MAASTRICHT, The Netherlands—Three years of dietary supplementation with vitamin K₂ (MK-4, menatretrenone) maintained bone strength and structure even though bone mineral density (BMD) was not affected, Dutch researchers report in Osteoporosis International.¹ Women assigned to placebo in this randomized, double-blind study continued to lose bone strength, as measured using indices including dual x-ray absorptiometry (DXA), through the period of study.

"In this paper we demonstrate that the main effect of vitamin K₂ on bone in the hip is an increase of the femoral neck BMC [bone mineral content] and width, resulting in maintenance of the calculated bone strength even at decreasing DXA-BMD after the menopause," lead author Marjo H. J. Knapen, PhD, reports. "This makes K₂ an interesting compound for combination therapy with other food supplements (calcium, vitamin D) or drugs (bisphosphonates) with known effects on also DXA-BMD." Dr. Knapen is with the department of biochemistry at the University of Maastricht, in The Netherlands.

Study shows effect of vitamin K₂ on BMC, femoral neck width

This study showed that vitamin K₂ helps maintain bone strength at the femoral neck in postmenopausal women by improving their BMC and femoral neck width (FNW) despite having little effect on BMD.

Dr. Knapen and colleagues undertook this research to resolve some previously conflicting findings in this area, such as measurement of vitamin K₁ as the marker for bone vitamin K status, and reliance on DXA-BMD as a surrogate marker for bone strength. "A disadvantage of this technique is that it gives the amount of calcium per area but does not take into account the three dimensions of the bone," the investigators point out. Dietary vitamin K occurs in different forms [Table 1], and the various menaquinones collectively known as vitamin K₂ might be more important in terms of bone health.

"Although in western society K₂ forms only 10% to 20% of the total vitamin K intake, it is absorbed from the food matrix much better than K1 and may cover 50% of the total vitamin K absorbed. Moreover, it has been demonstrated that vitamin K₂ rather than K₁ is preferentially taken up by extrahepatic tissues such as bone and arteries," the authors write.

Table 1: Dietary Vitamin K

 

Form	Dietary Origin	Total Vit K Intake (%)	Total Absorbed Vit K (%)	Preferentially Taken Up by Bone
Vit K1 (phylloquinone)	Leafy green vegetables	80-90	50	No
Vit K2 (menaquinones)	Fermented foods (cheese, fermented soy beans)	10-20	50	Yes

 

Source: Adapted from Knapen et al.¹

Interest continues to shift away from simple DXA-BMD measurement toward a more sophisticated appreciation of bone geometry for judging bone strength. Knapen et al took this into account. "Although DXA-BMD is still the determinant most generally used in the clinical evaluation of hip fracture risk, it has been stipulated that its uncritical use may lead to size-related artifacts in the estimation of bone strength and in the identification of fracture risk.... [T]he ultimate concern in studying bone status is bone strength. Holding other variables constant, strength will increase both as bone mass increases and as bone size increases," Dr. Knapen notes. To compensate for this, the researchers based densitometric comparisons between groups on BMC as well as on DXA-BMD and used the hip axis length (HAL) and FNW as independent determinants for bone strength. These factors were combined in an equation that also took into account height and body weight.

The study included postmenopausal women ages 55 to 75 with no history of metabolic bone disease, recent fracture, low bone density, ovariectomy, hysterectomy, oral anticoagulant treatment, hormone therapy, or bisphosphonate treatment. Also subjects were not to have used calcitonin, prednisone, heparin, or vitamin K-containing vitamin concentrates or food supplements. The researchers randomized 325 women to receive either a placebo or vitamin K₂ (45 mg/day) for 3 years.

The analysis showed that vitamin K₂ supplementation did not affect DXA-BMD. However, BMC and FNW both increased relative to the placebo group. The women in the vitamin K₂ group also maintained hip bone strength over the 3-year period, while hip bones in the placebo group weakened significantly [Table 2].

Table 2: Effect of Vitamin K₂ Treatment on Bone Strength

 

Bone Strength Parameter Indices	Mean Difference, Vit K2 vs Placebo (%)	P
Compression strength	+2.03	.008
Bending strength	+3.83	.001
Impact strength	+1.72	.03

 

Source: Adapted from Knapen et al.¹

This beneficial effect was greater than previously observed with vitamin K₁, and the researchers think that is partly due to the aliphatic side chain that differentiates K₁ from K₂. Human studies have shown that K₁ and K₂ are both transported to the liver via triglycerides, but only K₂ vitamins are incorporated into low-density lipoproteins for transport to tissues outside the liver. "In that perspective, K₂ seems to be the most logical choice for supplementation because notably bone and arteries (and not the liver) were reported to have a suboptimal vitamin K status in the majority of the healthy population," the investigators conclude. They urge cost-benefit studies of providing supplemental low-dose vitamin K₂ to all postmenopausal women.

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