Abstract: BACKGROUND: Chinese medicine with its good treatment effect and safety is increasingly applied to the treatment of osteoporosis. Bushen Zhuanggu Fang is currently widely used in clinical practice as an agreement of the Affiliated Hospital of Shandong University of Chinese Medicine, and has obtained excellent treatment results. 
OBJECTIVE: To evaluate the effects of Bushen Zhuanggu Fang on bone metabolism and bone density in a rat model of ovariectomized osteoporosis.
METHODS: Sixty Sprague-Dawley rats were randomly grouped into sham group, model group, alendronate sodium group, high-, middle-, and low-dose Bushen Zhuanggu Fang groups (n=10 per group). Rat models of ovariectomized osteoporosis were made in the latter five groups. The sham group received no intervention except for the removal of periovarian adipose tissue. After 8 weeks of modeling, high-, middle- and low-dose Bushen Zhuanggu Fang groups were given 2.34, 1.17, 0.58 g/kg per day, respectively, the alendronate sodium group was given 1 mg/kg per day, and sham operation group and model group were intragastrically given the same volume of normal saline, once a day. The serum levels of alkaline phosphatase, RUNT-related transcription factor 2 and receptor activator of nuclear factor-κB ligand were detected after 12 weeks of continuous gavage. The bone mineral density and microstructure of the right femur were observed. Hematoxylin-eosin staining was used to observe histopathological changes. The expressions of Wnt1 and bone morphogenetic protein 2 were immunohistochemically detected.
RESULTS AND CONCLUSION: Compared with the sham group, the bone mineral density and bone trabecular number of the model group were significantly reduced at 8 weeks after modeling (P < 0.05), indicating the successful modeling. Compared with the model group, the bone mineral density, bone volume ratio, bone surface area/tissue volume ratio, and the number of bone trabeculae were significantly increased, while trabecular separation was significantly reduced in the low-, middle-, and high-dose Bushen Zhuanggu Fang groups and the alendronate sodium group (P < 0.01). Moreover, the alendronate sodium group showed better improvements than the three Bushen Zhuanggu Fang groups. Hematoxylin-eosin staining results showed that compared with the model group, the number and continuity of bone trabeculae were increased in the low-, middle- and high-dose Bushen Zhuanggu Fang groups and alendronate sodium group, indicating that Bushen Zhuanggu Fang could significantly improve the bone microstructure of ovariectomized rats. The serum levels of RUNT-related transcription factor 2 in the low-, middle- and high-dose Bushen Zhuanggu Fang groups and the alendronate sodium group were higher than those in the model group (P < 0.01), while the levels of alkaline phosphatase and receptor activator of nuclear factor-κB ligand were significantly lower than those in the model group (P < 0.01). The alendronate sodium group showed better improvement effects than the three Bushen Zhuanggu Fang groups. Immunohistochemistry results showed that the relative expressions of Wnt1 and bone morphogenetic protein 2 in the femur of rats were significantly increased in the low-, middle- and high-dose Bushen Zhuanggu Fang groups and the alendronate sodium group. To conclude, Bushen Zhuanggu Fang can partially improve bone metabolism imbalance in rats, improve the levels of bone formation-related factors, and thereby improve the imbalance between bone resorption and bone formation.

Key words: Bushen Zhuanggu Fang, ovariectomy, osteoporosis, bone metabolism, bone mineral density, rat