Division of Endocrinology and Centre for Research in ASTHI, CSIR-Central Drug Research Institute, Council of Scientific and Industrial Research, Lucknow, 226031, India.
Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201002, India.
Food Funct. 2022 Feb 21;13(4):2184-2199. doi: 10.1039/d1fo03867b.
Kidney Disease Improving Global Outcomes (KDIGO) 2017 Clinical Practice Guideline has recommended treatment decisions for patients with chronic kidney disease (CKD) with osteoporosis and/or high risk of fracture. Bisphosphonates, the first-line anti-osteoporosis drugs have the concern of worsening kidney functions. Moreover, despite impaired bone formation in CKD patients, teriparatide, the formation-stimulating drug is not recommended. Thus, there is an urgent need for safe and effective treatment of osteoporosis in CKD patients. Here, in CKD rats, we tested the osteoprotective effect of diosmin, a citrus-derived bioflavonoid used as a phlebotonic in chronic venous insufficiency and has a renoprotective effect. CKD was developed by 5/6 nephrectomy and diosmin at the human equivalent dose (100 mg kg) did not advance renal failure but reduced blood pressure to the level of sham control. Fibroblast growth factor-23 and parathyroid hormone were increased in CKD and diosmin suppressed both. CKD reduced bone mass and deteriorated the microarchitecture of trabecular bones, and diosmin maintained both to control levels. Bone formation and strength were impaired in the CKD and diosmin maintained these levels to control levels. Nanoindentation of bone showed that diosmin significantly increased tissue hardness over the control. Diosmetin, the metabolic surrogate of diosmin had comparable pharmacokinetic profiles between the control and CKD groups. Furthermore, diosmetin (50 mg kg) protected against CKD-induced bone loss. These data suggest that diosmin and its metabolic surrogate, diosmetin protect against CKD-induced osteopenia. Since diosmin has no renal adverse effect and protected bone mass and strength in CKD rats, we propose assessing its anti-osteoporosis effect in CKD patients.
肾脏疾病改善全球结果组织(KDIGO)2017 年临床实践指南推荐了骨质疏松症和/或骨折高风险的慢性肾脏病(CKD)患者的治疗决策。双膦酸盐是一线抗骨质疏松药物,但其会导致肾功能恶化。此外,尽管 CKD 患者的骨形成受损,但不推荐使用甲状旁腺素形成刺激药物特立帕肽。因此,迫切需要为 CKD 患者提供安全有效的骨质疏松症治疗方法。在这里,我们在 CKD 大鼠中测试了橙皮苷的骨保护作用,橙皮苷是一种来源于柑橘的生物类黄酮,用于治疗慢性静脉功能不全,具有肾脏保护作用。CKD 通过 5/6 肾切除术发展而来,人类等效剂量(100mg/kg)的橙皮苷不会导致肾功能衰竭,但可降低血压至假手术对照组的水平。成纤维细胞生长因子-23 和甲状旁腺激素在 CKD 中增加,而橙皮苷抑制了这两种激素。CKD 降低了骨量并恶化了小梁骨的微观结构,而橙皮苷则将其维持在对照水平。CKD 降低了骨形成和骨强度,而橙皮苷则将其维持在对照水平。骨的纳米压痕表明,橙皮苷显著增加了组织硬度,超过了对照组。橙皮苷的代谢物橙皮苷在对照组和 CKD 组之间具有相似的药代动力学特征。此外,橙皮苷(50mg/kg)可预防 CKD 引起的骨丢失。这些数据表明,橙皮苷及其代谢物橙皮苷可预防 CKD 引起的骨质疏松症。由于橙皮苷对肾脏没有不良影响,并保护 CKD 大鼠的骨量和强度,因此我们建议在 CKD 患者中评估其抗骨质疏松作用。