Effects of combined menaquinone-4 and PTH treatment on osetogenesis and angiogenesis in calvarial defect in osteopenic rats.

Purpose: The aim of this study was to evaluate the effect of combining human parathyroid hormone (1-34) (PTH; PTH) and menaquinone-4 (MK-4) on calvarial bone defect repair in osteopenic rats.

Methods: Fourteen week olds were subject to craniotomy for the establishment of osteopenic animal models fed through a chronically low-protein diet. After that, critical calvarial defect model was established and all rats were randomly divided into four groups: sham, MK-4, PTH, and PTH + MK-4. The animals received MK-4 (30 mg/kg/day), PTH (60 μg/kg, three times a week), or PTH (60 μg/kg, three times a week) plus MK-4 (30 mg/kg/day) for 8 weeks, respectively. Serum γ-carboxylated osteocalcin (Gla-OC) levels, histological and immunofluorescent labeling were employed to evaluate the bone formation and mineralization in calvarial bone defect. In addition, Microfil perfusion, immunohistochemical, and micro-CT suggested enhanced angiogenesis and bone formation in calvarial bone healing.

Results: In this study, treatment with either PTH or MK-4 promoted bone formation and vascular formation in calvarial bone defects compared with the sham group. In addition, combined treatment of PTH plus MK-4 increased serum level of Gla-OC, improved vascular number and vascular density, and enhanced bone formation in calvarial bone defect in osteopenic conditions as compared with monotherapy.

Conclusions: In summary, this study indicated that PTH plus MK-4 combination therapy accelerated bone formation and angiogenesis in calvarial bone defects in presence of osteopenia.