Comparable Protective Effects of Low- and High-Dose MK-7 on Bone Structure and Remodeling in a Rat Model of Osteoporosis Induced by Estrogen Deficiency and Glucocorticoid Exposure

Background: Estrogen deficiency and glucocorticoid exposure are major contributors to osteoporosis. Although menaquinone-7 (MK-7) exhibits osteoprotective effects, whether low-dose supplementation is comparable to high-dose treatment remains unclear. Methods: Female Sprague–Dawley rats were assigned to sham control (SC), ovariectomy plus dexamethasone (OVX+Dex), and OVX+Dex treated with low-dose MK-7 (100 μg/kg) or high-dose MK-7 (20 mg/kg). Bone microarchitecture, histopathology, and serum bone turnover markers were evaluated. Results: OVX+Dex induced marked deterioration of trabecular bone microarchitecture, characterized by reduced bone volume and structural disruption. These changes were accompanied by increased osteoclast activity (cathepsin K), decreased osteogenic and extracellular matrix–related markers (cbfa-1, osteonectin, and biglycan), and downregulation of osteoprotegerin, indicating a pronounced imbalance in bone remodeling. Serum analysis further revealed reduced estradiol levels and alterations in circulating bone turnover markers, consistent with a dysregulated high-turnover state. Both low- and high-dose MK-7 significantly improved bone microarchitecture, restored remodeling-related protein expression, and partially normalized serum calcium-regulating hormones and bone turnover markers (all p < 0.05), with no significant differences observed between doses. Conclusions: MK-7 attenuates osteoporosis by restoring the balance between bone resorption and formation. Notably, low-dose MK-7 provides protective effects comparable to high-dose treatment, supporting its potential clinical utility.