title: 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.
abstract: We have reported that alfacalcidol plus menatetrenone, a vitamin K2 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 microg/kg/day) for 24 weeks were enrolled in a prospective pilot study, and assigned to receive alfacalcidol (0.03 microg/kg/day) or alfacalcidol (0.03 microg/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.
authors.affiliation: Department of Pediatrics, Yamaguchi University School of Medicine, Ube, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Inoue
authors.forename: T
authors.initials: T
authors.lastname: Sugiyama
authors.forename: T
authors.initials: T
authors.lastname: Matsubara
authors.forename: S
authors.initials: S
authors.lastname: Kawai
authors.forename: S
authors.initials: S
authors.lastname: Furukawa
mesh_terms: D000293:Adolescent; D015519:Bone Density / Q000187:drug effects; D002648:Child; D002675:Child, Preschool; D005260:Female; D005938:Glucocorticoids / Q000009:adverse effects* / Q000627:therapeutic use; D006801:Humans; D006887:Hydroxycholecalciferols / Q000627:therapeutic use*; D008159:Lumbar Vertebrae; D008297:Male; D015675:Osteocalcin / Q000097:blood* / Q000737:chemistry; D010024:Osteoporosis / Q000139:chemically induced; D011239:Prednisolone / Q000009:adverse effects / Q000627:therapeutic use; D011446:Prospective Studies; D014812:Vitamin K / Q000031:analogs & derivatives / Q000097:blood / Q000627:therapeutic use*; D024482:Vitamin K 2 / Q000031:analogs & derivatives
chemical_list: D005938:Glucocorticoids; D006887:Hydroxycholecalciferols; D015675:Osteocalcin; D024482:Vitamin K 2; D014812:Vitamin K; C030814:menatetrenone; D011239:Prednisolone; C008088:alfacalcidol