Human Physiology, Health Science, Westville Campus, University of KwaZulu-Natal, Westville 4041, South Africa.
Pharmacology Division, University of Rhodes, Grahamstown 6139, South Africa.
Int J Mol Sci. 2023 Jul 26;24(15):11963. doi: 10.3390/ijms241511963.
Type 2 diabetes (T2D) is associated with a plethora of comorbidities, including osteoporosis, which occurs due to an imbalance between bone resorption and formation. Numerous mechanisms have been explored to understand this association, including the renin-angiotensin-aldosterone system (RAAS). An upregulated RAAS has been positively correlated with T2D and estrogen deficiency in comorbidities such as osteoporosis in humans and experimental studies. Therefore, research has focused on these associations in order to find ways to improve glucose handling, osteoporosis and the downstream effects of estrogen deficiency. Upregulation of RAAS may alter the bone microenvironment by altering the bone marrow inflammatory status by shifting the osteoprotegerin (OPG)/nuclear factor kappa-Β ligand (RANKL) ratio. The angiotensin-converting-enzyme/angiotensin II/Angiotensin II type 1 receptor (ACE/Ang II/AT1R) has been evidenced to promote osteoclastogenesis and decrease osteoblast formation and differentiation. ACE/Ang II/AT1R inhibits the wingless-related integration site (Wnt)/β-catenin pathway, which is integral in bone formation. While a lot of literature exists on the effects of RAAS and osteoporosis on T2D, the work is yet to be consolidated. Therefore, this review looks at RAAS activity in relation to osteoporosis and T2D. This review also highlights the relationship between RAAS activity, osteoporosis and estrogen deficiency in T2D.
2 型糖尿病（T2D）与许多合并症相关，包括骨质疏松症，这是由于骨吸收和形成之间的失衡引起的。已经探索了许多机制来理解这种关联，包括肾素-血管紧张素-醛固酮系统（RAAS）。在骨质疏松等合并症中，RAAS 的上调与 T2D 和雌激素缺乏呈正相关，在人类和实验研究中均如此。因此，研究集中在这些关联上，以寻找改善葡萄糖处理、骨质疏松症和雌激素缺乏下游影响的方法。RAAS 的上调可能通过改变骨髓炎症状态来改变骨微环境，从而改变护骨素（OPG）/核因子 kappa-B 配体（RANKL）的比值。已经有证据表明，血管紧张素转换酶/血管紧张素 II/血管紧张素 II 型 1 受体（ACE/Ang II/AT1R）促进破骨细胞形成，并减少成骨细胞的形成和分化。ACE/Ang II/AT1R 抑制 Wnt/β-连环蛋白通路，该通路是骨形成的重要组成部分。虽然有大量关于 RAAS 和骨质疏松症对 T2D 的影响的文献，但这些工作尚未得到整合。因此，本综述着眼于 RAAS 活性与骨质疏松症和 T2D 的关系。本综述还强调了 RAAS 活性、骨质疏松症和 T2D 中雌激素缺乏之间的关系。
