Elahmer Nyruz Ramadan, Wong Sok Kuan, Mohamed Norazlina, Alias Ekram, Chin Kok-Yong, Muhammad Norliza
Department of Pharmacology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur 56000, Malaysia.
Department of Pharmacology, Pharmacy Faculty, Elmergib University, Al Khums 40414, Libya.
Biomedicines. 2024 Jul 23;12(8):1635. doi: 10.3390/biomedicines12081635.
Osteoporosis, a metabolic bone disorder characterized by decreased bone mass per unit volume, poses a significant global health burden due to its association with heightened fracture risk and adverse impacts on patients' quality of life. This review synthesizes the current understanding of the pathophysiological mechanisms underlying osteoporosis, with a focus on key regulatory pathways governing osteoblast and osteoclast activities. These pathways include RANK/RANKL/OPG, Wingless-int (Wnt)/β-catenin, and Jagged1/Notch1 signaling, alongside the involvement of parathyroid hormone (PTH) signaling, cytokine networks, and kynurenine in bone remodeling. Pharmacotherapeutic interventions targeting these pathways play a pivotal role in osteoporosis management. Anti-resorptive agents, such as bisphosphonates, estrogen replacement therapy/hormone replacement therapy (ERT/HRT), selective estrogen receptor modulators (SERMs), calcitonin, anti-RANKL antibodies, and cathepsin K inhibitors, aim to mitigate bone resorption. Conversely, anabolic agents, including PTH and anti-sclerostin drugs, stimulate bone formation. In addition to pharmacotherapy, nutritional supplementation with calcium, vitamin D, and vitamin K2 holds promise for osteoporosis prevention. However, despite the availability of therapeutic options, a substantial proportion of osteoporotic patients remain untreated, highlighting the need for improved clinical management strategies. This comprehensive review aims to provide clinicians and researchers with a mechanistic understanding of osteoporosis pathogenesis and the therapeutic mechanisms of existing medications. By elucidating these insights, this review seeks to inform evidence-based decision-making and optimize therapeutic outcomes for patients with osteoporosis.
骨质疏松症是一种代谢性骨病，其特征是单位体积骨量减少，由于其与骨折风险增加以及对患者生活质量的不利影响相关，因此在全球范围内构成了重大的健康负担。本综述综合了目前对骨质疏松症潜在病理生理机制的理解，重点关注调控成骨细胞和破骨细胞活性的关键信号通路。这些通路包括核因子κB受体活化因子（RANK）/核因子κB受体活化因子配体（RANKL）/骨保护素（OPG）、无翅型MMTV整合位点家族成员（Wnt）/β-连环蛋白、锯齿状蛋白1（Jagged1）/Notch1信号通路，以及甲状旁腺激素（PTH）信号通路、细胞因子网络和犬尿氨酸在骨重塑中的作用。针对这些通路的药物治疗干预在骨质疏松症管理中起着关键作用。抗骨吸收药物，如双膦酸盐、雌激素替代疗法/激素替代疗法（ERT/HRT）、选择性雌激素受体调节剂（SERM）、降钙素、抗RANKL抗体和组织蛋白酶K抑制剂，旨在减轻骨吸收。相反，促合成代谢药物，包括PTH和抗硬化蛋白药物，刺激骨形成。除药物治疗外，补充钙、维生素D和维生素K2对预防骨质疏松症也有前景。然而，尽管有多种治疗选择，但仍有相当一部分骨质疏松症患者未得到治疗，这凸显了改善临床管理策略的必要性。本综述旨在为临床医生和研究人员提供对骨质疏松症发病机制和现有药物治疗机制的深入理解。通过阐明这些见解，本综述旨在为基于证据的决策提供信息，并优化骨质疏松症患者的治疗效果。
