Wang Rui-Ang, Xu Chen-Xi
School of Medicine, Yangzhou University, Yangzhou, Jiangsu Province, 225001, People's Republic of China.
J Multidiscip Healthc. 2025 Jul 19;18:4121-4131. doi: 10.2147/JMDH.S526091. eCollection 2025.
Stable angina pectoris (SAP) and osteoporosis (OP) are both prevalent conditions among the elderly population. Compared to SAP, the prevention and management of OP are often neglected. Furthermore, certain medications used long-term for SAP may exert significant effects on bone metabolism. This review summarizes the impact of commonly prescribed SAP medications on OP. Extensive research indicates that nitrates not only promote vascular and osteogenic coupling via the nitric oxide (NO)-cyclic guanosine monophosphate (cGMP)-protein kinase G (PKG) pathway, enhancing the osteogenic effects of estrogen and mechanical stimulation, but also regulate bone immunity through receptor-interacting protein kinase 3 (RIPK3), promoting bone remodeling. β-Blockers promote osteoblast proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) via the cAMP/PKA signaling pathway, stimulating bone formation, while concurrently inhibiting osteoclasts and reducing bone resorption. Statins, which inhibit 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase to regulate lipid metabolism, also upregulate bone morphogenetic protein 2 (BMP-2) expression, inducing osteogenic differentiation of BMSCs, and inhibit osteoclast differentiation and activity, thereby promoting bone formation and suppressing bone resorption. Aspirin (AS) activates osteoblasts and their precursor cells, stimulates angiogenesis, mitigates inflammatory responses, promotes bone regeneration, and accelerates bone repair. However, clopidogrel reduces osteoblast numbers via P2 receptor-mediated extracellular nucleotide signaling and promotes adipogenic differentiation of BMSCs; furthermore, its metabolism can decrease serum 25-hydroxyvitamin D levels, adversely affecting skeletal health. Calcium channel blockers (CCBs) exhibit a largely neutral effect on bone health in clinical evidence, although basic research suggests potential benefits. The heterogeneity in research findings profoundly reflects the complexity of bone metabolism and the limitations of current studies. Synthesizing the evidence, preferential consideration may be given to nitrates, β-blockers, statins, and aspirin for SAP patients with coexisting OP or at significant risk; when clopidogrel is used, enhanced monitoring of bone parameters and intensified prevention and treatment of OP are recommended.
稳定型心绞痛(SAP)和骨质疏松症(OP)在老年人群中都很常见。与SAP相比,OP的预防和管理常常被忽视。此外,长期用于治疗SAP的某些药物可能会对骨代谢产生显著影响。本综述总结了常用的SAP药物对OP的影响。广泛的研究表明,硝酸盐不仅通过一氧化氮(NO)-环磷酸鸟苷(cGMP)-蛋白激酶G(PKG)途径促进血管与成骨耦合,增强雌激素和成骨刺激的成骨作用,还通过受体相互作用蛋白激酶3(RIPK3)调节骨免疫,促进骨重塑。β受体阻滞剂通过cAMP/PKA信号通路促进成骨细胞增殖和骨髓间充质干细胞(BMSC)的成骨分化,刺激骨形成,同时抑制破骨细胞并减少骨吸收。他汀类药物通过抑制3-羟基-3-甲基戊二酰辅酶A(HMG-CoA)还原酶来调节脂质代谢,还上调骨形态发生蛋白2(BMP-2)的表达,诱导BMSC的成骨分化,并抑制破骨细胞分化和活性,从而促进骨形成并抑制骨吸收。阿司匹林(AS)激活成骨细胞及其前体细胞,刺激血管生成,减轻炎症反应,促进骨再生,并加速骨修复。然而,氯吡格雷通过P2受体介导的细胞外核苷酸信号传导减少成骨细胞数量,并促进BMSC的脂肪生成分化;此外,其代谢可降低血清25-羟基维生素D水平,对骨骼健康产生不利影响。钙通道阻滞剂(CCB)在临床证据中对骨骼健康的影响大多呈中性,尽管基础研究表明可能有益。研究结果的异质性深刻反映了骨代谢的复杂性和当前研究的局限性。综合证据,对于合并OP或有高风险的SAP患者,可优先考虑使用硝酸盐、β受体阻滞剂、他汀类药物和阿司匹林;使用氯吡格雷时,建议加强对骨参数的监测,并强化OP的预防和治疗。