The effects of locally applied simvastatin on an experimental mouse femur nonunion model

Objective: The aim of this study was to assess the effects of locally applied simvastatin on femur nonunions in a mouse model. Methods: The study included 32 male Wistar albino mice randomly allocated to one of four groups: two control groups (control-4 week [C4w] and control-8 week (C8w)] and two treatment groups (simvastatin-4 week [S4w] and simvastatin-8 week [S8w]). The control groups received dimethylsulfoxide locally injected at a dose of 10 mg/kg/day after surgical intervention for 1 week. Treatment groups received a liquefied form of simvastatin locally to the osteotomy field by injection at a dose of 10 mg/ kg/day, starting from the first postoperative day for 1 week. The C4w and S4w groups were sacrificed 4 weeks and the C8w and S8w groups 8 weeks after the end of local treatment. Before sacrifice, intracardiac blood samples were retrieved for biochemical analysis and radiographies were taken. The right femurs of mice were then removed for histopathological evaluation. Results: There were significant differences between the control and treatment groups when evaluated radiologically. Significantly higher levels of bone-specific alkaline phosphatase and osteocalcin values were found in the treatment groups than in the controls (p<0.05). Conclusion: According to biochemical, radiological and histopathological results, local application of simvastatin appears to produce beneficial effects on the mouse femur nonunion model.

___

1. Einhorn TA. The cell and molecular biology of fracture healing. Clin Orthop Relat Res 1998;(355 Suppl):7-21.

2. LaVelle DG. Delayed union and nonunion of fractures. In: Canale ST, editor. Campbell’s Operative Orthopaedics. 10th ed. Philadelphia, PA: Mosby Publishers; 2003. p. 3126.

3. Serin-Kilicoglu S, Erdemli E. New addition to the statin’s effect. J Trauma 2007;63:187-91.

4. Human JA, Ubbink JB, Jerling JJ, Delport R, Vermaak WJ, Vorster HH, et al. The effect of Simvastatin on the plasma antioxidant concentrations in patients with hypercholesterolaemia. Clin Chim Acta 1997;263:67-77.

5. Ferro D, Parrotto S, Basili S, Alessandri C, Violi F. Simvastatin inhibits the monocyte expression of proinflammatory cytokines in patients with hypercholesterolemia. J Am Coll Cardiol 2000;36:427-31.

6. van Nieuw Amerongen GP, Vermeer MA, Nègre-Aminou P, Lankelma J, Emeis JJ, van Hinsbergh VW. Simvastatin improves disturbed endothelial barrier function. Circulation 2000;102:2803-9.

7. Gutierrez GE, Lalka D, Garrett IR, Rossini G, Mundy GR. Transdermal application of lovastatin to rats causes profound increases in bone formation and plasma concentrations. Osteoporos Int 2006;17:1033-42.

8. Mundy G, Garrett R, Harris S, Chan J, Chen D, Rossini G, et al. Stimulation of bone formation in vitro and in rodents by statins. Science 1999;286:1946-9.

9. Price CP, Thompson PW. The role of biochemical tests in the screening and monitoring of osteoporosis. Ann Clin Biochem 1995;32:244-60.

10. Lee AJ, Hodges S, Eastell R. Measurement of osteocalcin. Ann Clin Biochem 2000;37:432-46.

11. Eastell R. Assessment of bone density and bone loss. Osteoporos Int 1996;6 Suppl 2:3-5.

12. Garcia P, Holstein JH, Maier S, Schaumlöffel H, Al-Marrawi F, Hannig M, et al. Development of a reliable nonunion model in mice. J Surg Res 2008;147:84-91.

13. Goldberg VM, Powell A, Shaffer JW, Zika J, Bos GD, Heiple KG. Bone grafting: role of histocompatibility in transplantation. J Orthop Res 1985;3:389-404.

14. Huo MH, Troiano NW, Pelker RR, Gundberg CM, Friedlaender GE. The influence of ibuprofen on fracture repair: biomechanical, biochemical, histologic, and histomorphometric parameters in rats. J Orthop Res 1991;9:383-90.

15. Wang JW, Xu SW, Yang DS, Lv RK. Locally applied simvastatin promotes fracture healing in ovariectomized rat. Osteoporos Int 2007;18:1641-50.

16. Skoglund B, Aspenberg P. Locally applied Simvastatin improves fracture healing in mice. BMC Musculoskelet Disord 2007;8:98.

17. Fukui T, Ii M, Shoji T, Matsumoto T, Mifune Y, Kawakami Y, et al. Therapeutic effect of local administration of low-dose simvastatin-conjugated gelatin hydrogel for fracture healing. J Bone Miner Res 2012;27:1118-31.

18. Ayukawa Y, Yasukawa E, Moriyama Y, Ogino Y, Wada H, Atsuta I, et al. Local application of statin promotes bone repair through the suppression of osteoclasts and the enhancement of osteoblasts at bone-healing sites in rats. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2009;107:336-42.

19. Wang PS, Solomon DH, Mogun H, Avorn J. HMG-CoA reductase inhibitors and the risk of hip fractures in elderly patients. JAMA 2000;283:3211-6.

20. Edwards CJ, Hart DJ, Spector TD. Oral statins and increased bone-mineral density in postmenopausal women. Lancet 2000;355:2218-9.

21. Chan KA, Andrade SE, Boles M, Buist DS, Chase GA, Donahue JG, et al. Inhibitors of hydroxymethylglutarylcoenzyme A reductase and risk of fracture among older women. Lancet 2000;355:2185-8.

22. Chung YS, Lee MD, Lee SK, Kim HM, Fitzpatrick LA. HMG-CoA reductase inhibitors increase BMD in type 2 diabetes mellitus patients. J Clin Endocrinol Metab 2000;85:1137-42.

23. Wada Y, Nakamura Y, Koshiyama H. Lack of positive correlation between statin use and bone mineral density in Japanese subjects with type 2 diabetes. Arch Intern Med 2000;160:2865.

24. van Staa TP, Wegman S, de Vries F, Leufkens B, Cooper C. Use of statins and risk of fractures. JAMA 2001;285:1850-5.

25. LaCroix AZ, Cauley JA, Pettinger M, Hsia J, Bauer DC, McGowan J, et al. Statin use, clinical fracture, and bone density in postmenopausal women: results from the Women’s Health Initiative Observational Study. Ann Intern Med 2003;139:97-104.

26. von Stechow D, Fish S, Yahalom D, Bab I, Chorev M, Müller R, et al. Does simvastatin stimulate bone formation in vivo? BMC Musculoskelet Disord 2003;4:8.

27. Garrett IR, Gutierrez GE, Rossini G, Nyman J, McCluskey B, Flores A, et al. Locally delivered lovastatin nanoparticles enhance fracture healing in rats. J Orthop Res 2007;25:1351-7.

28. Rosenson RS, Tangney CC, Langman CB, Parker TS, Levine DM, Gordon BR. Short-term reduction in bone markers with high-dose simvastatin. Osteoporos Int 2005;16:1272-6.
Acta Orthopaedica et Traumatologica Turcica-Cover
  • ISSN: 1017-995X
  • Başlangıç: 2015
  • Yayıncı: Türk Ortopedi ve Travmatoloji Derneği
Sayıdaki Diğer Makaleler

Analysis of the complications of the collum femoris preserving (CFP) prostheses

Mingqing LI, Yihe HU, Jie XIE

Degenerative changes in the interspinous ligament

Jian-Feng ZHANG, Chao LIU, He-Jun YU, Jian-Jun MA, Hong-Xin CAI, Shun-Wu FAN

The effects of locally applied simvastatin on an experimental mouse femur nonunion model

Atilla KOÇER, Mithat ÖNER, İBRAHİM KARAMAN, Derya KOÇER, İBRAHİM HALİL KAFADAR, AHMET GÜNEY, Zehra Filiz KARAMAN

Isolated foot metastasis of squamous cell carcinoma of the lung: a rare location

GÖKHAN KAYNAK, Enis YILDIRIM, Hüseyin BOTANLIOĞLU, Tahir ÖĞÜT

Influence of number and orientation of screws on stability in the internal fixation of unstable femoral neck fractures

Seyit Ali GÜMÜŞTAŞ, Hacı Bayram TOSUN, İSMAİL AĞIR, Mehmet Müfit ORAK, Tolga ONAY, GÜVENİR OKCU

Effects of circulating endothelial progenitor cells, serum vascular endothelial growth factor and hypogammaglobulinemia in Perthes disease

HİCABİ SEZGİN, Birol GÜLMAN, ALPER ÇIRAKLI, Abdülkerim BEDİR, Dilek USTA, HÜSEYİN SİNA COŞKUN, ALİŞAN YILDIRAN

The complete type of suprapatellar plica and lipoma arborescens: a case report

MEHMET ERDURAN, GÖKHAN MERİÇ, ALİ ENGİN ULUSAL, Devrim AKSEKİ

Pseudomonas osteomyelitis of the proximal humerus after arthroscopic rotator cuff repair

NURİ AYDIN, EVRİM ŞİRİN, AHMET NADİR AYDEMİR, Gökhan ZENGİN

Diabetic hand infections and hyperbaric oxygen therapy

Figen AYDIN, Ahmet KAYA, Ahmet SAVRAN, Mustafa İNCESU, Cengiz KARAKUZU, ANIL MURAT ÖZTÜRK

Comparison of platelet-rich plasma and steroid injection in the treatment of plantar fasciitis

FERHAT SAY, Deniz GÜRLER, Erkan İNKAYA, Murat BÜLBÜL