Year: 2025 | Month: May | Volume: 12 | Issue: 5 | Pages: 241-262
DOI: https://doi.org/10.52403/ijrr.20250528
Osteoporosis: A Comprehensive Review of Pathophysiological Mechanisms and Current Therapeutic Approaches
Santosh Nidagundi1, Nayeem A. Khatib2, Naveen R. Maledavar3, Kshitij A. Lele4
Department of Pharmacology and Toxicology;
KLE College of Pharmacy Belagavi, KLE Academy of Higher Education and Research, Belagavi, Karnataka, India.
Corresponding Author: Nayeem A. Khatib
ABSTRACT
Osteoporosis is a chronic skeletal disorder characterized by decreased bone mineral density and deterioration of bone microarchitecture, leading to increased fracture risk. This review outlines the multifactorial pathophysiology of osteoporosis, emphasizing the impact of estrogen deficiency, oxidative stress, pro- and anti-inflammatory cytokines, and disruption of key molecular pathways such as RANK/RANKL/OPG and Wnt/β-catenin. These factors collectively impair the balance between bone resorption and formation, with glucocorticoid use further exacerbating bone loss. Therapeutic strategies are broadly classified into antiresorptive agents—including bisphosphonates, SERMs, denosumab, calcitonin, and cathepsin K inhibitors—and anabolic agents such as teriparatide, abaloparatide, and statins. Dual-action therapies like romosozumab, along with combination and sequential regimens, offer potential for enhanced efficacy, particularly in high-risk individuals. Despite significant advances, treatment-related adverse effects and limitations persist. The review highlights the necessity for developing safer, more targeted interventions that can restore bone homeostasis with improved long-term outcomes. A mechanistic understanding of bone remodeling and personalized therapeutic strategies remain essential to effectively manage and prevent osteoporosis.
Keywords: Osteoporosis, Bone Remodeling, Estrogen Deficiency, RANK/RANKL/OPG Pathway, Wnt/β-Catenin Signaling, Oxidative Stress, Glucocorticoid-Induced Osteoporosis, Antiresorptive Agents, Anabolic Therapies, Dual and Sequential Treatment Strategies.
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