Romosozumab 可挽救糖尿病肾病小鼠模型中受损的骨量和骨强度

IF 2.1 Q3 ENDOCRINOLOGY & METABOLISM
Rachel Kohler , Dyann M. Segvich , Olivia Reul , Corinne E. Metzger , Matthew R. Allen , Joseph M. Wallace
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引用次数: 0

摘要

随着国际糖尿病发病率和慢性肾脏病(CKD)等糖尿病并发症发病率的不断攀升,需要采取干预措施来解决这种复杂疾病的高风险骨骼脆弱性问题。罗莫单抗(Romosozumab,Romo)是美国食品及药物管理局批准的一种硬骨素抑制剂,已被证明可增加轻度至重度慢性肾脏病骨质疏松患者的骨矿物质密度并降低骨折率,但其对糖尿病骨质疏松的影响尚不清楚。我们的目的是在糖尿病和慢性肾脏病联合模型中测试 Romo 的性能。利用之前建立的链脲佐菌素和腺嘌呤饮食诱导模型,将 6 周大的雄性 C57BL/6 小鼠随机分为对照组(CON)和疾病模型组(STZ-Ad)。疾病诱导 16 周后,CON 组和 STZ-Ad 组再分为两个治疗组,每周皮下注射 100 μL 的载体(磷缓冲盐水,PBS)或 10 mg/kg Romo。治疗 4 周后,小鼠经心脏放血和颈椎脱位安乐死。清除后肢骨骼和 L4 椎体上的软组织,用浸透 PBS 的纱布包裹并保存在 20C 温度下。通过微计算机断层扫描对右胫骨、股骨和 L4 椎骨进行扫描;然后对胫骨进行 4pt 弯曲测试,对 L4 椎骨进行压缩测试。在 STZ-Ad 和 CON 动物中,Romo 治疗明显增加了皮质和骨小梁的骨量。这些形态上的改善使皮质抗弯强度和骨小梁抗压强度相应增加,STZ-Ad 治疗小鼠在所有骨小梁力学指标上都超过了对照组小鼠。这些结果表明,Romo 在增加糖尿病肾病患者的骨量和骨强度方面仍然有效。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Romosozumab rescues impaired bone mass and strength in a murine model of diabetic kidney disease

As international incidence of diabetes and diabetes-driven comorbidities such as chronic kidney disease (CKD) continue to climb, interventions are needed that address the high-risk skeletal fragility of what is a complex disease state. Romosozumab (Romo) is an FDA-approved sclerostin inhibitor that has been shown to increase bone mineral density and decrease fracture rates in osteoporotic patients with mild to severe CKD, but its effect on diabetes-weakened bone is unknown. We aimed to test Romo's performance in a model of combined diabetes and CKD. 6-week old male C57BL/6 mice were randomly divided into control (CON) and disease model (STZ-Ad) groups, using a previously established streptozotocin- and adenine-diet-induced model. After 16 weeks of disease induction, both CON and STZ-Ad groups were subdivided into two treatment groups and given weekly subcutaneous injections of 100 μL vehicle (phosphorus buffered saline, PBS) or 10 mg/kg Romo. Mice were euthanized after 4 weeks of treatment via cardiac exsanguination and cervical dislocation. Hindlimb bones and L4 vertebrae were cleaned of soft tissue, wrapped in PBS-soaked gauze and stored at 20C. Right tibiae, femora, and L4s were scanned via microcomputed tomography; tibiae were then tested to failure in 4-pt bending while L4s were compression tested. Romo treatment significantly increased cortical and trabecular bone mass in both STZ-Ad and CON animals. These morphological improvements created corresponding increases in cortical bending strength and trabecular compression strength, with STZ-Ad treated mice surpassing vehicle CON mice in all trabecular mechanics measures. These results suggest that Romo retains its efficacy at increasing bone mass and strength in diabetic kidney disease.

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来源期刊
Bone Reports
Bone Reports Medicine-Orthopedics and Sports Medicine
CiteScore
4.30
自引率
4.00%
发文量
444
审稿时长
57 days
期刊介绍: Bone Reports is an interdisciplinary forum for the rapid publication of Original Research Articles and Case Reports across basic, translational and clinical aspects of bone and mineral metabolism. The journal publishes papers that are scientifically sound, with the peer review process focused principally on verifying sound methodologies, and correct data analysis and interpretation. We welcome studies either replicating or failing to replicate a previous study, and null findings. We fulfil a critical and current need to enhance research by publishing reproducibility studies and null findings.
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