Comparative impact of systemic delivery of atorvastatin, simvastatin, and lovastatin on bone mineral density of the ovariectomized rats

Purpose In addition to lipid-lowering properties, statins have been suggested to affect bone turnover by increasing the osteoblastic bone formation and blocking the osteoclastogenesis. However, there are many controversial reports regarding the beneficial effect of statins on osteoporosis. In this s...

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Bibliographic Details
Published in:Endocrine 2018-04, Vol.60 (1), p.138-150
Main Authors: Shahrezaee, Mostafa, Oryan, Ahmad, Bastami, Farshid, Hosseinpour, Sepanta, Shahrezaee, Mohammad Hossein, Kamali, Amir
Format: Article
Language:English
Subjects:
Animals
Atorvastatin
Atorvastatin - pharmacology
Biochemical analysis
Biomechanics
Bone density
Bone Density - drug effects
Bone growth
Bone mineral density
Bone turnover
Bones
Calcium
Calcium (blood)
Computed tomography
Diabetes
Endocrinology
Female
Femur - diagnostic imaging
Femur - drug effects
Hepatotoxicity
Humanities and Social Sciences
Hydroxymethylglutaryl-CoA Reductase Inhibitors - pharmacology
Internal Medicine
Lipophilic
Lovastatin
Lovastatin - pharmacology
Mechanical properties
Medicine
Medicine & Public Health
multidisciplinary
Myopathy
Original Article
Osteoblasts
Osteoclastogenesis
Osteogenesis
Osteoporosis
Ovariectomy
Rats
Rats, Sprague-Dawley
Rhabdomyolysis
Rodents
Science
Simvastatin
Simvastatin - pharmacology
Statins
Statistical analysis
Statistics
X-Ray Microtomography
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Summary:Purpose In addition to lipid-lowering properties, statins have been suggested to affect bone turnover by increasing the osteoblastic bone formation and blocking the osteoclastogenesis. However, there are many controversial reports regarding the beneficial effect of statins on osteoporosis. In this study, we investigated the therapeutic effects of the most important lipophilic statins administered orally for 60 days to the ovariectomized (OVX) female Sprague–Dawley rats and compared the effects on different harvested trabecular and compact bones. Methods Thirty female rats were divided into five equal groups including the normal rats, untreated OVX rats (negative control), and the OVX rats treated with atorvastatin (20 mg/kg/day), simvastatin (25 mg/kg/day), and lovastatin (20 mg/kg/day). The osteoporotic animals were treated daily for 60 days and euthanized at the end of experiments. The effectiveness of these treatments was evaluated by biomechanical testing, histopathologic, histomorphometric, micro-CT scan, real-time PCR, and serum biochemical analysis. Moreover, the hepatotoxicity and rhabdomyolysis related with these treatments were assessed by biochemistry analysis and histopathological evaluation. Results The results and statistical analysis showed that systemic delivery of simvastatin and lovastatin significantly increased serum calcium level, expression of osteogenic genes, bone mineral density (BMD), and biomechanical properties in comparison to the untreated OVX rats, especially in trabecular bones ( P  
ISSN:1355-008X
1559-0100
DOI:10.1007/s12020-018-1531-6