Inverse correlation between the changes of lumbar bone mineral density and serum undercarboxylated osteocalcin after vitamin K2 (menatetrenone) treatment in children treated with glucocorticoid and alfacalcidol

We have reported that alfacalcidol plus menatetrenone, a vitamin K-2 with four isoprene units (menaquinone-4), treatment is useful for improving bone problems in children with skeletal unloading. The aim of this study was to evaluate the effect of menatetrenone on bone metabolism in long-term glucocorticoid-treated children with alfacalcidol treatment. Twenty children who had been treated with fixed dosages of prednisolone and alfacalcidol (0.03 mug/kg/day) for 24 weeks were enrolled in a prospective pilot study, and assigned to receive alfacalcidol (0.03 mug/kg/day) or alfacalcidol (0.03 mug/kg/day) plus menatetrenone (approximately 2 mg/kg/day). Bone biochemical markers and bone mineral density (BMD) were measured at baseline and after the 12-week treatment. In the group receiving alfacalcidol plus menatetrenone, serum carboxylated osteocalcin (OC) (p = 0.0022) and lumbar BMD (p = 0.0029) increased and serum undercarboxylated OC (p = 0.0004) decreased significantly in comparison to the group receiving alfacalcidol; further, the change of lumbar BMD showed an inverse correlation to the change of serum undercarboxylated OC (r = -0.744, p = 0.0134) and positive correlations to the baseline values of bone turnover markers such as serum levels of intact OC, bone-specific alkaline phosphatase and type I procollagen carboxyl extension peptide and urinary levels of deoxypyridinoline and N-telopeptide of type I collagen. No adverse effect was observed. This is a small short-term study, but its results suggest that menatetrenone effectively and safely increases lumbar BMD probably through carboxylation of OC in long-term prednisolone-treated children with alfacalcidol treatment who have a high bone turnover. Randomized double-blind controlled trials are needed to confirm our findings.