Sigma Anti-bonding Calcium Attenuates Ovariectomy-Induced Bone Loss by Preserving Trabecular Microarchitecture and Suppressing Osteoclastogenesis.

Estrogen deficiency-induced osteoporosis is characterized by increased bone resorption and progressive deterioration of trabecular microarchitecture, leading to skeletal fragility. This study investigated the effects of sigma anti-bonding calcium (SAC), a formulation designed to enhance ion release, in an ovariectomized (OVX) mouse model and in RANKL-induced osteoclastogenesis in vitro. Female mice underwent OVX and received oral SAC (100 or 200 mg/kg/day) for 13 weeks following surgery. Body and major organ weights were monitored during the experimental period. SAC administration did not significantly affect body or major organ weights under the conditions examined. Micro-computed tomography demonstrated that SAC attenuated OVX-induced trabecular deterioration, as evidenced by preservation of bone mineral density (BMD), partial restoration of trabecular number, and reduction of structural model index, whereas trabecular thickness and separation were minimally affected. Histological analysis further confirmed preservation of trabecular bone area in SAC-treated mice, whereas marrow adiposity assessed by Oil Red O staining was not markedly altered. Serum analysis revealed that SAC significantly reduced OVX-induced elevation of C-terminal telopeptide of type I collagen (CTX), while formation-associated markers did not show consistent recovery. In vitro, SAC suppressed RANKL-induced osteoclast differentiation in RAW264.7 cells without significantly affecting cell viability at the concentrations examined. SAC dose-dependently reduced the mRNA expression of osteoclast-related genes, including TRAP, NFATc1, Ctsk, and Atp6v0d2, and attenuated NFATc1 protein induction. SAC treatment was associated with reduced RANKL-stimulated p38 phosphorylation without changes in total p38 expression and with decreased MITF protein expression. Collectively, these findings indicate that SAC attenuates estrogen deficiency-associated trabecular bone deterioration and suppresses osteoclast differentiation, accompanied by changes in p38 phosphorylation and NFATc1 and MITF expression. These findings support further investigation of SAC as a potential adjunctive approach for attenuating estrogen deficiency-associated bone loss; however, comparative studies with conventional calcium formulations are required to determine whether the observed effects are specific to SAC.