is also another protein activated by vitamin K2 called Matrix Gla Protein (MGP). By activating MGP, Vitamin K2 directs calcium towards the skeleton for bone mineralization rather than depositing calcium into arteries and other soft tissues. The presence of calcium in arteries can eventually lead to cardiovascular issues such as coronary artery disease and peripheral vascular disease, so by guiding calcium, vitamin K2 benefits not only bone health, but cardiovascular health as well.

Japanese researchers have been pioneers in the study of vitamin K2 for osteoporosis and for decades, the high-dose menaquinone-4 (MK-4) form of vitamin K2, known as menatetrenone, has been approved as a prescription drug for osteoporosis treatment in Japan. A series of Japanese randomized controlled trials (RCTs) have consistently shown that 45 mg per day of high dose vitamin K2 (MK-4) can significantly reduce the incidence of fractures. A meta-analysis of seven Japanese RCTs involving over 3,000 postmenopausal women found that MK-4 supplementation very significantly reduced the risk of:

• Vertebral fractures by about 60%.
• Hip fractures by about 77%.
• Non-vertebral fractures by about 81%.¹

This is noteworthy because as many as one-third of women and one-fifth of men over the age of 50 will suffer an osteoporotic fracture. And after suffering one fracture, the risk of future fractures increases by 86%!²˒³

While the fracture-reducing effect is the most pronounced finding, some Japanese studies have also demonstrated a positive effect on bone mineral density, particularly in the lumbar spine. For example, a 2-year study found that high-dose vitamin K2 (MK-4) treatment showed a significantly lower incidence of new clinical fractures compared to the control group. While the vitamin K2 group did not show a large increase in BMD, it was able to sustain its lumbar spine BMD, whereas the control group experienced a decline.⁴ This suggests that MK-4 helps to maintain bone mass, even if it does not always lead to a dramatic increase — it may work more on bone quality and strength rather than density alone.

Vitamin K2 also inhibits osteoclast formation, reducing the speed and extent of bone breakdown. Ensuring the proper balance in the bone remodeling cycle, vitamin K2 works by suppressing the activity and formation of osteoclasts, the cells that are responsible for the breakdown and resorption of bone tissue. It does this by inhibiting the pathway of a protein complex called NF-κB which is essential for the formation of osteoclasts, effectively slowing down bone resorption. Vitamin K2 has also been shown to interfere with the RANK/RANKL pathway which is the primary signaling system that tells osteoclast precursors to differentiate and become active. Vitamin K2 effectively reduces the number of osteoclasts and inhibits their ability to break down bone.⁵

A healthy skeleton is in a state of homeostasis, where the rate of bone resorption by osteoclasts is perfectly matched by the rate of bone formation by osteoblasts. This ensures that the skeleton’s structural integrity is maintained and that it can repair itself. Vitamin K2 has a profound effect on homeostasis, specifically by helping to regulate the balance of calcium in your body. Vitamin K2 supplementation is a beneficial strategy for maintaining homeostasis, improving bone health and treating osteoporosis.

While calcium and Vitamin D are foundational for strong bones, Vitamin K2 is a key component in preventing and managing bone loss. It is vital for ensuring that the calcium is directed where it belongs — in your bones. In our clinic, we recommend vitamin K2 to patients at risk for osteoporosis or who already have low bone density. People taking this essential vitamin often experience stabilization of bone loss and at times improvements in bone density.

Recommendation: Vitamin K2 as MK-7, or menaquinone-7, 90 to 180 mcg per day. We prefer it in an oil formula because Vitamin K2 is a fat-soluble vitamin. It is best absorbed when taken with a meal that contains fat or oil such as avocado, salmon, or salad dressing.

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