Bone protection mechanism of Zuogui Pill in an osteoporosis model of breast cancer rats after endocrine therapy

Background: Postmenopausal breast cancer patients treated with aromatase inhibitors (AIs) have an increased risk of developing secondary osteoporosis. Zuogui Pill has been proven to have obvious preventative and therapeutic effects against osteoporosis in the clinic. However, the possible mechanism of this bone-protective mechanism of Zuogui Pill is still largely unknown. Methods: An osteoporosis model of postmenopausal breast cancer was generated by gavage of letrozole in ovariectomized mice with breast cancer. Serum oestradiol (E2), bone alkaline phosphatase (BALP), and amino terminal propeptide of type Ⅰ collagen (PINP) were detected by enzyme-related immunosorbent assays (ELISAs). After death, the right femur and tibia were taken and stained with HE to observe the bone histopathology. Microcomputed tomography (µCT) was used to detect bone density and trabecular microstructure in vitro. The protein expression levels of Wnt3a, β-catenin and Runx2 in bone tissue were detected by Western blots. Results: Zuogui Pill significantly decreased the serum level of bone alkaline phosphatase (BALP) and the level of amino terminal procollagen Ⅰ propeptide (PINP) but had no significant effect on oestradiol (E2). Zuogui Pill improved bone tissue morphology, bone microstructure and bone mineral density. The protein expression levels of Wnt3a, β-catenin and Runx2 in the Zuogui Pill groups were significantly increased. Conclusion: Zuogui Pill exerts a bone-protective effect through the Wnt/β-catenin and Wnt/Runx2 pathways and has good application value for the treatment of osteoporosis.