Vitamin K ₂ improves renal function and increases femoral bone strength in rats with renal insufficiency

Renal insufficiency induces cortical bone loss in rats. The present study examined the influence of vitamin K ₂ on renal function, cortical bone mass, and bone strength in rats with renal insufficiency. Thirty male Sprague-Dawley rats (8 weeks old) were randomized by the stratified weight method to the following three groups of 10 animals each: sham operation (control), 5/6 nephrectomy, and 5/6 nephrectomy + oral vitamin K ₂ (menaquinone-4, menatetrenone, 30 mg/kg, 5 days/week). Treatment was initiated 10 days after surgery. After 6 weeks of treatment, samples of serum, urine, and bone (femur and tibia) were obtained. Renal function was evaluated, bone histomorphometric analysis was performed on the tibial diaphysis, and the bone mineral density (BMD) and mechanical strength of the femoral diaphysis were determined by peripheral quantitative computed tomography and a three-point bending test, respectively. Nephrectomy induced renal dysfunction, as indicated by increased levels of serum creatinine and urea nitrogen along with a decrease of creatinine clearance; and it also decreased BMD without significantly affecting bone strength at the femoral diaphysis. Vitamin K ₂ improved renal function parameters but did not significantly influence BMD at the femoral diaphysis. However, vitamin K ₂ decreased the bone marrow area of the tibial diaphysis and increased the stiffness of the femoral diaphysis. These findings suggest that administration of vitamin K ₂ improves renal function and increases cortical bone strength without altering BMD in rats with renal insufficiency.