CALCIUM HOMEOSTASIS, LIPID PROFILE AND OXIDATIVE STRESS IN OSTEOPOROSIS: MEDICAL-CHEMICAL MECHANISMS OF BONE REMODELING AND BONE-VASCULAR COMORBIDITY

Abstract

Introduction. Osteoporosis is a systemic metabolic skeletal disease in which decreased bone mineral density, impaired microarchitecture and in-creased fracture risk are associated not only with calcium and vitamin D deficiency, but also with dysregulation of calcium-phosphate metabolism, hormonal deficiency, lipid abnormalities, chronic inflammation, oxidative stress and impaired coupling between osteoclastic and osteoblastic phases of bone remodeling. From the perspective of medicinal chemistry, hydroxyapatite structure, calcium and phosphate metabolism, parathyroid hormone, vitamin D, FGF23, RANK/RANKL/OPG balance, Wnt/β-catenin signaling, PPARγ-dependent adipogenic differentiation of mesenchymal stromal cells, lipid peroxidation and antioxidant systems are of particular importance. Objective – to summarize current data on the relationship between calcium homeostasis, lipid profile, and oxidative stress in osteoporosis, with a focus on the medical-chemical mechanisms of bone remodeling, biological incorporation of calcium into the bone matrix, bone-vascular comorbidity, and potential laboratory targets for further research. Main points. Bone tissue is a dynamic mineralized system in which hydroxyapatite crystals interact with collagen matrix, osteoblasts, osteoclasts, osteocytes and the vascular microenvironment. Calcium homeostasis is regulated by vitamin D, parathyroid hormone, calcitonin, FGF23, renal han-dling, and intestinal absorption; it is essential to distinguish between calcium intake, calcium bioavailability, and its incorporation into the mineralized matrix. Lipid profile affects osteogenesis via PPARγ, Wnt/β-catenin, cytokines and oxidized lipoproteins. Oxidative stress disrupts remodeling through osteoblast damage, RANKL/OPG imbalance, RUNX2 suppression and lipid peroxidation. Conclusion. Osteoporosis should be considered as a systemic disorder of mineral, lipid, hormonal and redox metabolism. A comprehensive laborato-ry panel including calcium, phosphate, 25(OH)D, parathyroid hormone, FGF23, alkaline phosphatase, P1NP, β-CTX, lipid profile, oxidized lipoproteins, malondialdehyde, 4-hydroxynonenal, GSH/GSSG, superoxide dismutase, catalase, glutathione peroxidase, hsCRP, IL-6, TNF-α, osteocalcin, osteoprotegerin, RANKL, and sclerostin may be promising for a personalized approach to patient assess-ment and further research.