Molecular Regulation of Bone Remodeling in Osteoporosis and Current Therapeutic Approaches

Osteoporosis arises from an imbalance in bone remodeling in which osteoclast resorption surpasses osteoblast activity. This process is regulated by the receptor activator of NF-κB ligand/receptor activator of NF-κB/osteoprotegerin system and Wnt/β-catenin signaling pathway, which are influenced by hormones, cytokines, and lifestyle factors. This condition adversely affects the quality of life by causing pain, restricted mobility, and increased mortality. Bone mineral density testing, including a fracture risk assessment tool, is part of the diagnostic process, along with laboratory tests to exclude secondary causes. Management strategies include lifestyle modifications, calcium and vitamin D supplementation, and pharmacological interventions, such as bisphosphonates, denosumab, and parathyroid hormone analogs. Moreover, nanoengineered biomaterials and scaffolds have emerged as promising approaches for hastening bone regeneration, specifically in osteoporotic fractures, by enhancing osteointegration, angiogenesis, and the meticulous release of osteoinductive chemicals. Promising treatments, such as sclerostin inhibitors, nanocarrier-based drug delivery systems, and natural antioxidants, control bone metabolism by attenuating oxidative stress and inflammation, thereby providing novel opportunities for disease management. This review provides a comprehensive and integrated perspective on the molecular regulation of bone remodeling by linking the RANK/RANKL/OPG axis, Wnt/β-catenin signaling, hormonal regulation, oxidative stress, and osteoimmune interactions with both established and emerging therapeutic strategies. Unlike previous reviews that primarily focus on individual mechanisms or treatments, it highlights recent advances in targeted molecular therapies, nanotechnology-based drug delivery, artificial intelligence-assisted fracture prediction, and regenerative approaches, offering a translational framework to support precision medicine and future clinical management of osteoporosis.