Raloxifene prevents skeletal fragility in adult female Zucker Diabetic Sprague-Dawley rats.
Raloxifene prevents skeletal fragility in adult female Zucker Diabetic Sprague-Dawley rats.
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DOI：
10.1371/journal.pone.0108262
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Burr DB
中科院分区：
文献类型：
--
作者：
Hill Gallant KM;Gallant MA;Brown DM;Sato AY;Williams JN;Burr DB
尽管骨矿物质密度正常或较高，2 型糖尿病患者的骨折风险仍会增加，这表明骨质量差是一个危险因素。雷洛昔芬改善骨材料和机械性能，与骨矿物质密度无关。本研究旨在确定雷洛昔芬是否可以预防糖尿病对易患糖尿病的大鼠骨骼脆弱性的负面影响。成年 Zucker 糖尿病 Sprague-Dawley (ZDSD) 雌性大鼠（20 周龄，n = 24）被喂食致糖尿病的高脂肪饮食，并随机接受每日皮下注射雷洛昔芬或载体，持续 12 周。每周测量血糖，并在基线和第 12 周测量糖化血红蛋白。处死时，采集股骨和腰椎用于成像和机械测试。与媒介物治疗的大鼠相比，雷洛昔芬治疗的大鼠 2 型糖尿病的发病率较低。此外，雷洛昔芬治疗的大鼠的血糖水平显着低于糖尿病载体治疗的大鼠以及未患糖尿病的载体治疗的大鼠。与糖尿病和非糖尿病媒介物治疗的 ZDSD 大鼠相比，雷洛昔芬治疗的大鼠的股骨韧性更大，因为应力应变曲线的屈服后区域的能量吸收更大。在失效能量、屈服后失效能量和屈服后位移的结构（外在）机械性能方面，观察到了组间的类似差异。这些结果表明，雷洛昔芬有益于预防糖尿病的发生并改善易患糖尿病的 ZDSD 大鼠的骨材料特性。如果这些结果能够得到未来的实验和临床研究的支持，这表明雷洛昔芬在保持糖尿病骨质量以及预防糖尿病方面具有独特的治疗潜力。
Fracture risk in type 2 diabetes is increased despite normal or high bone mineral density, implicating poor bone quality as a risk factor. Raloxifene improves bone material and mechanical properties independent of bone mineral density. This study aimed to determine if raloxifene prevents the negative effects of diabetes on skeletal fragility in diabetes-prone rats. Adult Zucker Diabetic Sprague-Dawley (ZDSD) female rats (20-week-old, n = 24) were fed a diabetogenic high-fat diet and were randomized to receive daily subcutaneous injections of raloxifene or vehicle for 12 weeks. Blood glucose was measured weekly and glycated hemoglobin was measured at baseline and 12 weeks. At sacrifice, femora and lumbar vertebrae were harvested for imaging and mechanical testing. Raloxifene-treated rats had a lower incidence of type 2 diabetes compared with vehicle-treated rats. In addition, raloxifene-treated rats had blood glucose levels significantly lower than both diabetic vehicle-treated rats as well as vehicle-treated rats that did not become diabetic. Femoral toughness was greater in raloxifene-treated rats compared with both diabetic and non-diabetic vehicle-treated ZDSD rats, due to greater energy absorption in the post-yield region of the stress-strain curve. Similar differences between groups were observed for the structural (extrinsic) mechanical properties of energy-to-failure, post-yield energy-to-failure, and post-yield displacement. These results show that raloxifene is beneficial in preventing the onset of diabetes and improving bone material properties in the diabetes-prone ZDSD rat. This presents unique therapeutic potential for raloxifene in preserving bone quality in diabetes as well as in diabetes prevention, if these results can be supported by future experimental and clinical studies.
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影响因子：
4.1
作者：
Gallant, Maxime A.;Brown, Drew M.;Hammond, Max;Wallace, Joseph M.;Du, Jiang;Deymier-Black, Alix C.;Almer, Jonathan D.;Stock, Stuart R.;Allen, Matthew R.;Burr, David B.
通讯作者：
Burr, David B.
影响因子：
120.7
作者：
Narayan, KMV;Boyle, JP;Williamson, DF
通讯作者：
Williamson, DF
影响因子：
11.1
作者：
Sambrook, PN;Geusens, P;Melton, ME
通讯作者：
Melton, ME
DOI：
10.1152/ajpendo.90937.2008
发表时间：
2009-04-01
影响因子：
5.1
作者：
Reinwald, Susan;Peterson, Richard G.;Burr, David B.
通讯作者：
Burr, David B.
影响因子：
15.9
作者：
Tiano, Joseph P.;Delghingaro-Augusto, Viviane;Mauvais-Jarvis, Franck
通讯作者：
Mauvais-Jarvis, Franck