The use of simvastatin with aromasin in an ovariectomized rat model: effects on the skeletal system.
BACKGROUND
Many studies have reported the positive effect on bones of statins that inhibit the action of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase and suppress hepatic cholesterol biosynthesis. Recent data suggest that statins used in the treatment of hypercholesterolemia decrease fracture risk and increase bone mineral density (BMD). Aromasin (an aromatase inhibitor) is an effective and well-tolerated drug used in endocrine therapy for the treatment of hormone-sensitive early breast cancer in postmenopausal patients. It has a catabolic effect on the skeletal system and can therefore significantly increase the incidence of fractures. Our study aims to determine the effects of Aromasin and simvastatin plus Aromasin on the BMD in an ovariectomized rat model.


METHODS
In total, 27 female Sprague Dawley rats were subjected to a bilateral oophorectomy. One month after the oophorectomy, the rats were divided into the following 3 groups: (1) The control group, in which water was administered; (2) the Aromasin group in which Aromasin was administered orally; and (3) the Aromasin plus simvastatin group in which a combination of Aromasin and simvastatin was administered orally. The BMD of the lumbar spine (L1-L5) and left femoral bone was measured using dual-energy X-ray absorptiometry (DXA) 1 month after the ovariectomy and 3 months after treatment began. Blood was drawn at the time of oophorectomy and 3 months after treatment began to check the levels of calcium, phosphorus, and alkaline phosphatase (alk-ptase).


RESULTS
In the Aromasin plus simvastatin group, the BMD of both the lumbar spine (p=0.003) and the left femoral bone (p=0.001) increased significantly after 3 months of treatment. In comparison with the Aromasin group, the Aromasin plus simvastatin group showed a significant increase in the BMD of both the lumbar spine and the left femoral bone (p=0.04 and p=0.005 respectively). In the Aromasin group, the BMD of the left femoral bone (p=0.01) and that of the lumbar spine both decreased significantly (p=0.001). The calcium, phosphorus, and alk-ptase levels were not significantly different among the 3 groups.


CONCLUSIONS
In the Aromasin group, catabolic effects on the skeletal system were observed. In the Aromasin plus simvastatin group, the BMD significantly increased. Thus statins may have therapeutic application in the treatment of osteoporosis using Aromasin since they can counterbalance the adverse effects of this drug.
Chen
Sung-Hsiung
SH
Department of Orthopaedic Surgery, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan.
Chou
Fong-Fu
FF
Ko
Jih-Yang
JY
D000730:Androstadienes / Q000008:administration & dosage / Q000009:adverse effects*; D000818:Animals; D047072:Aromatase Inhibitors / Q000009:adverse effects*; D015519:Bone Density / Q000187:drug effects*; D004195:Disease Models, Animal; D005260:Female; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D010052:Ovariectomy; D051381:Rats; D017207:Rats, Sprague-Dawley; D019821:Simvastatin / Q000008:administration & dosage / Q000494:pharmacology*
D000730:Androstadienes; D047072:Aromatase Inhibitors; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D019821:Simvastatin; C056516:exemestane