The Dual Role of Vitamin K2 in “Bone-Vascular Crosstalk”: Opposite Effects on Bone Loss and Vascular Calcification

Abstract

Osteoporosis (OP) and vascular calcification (VC) represent relevant health problems that frequently coexist in the elderly population. Traditionally, they have been considered independent processes, and mainly age-related. However, an increasing number of studies have reported their possible direct correlation, commonly defined as “bone-vascular crosstalk”. Vitamin K2 (VitK2), a family of several natural isoforms also known as menaquinones (MK), has recently received particular attention for its role in maintaining calcium homeostasis. In particular, VitK2 deficiency seems to be responsible of the so-called “calcium paradox” phenomenon, characterized by low calcium deposition in the bone and its accumulation in the vessel wall. Since these events may have important clinical consequences, and the role of VitK2 in bone-vascular crosstalk has only partially been explained, this review focuses on its effects on the bone and vascular system by providing a more recent literature update. Overall, the findings reported here propose the VitK2 family as natural bioactive molecules that could be able to play an important role in the prevention of bone loss and vascular calcification, thus encouraging further in-depth studies to achieve its use as a dietary food supplement.

Three-Dimensional Co-Culture System of Human Osteoblasts and Osteoclast Precursors from Osteoporotic Patients as an Innovative Model to Study the Role of Nutrients: Focus on Vitamin K2

“…In addition, serum levels of BTMs were measured: bALP, PINP, PICP, and OC are deemed important bone formation markers [ 50 ]. In particular, OC exists in two circulating forms [ 8 ]: undercarboxylated (unOC), used as a bone formation marker because it does not bind hydroxyapatite, and carboxylated (cOC), which, instead, binds bone mineralized matrix [ 22 ]. Since total OC is considered a non-specific indicator of bone activity and, therefore, must be interpreted with attention, we measured both circulating forms and their ratio (cOC/unOC) as a predictor of bone formation.…”

“…Nutrients 2021, 13, 2823 2 of 17 Among all possible osteo-protective compounds, vitamin K2 is noteworthy [6], a family of different isoforms, known as menaquinones (MKs), which differ from each other by the number of isoprenoid units in the side chain (n = 1-14), and in the last few years, they have received attention for their positive effects in bone metabolism [7][8][9][10][11]. Although its beneficial role in decreasing bone loss and risk of osteoporotic fractures has been established [12][13][14][15], additional studies are needed to deeply understand if vitamin K2 intake would provide a valid support to prevent and treat osteoporosis or if some people may be refractory to its effects.…”

The Impact of Vitamin K2 (Menaquionones) in Children’s Health and Diseases: A Review of the Literature

“…In recent decades, vitamin K2 (menaquinone) has been specifically highlighted as a crucial cardiovascular and bone health nutrient [ 74 ].…”

COVID-19 Mortality Risk Correlates Inversely with Vitamin D3 Status, and a Mortality Rate Close to Zero Could Theoretically Be Achieved at 50 ng/mL 25(OH)D3: Results of a Systematic Review and Meta-Analysis

“…Even when calcium blood levels are high, the culprit for undesirable vascular calcification is not vitamin D but insufficient blood levels of vitamin K2. Thus, daily vitamin D3 supplementation in the range of 4000 to 10,000 units (100 to 250 µg) needed to generate an optimal vitamin D3 blood level in the range of 40–60 ng/mL has been shown to be completely safe when combined with approximately 200 µg/mL vitamin K2 [ 80 , 81 , 82 ]. However, this knowledge is still not widespread in the medical community, and obsolete warnings about the risks of vitamin D3 overdoses unfortunately are still commonly circulating.…”