2-Fluoro-17β-estradiol attenuates ovariectomy-induced bone loss with minimal uterotrophic activity

Abstract

After menopause, estrogen deficiency accelerates bone loss. Hormone replacement therapy (HRT) improves this condition, but, increases the risk of estrogen-dependent malignancies. Unlike 17β-estradiol (E₂), 2-fluoro-17β-estradiol (2-FE₂) has been found not to induce mammary tumors in ACI rats. We evaluated the bone-protective effects of 2-FE₂ in ovariectomized (OVX) mice. Microcomputed tomography revealed significant trabecular bone loss in the OVX mice, which was substantially reduced by 2-FE2 treatment. Cancellous bone mineral density (BMD) was significantly restored by 2-FE₂ treatment, reaching levels comparable to those in E₂-treated mice, whereas cortical BMD did not change significantly. Importantly, unlike E₂, 2-FE₂ did not significantly increase the uterine weight. These findings demonstrate that 2-FE₂ effectively suppresses estrogen deficiency-induced bone loss with minimal uterotrophic activity. Thus, 2-FE₂ may represent a promising candidate for safer estrogen replacement therapy for postmenopausal osteoporosis.