Effects of Cockle-Shell-Derived CaO-Based Formulation on Bone Loss and Selected Metabolic Outcomes in Ovariectomized Rats

Postmenopausal estrogen deficiency induces complex physiological alterations, notably osteoporosis and metabolic dysfunction. This study investigated the effect of High Active Calcium (HAC) using in vitro and ovariectomized (OVX) rat models. In vitro, HAC significantly inhibited RANKL-induced osteoclastogenesis in RAW264.7 cells. In vivo, HAC administration improved bone mineral density (BMD) and trabecular microarchitecture while normalizing serum calcium and reducing bone resorption markers. Qualitative H&E assessment showed differences in bone morphology among groups. HAC treatment attenuated the OVX-induced elevation in serum ALP activity and reduced the Glu-OC/Gla-OC ratio, indicating changes in bone turnover-related markers. HAC partially restored uterine estrogen receptor-alpha (ERα) expression and markedly downregulated hepatic inflammatory cytokines (TNF-α, IL-6, IL-1β). Overall, HAC treatment was associated with improvements in bone remodeling-related markers and reduced hepatic inflammatory cytokine expression in OVX rats. These findings support further preclinical evaluation of HAC as a calcium-based nutritional supplement for estrogen deficiency-associated bone loss.