Combined treatment with Cinnamaldehyde and β-TCP had an additive effect on bone formation and angiogenesis in critical size calvarial defect in ovariectomized rats

Accumulating evidence suggests that improvements in osteogenesis and angiogenesis play an important role in repairing osteoporotic bone defects. Cinnamomum cassia (C. cassia), a traditional Chinese medicinal herb, is reported to show anabolic effects on osteoblasts. However, whether C. cassia could actually repair bone defects in osteoporotic conditions remains unknown. The purpose of this study was to evaluate the effect of combined treatment with Cinnamaldehyde (main oil isolated from the C. cassia) and beta-tricalcium phosphate (beta-TCP) on bone formation and angiogenesis in critical size calvarial defects in ovariectomized (OVX) rats. Using a previously established OVX model, 5 mm critical size calvarial defect was established in OVX rats. All OVX rats were then randomly divided into OVX group (OVX rats + empty defect), TCP group (OVX rats + beta-TCP), and CTCP group (Cinnamaldehyde 75 mg/kg/day for 12 weeks + beta-TCP). Twelve weeks after treatment, according to Micro-CT and HE staining, combination of Cinnamaldehyde and beta-TCP had an additive effect on bone regeneration compared with other groups (p < 0.05). Based on dynamic fluorochrome-labelling analysis, Cinnamaldehyde + beta-TCP continuously promoted new bone mineralization compared with other groups at each time point (p < 0.05). Microfil perfusion suggested that CTCP group showed more neovascularization compared with other groups (p < 0.05). Immunohistochemical assay supported the findings that Cinnamaldehyde +beta-TCP enhanced expression of OCN, VEGF and CD31. The present study demonstrated that combined treatment with Cinnamaldehyde and beta-TCP promoted bone formation and angiogenesis in osteoporotic bone defects, which provides a promising new strategy for repairing bone defects in osteoporotic conditions.