绝经后和药物治疗后的骨质疏松症：骨丢失的分子机制及其治疗
Osteoporosis After Menopause and After Drug Therapy: The Molecular Mechanism of Bone Loss and Its Treatment.
摘要(中文译文)
骨质疏松症是一种普遍的骨骼疾病，其特征是骨量减少和微结构恶化，导致骨折风险增加，特别是在老年人群中。绝经后骨质疏松症（PMOP）仍然是最常见的原发性形式，是由绝经后突然的雌激素缺乏引起的，雌激素缺乏通过加速核因子κB配体（RANKL）介导的破骨细胞生成的受体激活剂、抑制Wnt/β-catenin信号传导和促进炎性细胞因子的产生来破坏骨重塑。相比之下，药物性骨质疏松症（DIOP）包括一组由药物暴露引起的异质性继发性骨疾病。糖皮质激素抑制成骨细胞生成，增强破骨细胞活性，增加活性氧；长期双膦酸盐治疗可能会过度抑制骨转换，导致微损伤积聚；denosumab撤药会引发RANKL活性的独特反弹激增，通常会导致快速骨丢失和多发性椎体骨折。芳香化酶抑制剂、选择性血清素再摄取抑制剂、质子泵抑制剂、肝素和抗癫痫药物等药物通过多种机制损害骨质量。标准的抗骨吸收药物仍然是一线疗法，而特立帕肽、阿巴洛帕肽和romosozumab等合成代谢药物在高危或药物抑制的骨状态下提供了增强的益处。在停用denosumab时，过渡性双膦酸盐治疗至关重要，包括药物假期、生活方式干预和监测弱势患者在内的个性化治疗计划对于优化结果至关重要。新兴的方法，如基于小干扰RNA（siRNA）的疗法、抗硬骨素药物、数字监测技术和再生策略，为未来的精准医学管理带来了希望。了解骨质疏松症的不同和重叠的分子机制对于改善骨折预防和长期骨骼健康至关重要。
Abstract
Osteoporosis is a prevalent skeletal disorder characterized by reduced bone mass and microarchitectural deterioration, leading to increased fracture risk, particularly in aging populations. Postmenopausal osteoporosis (PMOP) remains the most common primary form and results from abrupt estrogen deficiency after menopause, which disrupts bone remodeling by accelerating the receptor activator of nuclear factor-κB ligand (RANKL)-mediated osteoclastogenesis, suppressing Wnt/β-catenin signaling, and promoting inflammatory cytokine production. In contrast, drug-induced osteoporosis (DIOP) encompasses a heterogeneous group of secondary bone disorders arising from pharmacologic exposures. Glucocorticoids suppress osteoblastogenesis, enhance osteoclast activity, and increase reactive oxygen species; long-term bisphosphonate therapy may oversuppress bone turnover, resulting in microdamage accumulation; denosumab withdrawal triggers a unique rebound surge in RANKL activity, often leading to rapid bone loss and multiple vertebral fractures. Medications including aromatase inhibitors, SSRIs, proton pump inhibitors, heparin, and antiepileptic drugs impair bone quality through diverse mechanisms. Standard antiresorptive agents remain first-line therapies, while anabolic agents such as teriparatide, abaloparatide, and romosozumab provide enhanced benefits in high-risk or drug-suppressed bone states. Transitional bisphosphonate therapy is essential when discontinuing denosumab, and individualized treatment plans-including drug holidays, lifestyle interventions, and monitoring vulnerable patients-are critical for optimizing outcomes. Emerging approaches such as small interfering RNA (siRNA)-based therapeutics, anti-sclerostin agents, digital monitoring technologies, and regenerative strategies show promise for future precision medicine management. Understanding the distinct and overlapping molecular mechanisms of osteoporosis is essential for improving fracture prevention and long-term skeletal health.
如何引用
AMA
Kelly I-Rong Lee, Jie-Hong Chen, Kuo-Hu Chen. Osteoporosis After Menopause and After Drug Therapy: The Molecular Mechanism of Bone Loss and Its Treatment.. International journal of molecular sciences. 2026; doi:10.3390/ijms27020641.
APA
Kelly I-Rong Lee, Jie-Hong Chen, Kuo-Hu Chen (2026). Osteoporosis After Menopause and After Drug Therapy: The Molecular Mechanism of Bone Loss and Its Treatment.. International journal of molecular sciences. https://doi.org/10.3390/ijms27020641
GB/T 7714
Kelly I-Rong Lee, Jie-Hong Chen, Kuo-Hu Chen. Osteoporosis After Menopause and After Drug Therapy: The Molecular Mechanism of Bone Loss and Its Treatment.[J]. International journal of molecular sciences, 2026 doi:10.3390/ijms27020641.
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