To evaluate the inhibitory effects of prophylactic administration of α-zearalanol (α-ZAL) on bone microarchitecture and bone resorption activity in ovariectomized osteoporotic rats, and to investigate its regulatory effects on the osteogenic and adipogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). A total of 60 6-month-old unmated female Sprague-Dawley (SD) rats weighing (300 ± 20) g were randomly divided into the sham surgery group (Sham group), ovariectomy group (OVX group), solvent group (Oil group), estradiol benzoate treatment group (Post-E2 group), α-ZAL prevention group (Pre-ZAL group), and α-ZAL treatment group (Post-ZAL group), with 10 rats in each group. An osteoporosis rat model was established using the ovariectomy method. Rats in the Sham group underwent the same surgical procedures except for ovarian removal. Seventy-two hours after ovarian removal, the Oil group received intramuscular injections of 0.5 mL of oil solvent, and the Pre-ZAL group received intramuscular injections of α-ZAL (1.5 mg·kg－1), administered every 3 days for 120 consecutive days. The Post-E2 group and Post-ZAL group began intramuscular injections of estradiol benzoate (1.5 mg·kg－1) and α-ZAL (1.5 mg·kg－1), respectively, 90 days after ovariectomy, administered every 3 days for 120 consecutive days. After drug administration, bone density and bone tissue microstructure morphology were analyzed using a micro-CT small animal in vivo imaging system and staining methods. Osteoclasts were isolated and their activity was detected. Femoral BMSCs were obtained to assess their osteoblast and adipocyte differentiation capabilities, and uterine tissue morphological changes were observed via histological sections. Compared with the OVX group, BMD in the Sham group, Post-E2 group, Pre-ZAL group, and Post-ZAL group increased by 133.12%, 75.97%, 69.64%, and 24.69%, respectively (all P 0.05). Tb.N in the Sham group, Post-E2 group, Pre-ZAL group, and Post-ZAL group increased by 160.08%, 118.14%, 94.76%, and 46.76%, respectively, compared with the OVX group (all P 0.05). MMP-9, TRAP, and CK mRNA expression was significantly downregulated in both the Post-E2 group and the Pre-ZAL group (P 0.05). There was no significant increase in body weight in the Post-E2, Pre-ZAL, and Post-ZAL groups, but uterine weight significantly increased in the Post-E2 group (P 0.05), and no significant changes were observed in uterine epithelium. α-ZAL can effectively protect bone mass, improve bone microstructure, and reduce estrogen-related uterine adverse reactions by regulating the osteogenic/adipogenic differentiation balance of BMSCs, providing a potential new therapeutic strategy for the prevention and treatment of postmenopausal osteoporosis.
He et al. (2025) studied this question.