Fronczek-Sokół Justyna, Pytlik Maria
Department of Pharmacology, Medical University of Silesia, Sosnowiec, Poland.
Pharmacol Rep. 2014 Jun;66(3):412-7. doi: 10.1016/j.pharep.2013.12.013. Epub 2014 Apr 13.
Diabetes mellitus type 2 and osteoporosis are major health problem, especially in postmenopausal women. Glimepiride is a third-generation sulfonylurea derivative and is used as a first-line drug in the treatment of type 2 diabetes mellitus. The effect of this drug on bone tissue is unknown. The aim of the present study was to investigate the influence of glimepiride on the skeletal system in ovariectomized and non-ovariectomized rats.
The experiment was conducted on 3-month-old female Wistar rats, divided into 4 groups (n=10 per group): I (NOVX)-non-ovariectomized control rats, II (NOVX+G)-non-ovariectomized rats receiving glimepiride (0.8 mg/kg po), III (OVX)-ovariectomized control rats, IV (OVX+G)-ovariectomized rats receiving glimepiride (0.8 mg/kg po). Bilateral ovariectomy was performed 7 days before the start of the experiment, under ketamine-xylazine anesthesia. Glimepiride was administered once daily for 28 days. The effect of glimepiride on the skeletal system was assessed based on macrometric parameters, histomorphometric parameters and mechanical properties of the tibial metaphysis, femoral diaphysis and femoral neck. Bone mass, mineral mass, calcium and phosphorus content, as well as serum estrogen, osteocalcin and RatLaps levels were also studied.
Estrogen deficiency in ovariectomized rats caused increased bone remodeling, with an intensification of bone resorption and formation, and mineralization impairment. Glimepiride in ovariectomized rats inhibited the development of changes in the skeletal system caused by estrogen deficiency, intensifying bone formation. In the presence of estrogens (in non-ovariectomized rats), glimepiride also intensified bone formation, but to a lesser extent.
Glimepiride, in the therapy of type 2 diabetes mellitus in postmenopausal women, may have a beneficial effect on bone remodeling and may reduce the risk of development of osteoporosis.
2型糖尿病和骨质疏松症是主要的健康问题，在绝经后女性中尤为突出。格列美脲是第三代磺酰脲衍生物，用作治疗2型糖尿病的一线药物。该药物对骨组织的影响尚不清楚。本研究的目的是调查格列美脲对去卵巢和未去卵巢大鼠骨骼系统的影响。
实验选用3月龄雌性Wistar大鼠，分为4组（每组n = 10）：I组（NOVX）-未去卵巢对照大鼠，II组（NOVX + G）-接受格列美脲（0.8 mg/kg口服）的未去卵巢大鼠，III组（OVX）-去卵巢对照大鼠，IV组（OVX + G）-接受格列美脲（0.8 mg/kg口服）的去卵巢大鼠。在实验开始前7天，在氯胺酮-赛拉嗪麻醉下进行双侧卵巢切除术。格列美脲每天给药一次，持续28天。基于胫骨近端、股骨干和股骨颈的宏观参数、组织形态计量学参数和力学性能评估格列美脲对骨骼系统的影响。还研究了骨量、矿物质含量、钙和磷含量以及血清雌激素、骨钙素和大鼠抗酒石酸酸性磷酸酶水平。
去卵巢大鼠的雌激素缺乏导致骨重塑增加，骨吸收和形成加剧以及矿化受损。去卵巢大鼠中的格列美脲抑制了雌激素缺乏引起的骨骼系统变化的发展，增强了骨形成。在有雌激素存在的情况下（未去卵巢大鼠），格列美脲也增强了骨形成，但程度较小。
在绝经后女性2型糖尿病的治疗中，格列美脲可能对骨重塑有有益作用，并可能降低骨质疏松症发生的风险。
