Histomorphometric Analysis: Effects of Simvastatin on Bone Mass, Microarchitecture and Turnover in Normal Rat

Abstract:

Simvastatin, as one of the HMG-CoA reductase inhibitors for lowering lipids, has been demonstrated its potential benefit in bone formation, which was, however, conflicting and inconclusive in vivo studies. Thus, we performed this study to assess the in vivo effects of simvastatin on bone formation. Six-week old rats were administered with simvastatin (20 mg/kg/d) or vehicle for 6 or 9 weeks. All animals were sacrificed one day after the final administration. The left femora were removed for the measurement of bone histomorphometry and bone mineral density (BMD).Compared to the control groups, on both 6th week and 9th week, bone mineral density and bone histomorphometry detected no significant differences in bone mass and microarchitecture in simvastatin treatment group, as well as bone formatin/resorption parameters. These results indicate that simvastatin had no positive effect or impact on bone in rats administered with high dose simvastatin (20 mg/kg/d) for 6 or 9 weeks.

• Periodical: Applied Mechanics and Materials (Volume 302)
• Pages: 26-30
• DOI: https://doi.org/10.4028/www.scientific.net/AMM.302.26
• Online since: February 2013
• Authors: Fa Ming Tian, Liu Zhang, Hui Zhang, Jie Zheng, Da Cheng Han, Fang Yang
• Keywords: Bone Formation, Bone Histomorphometry, Bone Mineral Density, Bone Resorption, Simvastatin

References

[1] Mundy G, Garrett R, Harris S, Chan J, Chen D, Rossini G, Boyce B, Zhao M, and Gutierrez G, Stimulation of bone formation in vitro and in rodents by statins, Science . 286(1999) 1946-(1949).

DOI: 10.1126/science.286.5446.1946

[2] Wang EA, Rosen V, D'Alessandro JS, Bauduy M, Cordes P, Harada T, Israel DI, Hewick RM, Kerns KM and LaPan P, Recombinant human bone morphogenetic protein induces bone formation, Proc Natl Acad Sci USA . 87(1990)2220–2224.

DOI: 10.1073/pnas.87.6.2220

[3] Deng ZL, Sharff KA, Tang N, Song WX, Luo J, Luo X, Chen J, Bennett E, Reid R, Manning D, Xue A, Montag AG, Luu HH, Haydon RC and He TC. Regulation of osteogenic differentiation during skeletal development, Front Biosci. 13(2008)2001 -(2021).

[4] Maritz FJ, Conradie MM, Hulley PA, Gopal R and Hough S, Effect of statins on bone mineral density and bone histomorphometry in rodents, Arterioscler Thromb Vasc Biol. 21(2001) 1636- 1641.

DOI: 10.1161/hq1001.097781

[5] Corsino A, Bellosta S, Baetta R, Fumagalli R, Paoletti R and Bernini F, New insights into the pharmacodynamic and pharmacokinetic properties of statins, Pharmacol Ther. 84(1999) 413-428.

DOI: 10.1016/s0163-7258(99)00045-5

[6] Reinoso RF, SanchezNavarro A, Garcia MJ and Prous JR, Preclinical pharmacokinetics of statins, Methods Fin Clin Pharmacol. 24(2002) 593-613.

DOI: 10.1358/mf.2002.24.9.802312

[7] William D and Feely J, Pharmacokinetic-pharmacodynamic drug interaction with HMG-CoA reductase inhibitors, Clin Pharmacokinet. 41(2002) 343-370.

DOI: 10.2165/00003088-200241050-00003

[8] Oxlund H and Andreassen TT: Simvastatin treatment partially prevents ovariectomy-induced bone loss while increasing cortical bone formation, Bone. 34( 2004)609-618.

DOI: 10.1016/j.bone.2003.12.014

[9] Saraf SK, Singh A, Garbyal RS and Singh V, Effect of simvastatin on fracture healing-an experimental study. Indian J Exp Biol . 45( 2007)444-449.

[10] Seto H, Ohba H, Tokunaga K, Hama H, Horibe M and Nagata T, Topical administration of simvastatin recovers alveolar bone loss in rats, J Periodontal Res. 43(2008)261-267.

DOI: 10.1111/j.1600-0765.2007.01024.x

[11] Patil S, Holt G, Raby N, McLellan AR, Smith K, O'Kane S, Beastall G and Crossan JF, Prospective, double blind, randomized, controlled trial of simvastatin in human fracture healing, J Orthop Res. 27(2009)281-285.

DOI: 10.1002/jor.20572

[12] Chissas D, Stamatopoulos G, Verettas D, Kazakos K, Papalois A, Agrogiannis G, Papaeliou A, Agapitos E, Balanika A, Papadopoulou E, Anastopoulos G, Ntagiopoulos PG and Asimakopoulos A, Can low doses of simvastatin enhance fracture healing? An experimental study in rabbits, Injury. 41(2009).

DOI: 10.1016/j.injury.2009.07.024

[13] Pauly S, Luttosch F, Morawski M, Haas NP, Schmidmaier G, Wildemann B, simvastatin locally applied from biodegradable coating of osteosynthetic implants in improves fracture healing coparable to BMP-2 application, Bone. 45(2009)505-511.

DOI: 10.1016/j.bone.2009.05.010

[14] Fukui T, Ii M, Shoji T, Matsumoto T, Mifune Y, Kawakami Y, Akimaru H, Kawamoto A, Kuroda T, Saito T, Tabata Y, Kuroda R, Kurosaka M, Asahara T, Therapeutic effect of local administration of low dose simvastatin-conjugated gelatin hydrogel for fracture healing, J Bone Miner Res. 2012 [Epub ahead of print].

DOI: 10.1002/jbmr.1558