RESUMO
BACKGROUND: Osteoporosis is a systemic skeletal disease of fragility fractures due to the loss of mass and deterioration of the microarchitecture of bone. PURPOSE: The aim of the study was to assess the osteogenic effects and the underlying mechanisms of the combined administration of You-Gui Yin (YGY) and Raloxifene hydrochloride (RLX) in ovariectomized (OVX) mice. METHODS: First, a classic animal model was used to mimic postmenopausal osteoporosis through the removal of the ovary of mice. Second, the OVX mice were administered YGY, RLX, and YGYâ¯+â¯RLX for 12 weeks. Next, the bone microtomographic histomorphometry and bone mineral density (BMD) were assessed by micro-CT, and the biochemical markers of procollagen type I N-terminal propeptide (P1NP) and beta-isomerized C-telopeptide (ß-CTX) in serum were assessed. Finally, primary bone marrow stromal cells (BMSCs) were isolated from the tibia and cultured to evaluate cell proliferation and osteogenic differentiation. RESULTS: The results showed that BMD on the YGYâ¯+â¯RLX group was higher than that on the RLX group (pâ¯<â¯0.05) and did not have a significant difference when compared with the sham group. Notably, the YGYâ¯+â¯RLX group had a dramatically increased trabecular number (Tb.N) compared with that of the YGY group (pâ¯<â¯0.05). Moreover, the BV/TV (bone volume/total volume) and Tb.N in the YGYâ¯+â¯RLX group were higher than that in the RLX group (pâ¯<â¯0.05), and the Tb.Sp (trabecular separation) was lower than that in the RLX group (pâ¯<â¯0.05). Moreover, the serum level of P1NP from the YGYâ¯+â¯RLX group dramatically increased when compared with that from the YGY and RLX groups (YGY group: pâ¯<â¯0.05; RLX groups: pâ¯<â¯0.01). Notably, there was no significant difference between the YGY and YGYâ¯+â¯RLX groups. In addition, cell proliferation from the co-administration of YGY and RLX was clearly higher than a single use of YGY and RLX (pâ¯<â¯0.01, respectively). The ALP/BCA (alkaline phosphatase/bicinchoninic acid) in the YGYâ¯+â¯RLX group was higher than that in the RLX group (pâ¯<â¯0.01). CONCLUSION: Overall, co-administered YGY and RLX could partially attenuate bone loss and were more effective than individually using either one; this outcome might be associated with the proliferation and osteogenic differentiation of BMSCs.