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Endocrine

, Volume 60, Issue 1, pp 138–150 | Cite as

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

  • Mostafa Shahrezaee
  • Ahmad Oryan
  • Farshid Bastami
  • Sepanta Hosseinpour
  • Mohammad Hossein Shahrezaee
  • Amir Kamali
Original Article

Abstract

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 < 0.05). The results of different analysis also indicated that there was no statistical difference between the atorvastatin-treated animals and the negative control. Among all treatments, only atorvastatin showed an evident hepatotoxicity and myopathy.

Conclusions

It was concluded that the lovastatin and simvastatin efficiently ameliorated the OVX-induced osteoporosis. Moreover, the simvastatin-treated animals showed more resemblance to the normal group in terms of BMD, expression of osteogenic genes, serum biochemical parameters, histomorphometric findings, and biomechanical performance with no significant side-effects.

Keywords

Osteoporosis Simvastatin Lovastatin Atorvastatin Systemic drug delivery OVX rat 

Notes

Acknowledgements

The authors would like to thank Dr. Ali Moshiri for sharing his pearls of wisdom with us during the course of this research.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Orthopedic Surgery, School of MedicineAJA University of Medical ScienceTehranIran
  2. 2.Department of Pathology, School of Veterinary MedicineShiraz UniversityShirazIran
  3. 3.Dental Research Center, Research Institute of Dental Sciences, School of DentistryShahid Beheshti University of Medical SciencesTehranIran
  4. 4.School of Advanced Technologies in MedicineShahid Beheshti University of Medical SciencesTehranIran
  5. 5.School of DentistryTehran University of Medical SciencesTehranIran

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