El-Nabarawi Naglaa, El-Wakd Mohamed, Salem Mostafa
Faculty of Medicine, National Egyptian Center of Environmental and Toxicological Research.
Rheumatology and Rehabilitation Department.
Drug Des Devel Ther. 2017 May 2;11:1383-1391. doi: 10.2147/DDDT.S133020. eCollection 2017.
The aim of this study was to evaluate the effect of atorvastatin on the bone formation and resorption markers in ovariectomized rats (experimental study), and to study its effect on the bone mineral density (BMD) in postmenopausal osteoporotic women (clinical study).
The study involved experimental and clinical aspects. In the experimental aspect, 42 female Wistar rats were divided into five groups: Group I (n=6; sham-operated), Group II (n=6; 1 mL of carboxymethyl cellulose [CMC] was administered orally), Group III (n=6; 20 mg/kg orally of atorvastatin was administered), Group IV (n=12; untreated ovariectomized [OVX] rats and served as a model of osteoporosis [OP]) and Group V (n=12; 20 mg/kg orally of atorvastatin was administered to ovariectomized rats). After 4 weeks, serum acid phosphatase, alkaline phosphatase, osteocalcin, total calcium and inorganic phosphorus were assessed. Then, 3 µm thickness lumbar and femur sections were examined using a light microscope to assess cortical thickness, trabecular area, numbers of osteoblasts and osteoclasts. In the clinical aspect, 85 post-menopausal osteoporotic females with recently detected hyperlipidemia participated in the study. Atorvastatin 40 mg/day, calcium carbonate 500 mg/day and vitamin D 800 international units were given to all patients for a period of 18 months. BMD was measured at the start and at the end of the study by dual-energy X-ray absorptiometry (DEXA).
In the experiment aspect, the biomarkers of bone remodeling were notably elevated in the OVX group. Administration of atorvastatin produced a significant decrease in the level of these bone metabolic markers. Atorvastatin significantly ameliorates osteoporotic changes induced by ovariectomy. In the clinical aspect, after 18 months the DEXA showed improvement in the T-score for the three measured zones; however, these changes were statistically significant only in the femoral neck area.
Atorvastatin was able to decrease the rate of bone metabolism and increase osteogenic activity. It has dual mode of action; both anabolic and antiresorptive effect on bone. This lipophilic statin member may act as a double weapon drug.
本研究旨在评估阿托伐他汀对去卵巢大鼠骨形成和骨吸收标志物的影响(实验研究),并研究其对绝经后骨质疏松女性骨密度(BMD)的影响(临床研究)。
本研究涉及实验和临床两个方面。在实验方面,将42只雌性Wistar大鼠分为五组:第一组(n = 6;假手术组),第二组(n = 6;口服1 mL羧甲基纤维素[CMC]),第三组(n = 6;口服20 mg/kg阿托伐他汀),第四组(n = 12;未治疗的去卵巢[OVX]大鼠,作为骨质疏松症[OP]模型)和第五组(n = 12;给去卵巢大鼠口服20 mg/kg阿托伐他汀)。4周后,评估血清酸性磷酸酶、碱性磷酸酶、骨钙素、总钙和无机磷。然后,使用光学显微镜检查3 µm厚的腰椎和股骨切片,以评估皮质厚度、小梁面积、成骨细胞和破骨细胞数量。在临床方面,85名最近检测出高脂血症的绝经后骨质疏松女性参与了本研究。所有患者均给予阿托伐他汀40 mg/天、碳酸钙500 mg/天和维生素D 800国际单位,为期18个月。在研究开始和结束时通过双能X线吸收法(DEXA)测量骨密度。
在实验方面,OVX组骨重塑的生物标志物显著升高。给予阿托伐他汀可使这些骨代谢标志物的水平显著降低。阿托伐他汀可显著改善去卵巢诱导的骨质疏松变化。在临床方面,18个月后,DEXA显示三个测量区域的T值有所改善;然而,这些变化仅在股骨颈区域具有统计学意义。
阿托伐他汀能够降低骨代谢率并增加成骨活性。它具有双重作用模式;对骨具有合成代谢和抗吸收作用。这种亲脂性他汀类药物可能是一种双效药物。