Liu Minying, Liu Chongshan, Cevallos Nicolas, Orbach Benjamin N, Hernandez Christopher J, Fu Xueyan, Lee Jennifer, Booth Sarah L, Shea M Kyla
USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA 02111, United States.
Orthopaedic Surgery, University of California, San Francisco, CA 94143, United States.
JBMR Plus. 2025 Apr 10;9(6):ziaf059. doi: 10.1093/jbmrpl/ziaf059. eCollection 2025 Jun.
Vitamin K has been implicated in skeletal health because vitamin K-dependent proteins are present in bone tissue. While there are multiple forms of vitamin K, most research has focused on phylloquinone, which is found mainly in plant-based foods, and its metabolite menaquinone-4 (MK4). However, there are additional forms of vitamin K that are bacterially produced that appear to influence bone health but have not yet been studied extensively. Herein, we evaluated the effects of menaquinone-9 (MK9), a bacterially produced form of vitamin K, on bone tissue quality and density in young mice. Four-week-old male ( = 32) and female ( = 32) C57BL/6 mice were supplemented with 0.06 mg/kg diet or 2.1 mg/kg diet of MK9 for 12 wk. During week 11, a subgroup of mice ( = 7/sex/group) received daily deuterium-labeled MK9 to trace its metabolic fate in bone. Liver MK4 and MK9 were significantly higher in mice fed 2.1 mg MK9/kg compared to those receiving 0.06 mg MK9/kg, regardless of sex (all ≤ .017). MK4 was the only vitamin K form detected in bone, with 63%-67% of skeletal MK4 in mice fed 2.1 mg MK9/kg derived from deuterium-labeled MK9. Femoral tissue strength, maximum bending moment, section modulus, and BMD did not differ significantly between diet groups in either sex (all ≥ .083). Cross-sectional area ( = .003) and moment of inertia ( = .001) were lower in female mice receiving 2.1 mg MK9/kg compared to those receiving 0.06 mg MK9/kg, but no differences were found in male mice. Higher bone MK4 concentrations did not correlate with higher bone tissue quality or density. Despite dietary MK9 being a dietary precursor to MK4 in bone, dietary MK9 supplementation did not affect bone tissue quality or BMD during skeletal development.
维生素K与骨骼健康有关，因为骨组织中存在维生素K依赖蛋白。虽然维生素K有多种形式，但大多数研究集中在主要存在于植物性食物中的叶绿醌及其代谢物甲萘醌-4（MK4）。然而，还有其他由细菌产生的维生素K形式，似乎会影响骨骼健康，但尚未得到广泛研究。在此，我们评估了细菌产生的维生素K形式甲萘醌-9（MK9）对年轻小鼠骨组织质量和密度的影响。将四周龄雄性（n = 32）和雌性（n = 32）C57BL/6小鼠分别用0.06 mg/kg饮食或2.1 mg/kg饮食的MK9补充12周。在第11周，一组小鼠（每组7只/性别）每天接受氘标记的MK9以追踪其在骨骼中的代谢命运。无论性别如何，与接受0.06 mg MK9/kg的小鼠相比，喂食2.1 mg MK9/kg的小鼠肝脏中的MK4和MK9显著更高（所有P≤0.017）。MK4是在骨骼中检测到的唯一维生素K形式，喂食2.1 mg MK9/kg的小鼠骨骼中63%-67%的MK4来自氘标记的MK9。饮食组中，无论雄性还是雌性，股骨组织强度、最大弯矩、截面模量和骨密度均无显著差异（所有P≥0.083）。与接受0.06 mg MK9/kg的雌性小鼠相比，接受2.1 mg MK9/kg的雌性小鼠的横截面积（P = 0.003）和惯性矩（P = 0.001）较低，但在雄性小鼠中未发现差异。较高的骨骼MK4浓度与较高的骨组织质量或密度无关。尽管饮食中的MK9是骨骼中MK4的饮食前体，但在骨骼发育过程中，饮食补充MK9并不影响骨组织质量或骨密度。
