Anti-osteoporosis Effect of 5-Bromo-2-(4-chlorobenzoyl)-(Z)-3-(2-cyano-3-hydroxybut-2-enonyl)aminobenzo[b]furan: a Novel Selective Estrogen Receptor Modulator

Fukuyama, Ryo; Shimokawa, Akio; Kodama, Yasushi; Fujita, Mitsugu; Ohishi, Yoshitaka; Ando, Yuko; Koida, Masao; Nakamuta, Hiromichi

Abstract. The benzo[b]furan derivative MU314 inhibits in vitro bone resorption as potently as β-estradiol (E2). Here, we examined the point of action on the anti-osteoporotic effects of MU314. MU314 (10 nM) suppressed lacunae formation by osteoclastic cells and ICI-182,780, a pure E2 antagonist, inhibited this effect. Specifically, we ovariectomized (OVX) Wistar female rats and subcutaneously injected them with either MU314 (30 or 100 μg/kg) or E2 (100 μg/kg) over an 8-week period. Bone mineral content (BMC) in the proximal end of the tibia was significantly decreased (14%) in OVX rats, and MU314 (100 μg/kg) and E2 significantly suppressed the decline in BMC. OVX rats exhibited decreased cancellous bone in the proximal end of the tibia and induced destruction of its trabecular structure. MU314 suppressed these changes. OVX also reduced the mechanical strength of the femoral neck, which was also recovered by MU314 and E2. E2 completely protected against OVX-induced uterine atrophy, but MU314 had no effect. These results strongly indicate that MU314 acts as a selective estrogen receptor modulator.