Abstract
The aim of this study was to determine the skeletal effect of total ethanolic extract from the stem-bark of Ulmus davidiana (UDE) in a rat model of postmenopausal bone loss. Effective dose of UDE was determined in adult female Sprague-Dawley (SD) rats by measuring bone regeneration at fracture site. UDE (250 mg/kg p.o.) was administered to ovariectomized (OVX) osteopenic SD rats for 12 weeks. OVX rats treated with vehicle or 17β-estradiol, and sham-operated rats treated with vehicle served as various controls. Bone mineral density (BMD), microarchitecture, biomechanical strength, turnover markers, and uterotrophic effect were studied. Bioactive markers in UDE were analyzed by HPLC. Human osteoblasts was used to study the effect of compounds on differentiation by alkaline phosphase assay. One-way ANOVA was used to test significance of effects. OVX+UDE group showed BMD, microarchitectural parameters and compressive strength at lumbar vertebra (L5) comparable to sham. At proximal femur, OVX+UDE group exhibited significantly higher BMD, better microarchitecture and compressive strength compared with OVX+vehicle. OVX-induced decrease in Ca/P ratio was completely restored at both skeletal sites by UDE treatment. Serum procollagen N-terminal propeptide and carboxy-terminal collagen crosslinks were respectively higher and lower in OVX+UDE group compared with OVX+vehicle group. Osteogenic genes were upregulated in L5 and anti-resorptive genes were suppressed in proximal femur of OVX+UDE group compared with OVX+vehicle. UDE had no uterine estrogenicity. Analysis of markers yielded two osteogenic isoforms of catechin. In conclusion, UDE completely restored vertebral trabecular bones and strength in osteopenic rats by an osteogenic mechanism and prevented bone loss at proximal femur.