Qu Feng Zhi Tong capsule increases mechanical properties of cortical bone in ovariectomised rats

Abstract

Backgroud/objective: Qu Feng Zhi Tong capsule (QF, Buchang Pharma, Xi'an, Shanxi, China) is officially approved Fufang formula in China for the treatment of rheumatoid arthritis (RA). As a Traditional Chinese Medicine formula, it consists of seven herbs, among which Erodium stephanianum, Dipsacus asper, and Viscum Coloratum were reported to be able to prevent bone loss and promote bone healing. Moreover, osthole from Angelica pubescens exerted anabolic effect on cortical bone by activating β-catenin-bone morphogenetic protein (BMP) signalling. So, we hypothesise that the formula QF has beneficial potential on preventing osteoporosis. Method: In this study, high-performance liquid chromatography (HPLC) was used to identify the main constituents in QF, and SD female rats were ovariectomised (OVX) to examine antiosteoporotic efficacy. Thirty OVX rats were orally administrated with QF (162 and 648 ​mg/kg/day, L-QF, and H-QF) or estradiol (1 ​mg/kg/day, E2) for 12 weeks. Sham and OVX control group were treated with vehicle. Results: Eleven compounds in QF extract were identified using HPLC, and the sum of their peak areas was covered 44.2% of total peak area of QF extract. As to in vivo results, compared to OVX group, H-QF had significantly higher ultimate load (P ​< ​0.01) and stiffness (P ​< ​0.01) of diaphysis femur in rats. Micro computed tomography (Micro CT) results showed that both H-QF and L-QF had no effects on the trabecular bone at proximal tibia, while H-QF had significantly more bone volume fraction, cortical bone area fraction, and cortical thickness (P ​< ​0.05), less bone marrow area faction (P ​< ​0.05) and total porosity (P ​< ​0.05) in diaphysis tibia. Further dynamic histomorphometric data demonstrated that H-QF increased percentage of bone formation surface of periosteum （P ​< ​0.001）and decreased percentage of erosion surface of endosteum (P ​< ​0.05). In addition, both of QF groups had no effect on the body weight and uterus endometrial cell height, while estradiol decreased the body weight and increased uterus epithelial significantly. QFs and estradiol groups had higher skeletal muscle weights than those in the OVX group. Conclusion: QF promoted cortical mechanical properties because of its positive effects on cortical thickness, porosity, and skeletal muscle. H-QF increased cortical thickness by promoting bone formation of periosteum and inhibiting bone absorption of endosteum in OVX rats. The translational potential of this article: This study provided theoretical basis for QF as a conventional drug in osteoporosis to enhance cortical bone mechanical and avoid long bone fracture. As cortical diaphyseal bone is an important target of RA, this study also provides a possibility that QF is beneficial to RA by its positive effects on cortical bone to prevent bone erosions in RA patients.

Keywords

• Cortical bone
• Mechanical properties
• Osteoporosis
• Qu Feng Zhi Tong capsule