The effect of atorvastatin, 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor (HMG-CoA), on the prevention of osteoporosis in ovariectomized rabbits.
Osteoporosis is a most frequent systemic skeletal disease characterized as low bone mineral density and microarchitectural deterioration of bone tissue, resulting in increased bone fragility and fracture risk. Although several drugs such as bisphosphonates, estrogen replacement treatment, and selective estrogen receptor modulators have been used to treat osteoporosis, all these are not the ideal drugs because of insufficient curative ability and adverse side effects. Recently, atorvastatin has ordinarily been prescribed as an anti-hyperlipidemia drug, not as an anti-osteoporosis drug. However, its clinical outcome and potential treatment mechanism are still unclear. In this study, the bilateral ovariectomy of rabbits was duplicated to develop osteoporosis animal model. The effect of atorvastatin on in vivo was determined, and the functional mechanism was studied in vitro after the curative effect was explored. Atorvastatin was observed to significantly increase the mechanical parameters such as maximum load, stiffness, and energy-absorbing capacity, and it improved the microarchitecture. The anti-osteoporosis activity of atorvastatin may be the result of the promotion of differentiation of osteoblasts by inducing synthesis of vascular endothelial growth factor, bone morphogenetic protein 2 (BMP2), core-binding factor alpha 1 (CBFα1), and inhibition of osteoclast formation through the osteoprotegerin (OPG)-receptor activator for the nuclear factor κB ligand (RANKL) system. Our study observations give reliable experimental evidence for clinical application of atorvastatin to treat the disorder of osteoporosis.
Institution of National Drug Clinical Trial, the First Affiliated Hospital of Bengbu Medical College, No. 287 Changhuai Road, Bengbu, 233004, China.
Huan
H
Zhou
Intensive Care Unit, the First Affiliated Hospital of Bengbu Medical College, Bengbu, 233004, China.
Yunqiu
Y
Xie
Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming, China.
Zulqarnain
Z
Baloch
Department of Pharmacy, the First Affiliated Hospital of Bengbu Medical College, Bengbu, 233004, China.
Qingping
Q
Shi
Department of Pharmacy, Bengbu Medical College, Bengbu, 233004, China.
Qiang
Q
Huo
Institution of National Drug Clinical Trial, the First Affiliated Hospital of Bengbu Medical College, No. 287 Changhuai Road, Bengbu, 233004, China. mataobb@sina.com.|Department of Pharmacy, Bengbu Medical College, Bengbu, 233004, China. mataobb@sina.com.
Tao
T
Ma
D000818:Animals; D000069059:Atorvastatin / Q000494:pharmacology / Q000627:therapeutic use*; D015519:Bone Density / Q000187:drug effects; D002460:Cell Line; D005260:Female; D005269:Femur / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D021621:Imaging, Three-Dimensional; D008159:Lumbar Vertebrae / Q000187:drug effects / Q000473:pathology; D051379:Mice; D010024:Osteoporosis / Q000097:blood / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000517:prevention & control*; D053244:Osteoprotegerin / Q000235:genetics / Q000378:metabolism; D010052:Ovariectomy; D053245:RANK Ligand / Q000235:genetics / Q000378:metabolism; D011817:Rabbits
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D053244:Osteoprotegerin; D053245:RANK Ligand; D000069059:Atorvastatin
Atorvastatin; Osteoblasts; Osteoclasts; Osteoporosis; Ovariectomy