Research on the mechanism of Bushen Jianpi decoction (BJD) for preventing and treating osteoporosis caused by aromatase inhibitors (AI) during treatment for breast cancer resection. An ovariectomized mouse model was established using random division into 6 groups: a sham ovariectomized group, a blank control group, a control group, an alendronate group, a BJD group, and a drug combination group. Mice breast cancer cell lines (4T1) were cultured and seeded into the armpits of 6 groups of BALB/c mice. The mouse breast cancer postoperative model was built when resecting the tumor after 3 weeks following seeding tumor. After 1 weeks, the 6 groups of mice were given different drugs. Then the following analyses were made: estradiol (E2) levels and alkaline phosphatase (ALP) levels in the serum; detection of in vitro bone density and calcium and bone phosphorus content; tumor pathology and immunohistochemistry detection. The results suggested that BJD decreased levels of ALP in ovariectomized mice, and there was a trend for improved bone loss. BJD strengthened the trend of alendronate to improve bone loss, improved bone density, bone calcium and phosphorous, and reduced ALP. BJD had a certain role on the promotion of the expression of estrogen receptors (ERs) in the relapse of the tumor tissue. Combined therapy with BJD and alendronate can act synergistically against osteoporosis, which was possibly related to a reduced bone conversion rate through inhibiting bone resorption. BJD may block the MAPK signal pathway in breast cancer cells, increasing the expression of ERs and making cancer cells sensitive to endocrine treatment.