Simvastatin improves spinal fusion in rats

Conclusion: Our results suggest that simvastatin can promote spinal fusion and can be used as an adjunct to spinal fusion procedures in an elderly population with high cholesterol levels.

📌 3 Key Takeaways

🎯

Objective & Hypothesis:Objective: Statins stimulate bone formation by inducing the expression of bone morphogenetic proteins (BMP-2).

📊

Key Findings & Data:Methods: Twenty rats were randomized into a spinal fusion group (SF) (n=10) or a spinal fusion and oral simvastatin administered group (SFS) (n=10).

💡

Conclusion & Impact:Conclusion: Our results suggest that simvastatin can promote spinal fusion and can be used as an adjunct to spinal fusion procedures in an elderly population with high cholesterol levels.

🔬Design:Research Article

📍Scope:Comprehensive Sample

⚙️Variables:Psödoartroz · Omurilik füzyonu · Sıçan

Abstract

Objective: Statins stimulate bone formation by inducing the expression of bone morphogenetic proteins (BMP-2). The aim of our study was to investigate the effects of orally administered sim vastatin on spinal fusion in rats. Methods: Twenty rats were randomized into a spinal fusion group (SF) (n=10) or a spinal fusion and oral simvastatin administered group (SFS) (n=10). A spinal fusion was performed between L4-L6 representing two levels. Simvastatin (120 mg/kg/day) was administered orally in the SFS group. The rats were killed at the end of the 12 week study period. Results: Manual palpation revealed two moderate fusions in the SF group. The SFS group did not reveal any signs of pseudoarthrosis. An average three-point bending force causing failure of fusion revealed results of 148.80±39.403 Newtons and 123.80±28.479 Newtons in SFS and SF groups, respectively (p>0.05). Histological examination revealed better fusion grades in the SFS group (mean: 9.30±0.949) than in the SF group (mean: 6.80±2.044) (p=0.003). Radiographic examination revealed Grade C fusion in two levels and Grade A fusion in 18 levels in the SF group. In the SFS group, Grade C fusion was detected in one level and Grade A fusions in 19. Conclusion: Our results suggest that simvastatin can promote spinal fusion and can be used as an adjunct to spinal fusion procedures in an elderly population with high cholesterol levels.

Özet

Amaç: Statinler kemik morfogenetik proteinlerinin (BMP-2) üretimini uyararak kemik oluşumuna katkıda bulunurlar. Çalışmamızda, sıçanlarda ağız yoluyla simvastatin alımının spinal füzyon üzerine olan etkilerini araştırmayı hedefledik. Çalışma planı: Yirmi adet sıçan spinal füzyon grubu (SF; n=10) ve spinal füzyon ve simvastatin grubu (SFS; n=10) olarak rastgele iki gruba bölündü. L4-L6 arasına (her sıçanda toplam 2 se¬viye) spinal füzyon modeli uygulandı. Simvastatin 120 mg/kg/gün dozunda SFS grubundaki sıçanlara ağız yoluyla verildi. Sıçanlar 12. hafta sonunda öldürüldü. Bulgular: Elle muayenede SF grubunda 2 orta dereceli füzyon tespit edilirken, SFS grubunda psödoartroz görülmedi. Ortalama 3 nokta eğme testi ile füzyonda yetmezlik oluşturan değerler SFS ve SF gruplarında, sırasıyla, 148.80±39.403 Newton ve 123.80±28.479 Newton olarak tespit edildi (p>0.05). Histolojik skorlamalarda SFS grubunda ortalama 9.30 ±0.949 değerle SF grubundan (ortalama: 6.80±2.044) daha iyi sonuçlar elde edildi (p=0.003). Radyolojik değerlendirmede SF grubunda 2 seviyede Derece C ve 18 seviyede Derece A füzyon tespit edilirken, SFS grubunda 1 seviyede Derece C ve 19 seviyede Derece A füzyon tespit edildi. Çıkarımlar: Sonuçlarımız simvastatinin spinal füzyona katkıda bulunabileceğini ve yüksek kolesterollü yaşlı hastalarda spinal füzyon girişimlerinde ek ilaç olarak kullanılabileceğini önermektedir.

Keywords

Psödoartroz Omurilik füzyonu Sıçan Sprague-Dawley Hidroksimetilglutaril CoA redüktaz inhibitörleri Simvastatin Hayvanlar Kemik morfogenetik protein 2 Kemik oluşumu Lumbar omurga İlaç uygulama oral Pseudarthrosis Spinal Fusion Rats Hydroxymethylglutaryl-CoA Reductase Inhibitors Animals Bone Morphogenetic Protein 2 Osteogenesis Lumbar Vertebrae Administration Oral

🔖

Cite This Article

BOSTAN, B., GÜNEŞ, T., AŞÇI, M., ŞEN, C., KELEŞTEMUR, M. H., ERDEM, M., KÖSEOĞLU, R. D., ERKORKMAZ, Ü. (2011). Simvastatin improves spinal fusion in rats. Acta Orthopaedica et Traumatologica Turcica, Cilt: 45 - Sayı: 4, 270–275. https://ajindex.com/articles/354090

References (16)

Garrett IR, Gutierrez G, Mundy GR. Statins and bone for mation. Curr Pharm 2001;7:715-36
Deedwania PC, Hunninghake DB, Bays HE, Jones PH, Cain VA, Blasetto JW; STELLAR Study Group. Effects of rosuvastatin, atorvastatin, simvastatin, and pravastatin on atherogenic dyslipidemia in patients with characteristics of the metabolic syndrome. Am J Cardiol 2005;95:360-6
Oxlund H, Andreassen TT. Simvastatin treatment partial ly prevents ovariectomy-induced bone loss while increas ing cortical bone formation. Bone 2004;34:609-18
Mundy G, Garrett R, Harris S, Chan J, Chen D, Rossini G, Boyce B, Zhao M, Gutierrez G. Stimulation of bone for mation in vitro and in rodents by statins. Science 1999; 286:1946-9
Wong RW, Rabie AB. Early healing pattern of statin induced osteogenesis. Br J Oral Maxillofac Surg 2005;43: 46-50
Drespe IH, Polzhofer GK, Turner AS, Grauer JN. Animal models for spinal fusion. Spine J 2005;5:209-16
Dimar JR 2nd, Ante WA, Zhang YP, Glassman SD. The effects of nonsteroidal anti-inflammatory drugs on poste rior spinal fusions in the rat. Spine 1996;21:1870-6
Lenke LG, Bridwell KH, Bullis D, Betz RR, Baldus C, Schoenecker PL. Results of in situ fusion for isthmic spondylolisthesis. J Spinal Disord 1992;5:433-42
Huddlestone PM, Steckelberg JM, Hansen AD, Rouse MS, Bolander ME, Pater R. Ciprofloxacin inhibition of experimental fracture healing. J Bone Joint Surg Am 2000;82:161-73
Moazzaz P, Gupta MC, Gilotra MM, Gilotra MN, Maitra S, Theerajunyaporn T, et al. Estrogen-dependent actions of bone morphogenetic protein-7 on spine fusion in rats. Spine 2005;30:1706-11
Salamon ML, Althausen PL, Gupta MC, Laubach J. The effects of BMP-7 in a rat posterolateral intertransverse process fusion model. J Spinal Disord Tech 2003;16:90-5
Guizzardi S, Di Silvestre M, Scandroglio R, Rugerri A, Savini R. Implants of heterologous demineralized bone matrix for induction of posterior spinal fusion in rats. Spine 1992;17:701-7
Patel TC, Erulkar JS, Grauer JN, Toriano NW, Panjabi MM, Friedlaender GE. Osteogenic protein-1 overcomes the inhibitory effect of nicotine on posterolateral lumbar fusion. Spine 2001;26:1656-61
Maeda T, Kawane T, Horiuchi N. Statins augment vascu lar endothelial growth factor expression in osteoblastic cells via inhibition of protein prenylation. Endocrinology 2003;144:681-92
Edwards CJ, Spector TD. Statins as modulators of bone formation. Arthritis Res 2002;4:151-3
Gonyeau MJ. Statin