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Are Bisphosphonates Associated with Adverse Metabolic and Cognitive Effects? A Study in Intact Rats and Rats Fed High-Fat High-Fructose Diet.
Calcified Tissue International ( IF 3.3 ) Pub Date : 2020-03-24 , DOI: 10.1007/s00223-020-00684-5
Silvia Gancheva 1 , Maria Zhelyazkova-Savova 1
Affiliation  

Osteocalcin, known as a bone gla protein, is considered a regulator of energy metabolism and behavior in its undercarboxylated form (ucOC). Antiresorptive drugs, such as alendronate, reduce serum level of ucOC. The purpose of the current study was to verify if alendronate might impact on energy metabolism and animal behavior by reducing ucOC level and to find out if the presence of metabolic alterations would further worsen these potential adverse effects. Four groups of male Wistar rats (12 per group) were used: a control group, a group receiving high-fat high-fructose diet (HFHF), a group treated with alendronate, and a group receiving alendronate and HFHF. Alendronate was administered subcutaneously in a dose of 50 mcg/kg thrice weekly. Study duration was 15 weeks. Animals were tested for locomotion, anxiety and spatial memory. Glucose and insulin tolerance tests evaluated the glucose metabolism. Visceral obesity was assessed by the weight of right retroperitoneal fat pads. Concentration of ucOC was measured in the serum. Alendronate reduced serum ucOC concentration, increased fasting blood glucose level, and worsened insulin sensitivity. It did not increase visceral adiposity. Fat index was negatively correlated with ucOC in all animals and in the alendronate-treated rats. Alendronate worsened spatial memory of the animals and ucOC levels correlated positively with their cognitive performance.



中文翻译:

双膦酸盐是否与不良的代谢和认知作用有关?完整大鼠和高脂高果糖饮食大鼠的研究。

骨钙素被称为骨gla蛋白,被认为是能量代谢和行为的调节剂,其羧化程度不足(ucOC)。抗吸收药,例如阿仑膦酸钠,可降低ucOC的血清水平。本研究的目的是通过降低ucOC水平来验证阿仑膦酸盐是否可能对能量代谢和动物行为产生影响,并确定是否存在代谢改变会进一步加剧这些潜在的不良反应。使用四组雄性Wistar大鼠(每组12只):对照组,接受高脂高果糖饮食(HFHF)的组,接受阿仑膦酸盐治疗的组和接受阿仑膦酸盐和HFHF的组。皮下注射阿仑膦酸酯,每周三次,剂量为50 mcg / kg。研究持续时间为15周。测试动物的运动,焦虑和空间记忆。葡萄糖和胰岛素耐受性测试评估了葡萄糖的代谢。通过右腹膜后脂肪垫的重量评估内脏肥胖。测量血清中ucOC的浓度。阿仑膦酸盐降低血清ucOC浓度,增加空腹血糖水平,并恶化胰岛素敏感性。它没有增加内脏脂肪。在所有动物和阿仑膦酸盐治疗的大鼠中,脂肪指数与ucOC呈负相关。阿仑膦酸盐使动物的空间记忆恶化,并且ucOC水平与其认知能力呈正相关。并加剧胰岛素敏感性。它没有增加内脏脂肪。在所有动物和阿仑膦酸盐治疗的大鼠中,脂肪指数与ucOC呈负相关。阿仑膦酸盐使动物的空间记忆恶化,并且ucOC水平与其认知能力呈正相关。并加剧胰岛素敏感性。它没有增加内脏脂肪。在所有动物和阿仑膦酸盐治疗的大鼠中,脂肪指数与ucOC呈负相关。阿仑膦酸盐使动物的空间记忆恶化,并且ucOC水平与其认知能力呈正相关。

更新日期:2020-03-24
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