Single-dose local simvastatin injection improves implant fixation via increased angiogenesis and bone formation in an ovariectomized rat model

Medical Science Monitor

Volumn 21, Issue , 2015, Pages 1428-1439

  Tan, Jie ^a,b   Yang, Ning ^a   Fu, Xin ^a,b   Cui, Yueyi ^a   Guo, Qi ^a   Ma, Teng ^a   Yin, Xiaoxue ^a,b   Leng, Huijie ^a,b   Song, Chunli ^a,b  

^a PEKING UNIVERSITY THIRD HOSPITAL   (China)

^b Beijing Key Laboratory of Emerging Infectious Diseases   (China)

Author keywords

Angiogenesis inducing agents; Osseointegration; Osteoporosis; Simvastatin

Indexed keywords

BONE MORPHOGENETIC PROTEIN 2; BOVINE SERUM ALBUMIN; CD31 ANTIGEN; DIMETHYL SULFOXIDE; SILICONE; SIMVASTATIN; VASCULOTROPIN; VASCULOTROPIN RECEPTOR 2; VON WILLEBRAND FACTOR; BMP2 PROTEIN, RAT; VASCULAR ENDOTHELIAL GROWTH FACTOR A, RAT; VASCULOTROPIN A;

ANGIOGENESIS; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BONE DENSITY; BONE DEVELOPMENT; BONE MASS; BONE REGENERATION; BONE SCREW; CALCIFICATION; CONTROLLED STUDY; CORTICAL THICKNESS (BONE); DEVELOPMENTAL STABILITY; DUAL ENERGY X RAY ABSORPTIOMETRY; FEMALE; FLUOROCHROME STAINING; FRACTURE FIXATION; HISTOLOGY; IMMUNOHISTOCHEMISTRY; IMPLANTATION; INJECTION; MICRO-COMPUTED TOMOGRAPHY; MICROPHOTOGRAPHY; NONHUMAN; OSSIFICATION; OSTEOPOROSIS; OVARIECTOMY; PROTEIN EXPRESSION; QUANTITATIVE ANALYSIS; RAT; SCANNING TRANSMISSION ELECTRON MICROSCOPY; SINGLE DRUG DOSE; TRABECULAR BONE; VASCULARIZATION; ADVERSE EFFECTS; ANIMAL; BIOSYNTHESIS; BLOOD VESSEL; DISEASE MODEL; DOSE RESPONSE; DRUG EFFECTS; FEMUR; GENE EXPRESSION REGULATION; GENETICS; HUMAN; INTRALESIONAL DRUG ADMINISTRATION; OSTEOPOROSIS, POSTMENOPAUSAL; PATHOPHYSIOLOGY; PHOTON ABSORPTIOMETRY; PRECLINICAL STUDY; SPRAGUE DAWLEY RAT; SURGERY; ULTRASTRUCTURE;

ABSORPTIOMETRY, PHOTON; ANIMALS; ANTIGENS, CD31; BLOOD VESSELS; BONE DENSITY; BONE MORPHOGENETIC PROTEIN 2; BONE SCREWS; DISEASE MODELS, ANIMAL; DOSE-RESPONSE RELATIONSHIP, DRUG; DRUG EVALUATION, PRECLINICAL; FEMALE; FEMUR; GENE EXPRESSION REGULATION; HUMANS; INJECTIONS, INTRALESIONAL; NEOVASCULARIZATION, PHYSIOLOGIC; OSSEOINTEGRATION; OSTEOGENESIS; OSTEOPOROSIS, POSTMENOPAUSAL; OVARIECTOMY; RATS; RATS, SPRAGUE-DAWLEY; SIMVASTATIN; VASCULAR ENDOTHELIAL GROWTH FACTOR A; VASCULAR ENDOTHELIAL GROWTH FACTOR RECEPTOR-2; VON WILLEBRAND FACTOR;

EID: 84929393273     PISSN: 12341010     EISSN: 16433750     Source Type: Journal    
DOI: 10.12659/MSM.892247     Document Type: Article

References (64)

1. Li Y, Feng G, Gao Y et al: Strontium ranelate treatment enhances hydroxyapatite- coated titanium screws fixation in osteoporotic rats. J Orthop Res, 2010; 28: 578–82
2. Ponnusamy KE, Iyer S, Gupta G, Khanna AJ: Instrumentation of the osteoporotic spine: biomechanical and clinical considerations. Spine J, 2011; 11: 54–63
3. Cherubino P, Ratti C, Fagetti A, Binda T: Total hip arthroplasty and bone fragility. Aging Clin Exp Res, 2011; 23: 76–77
4. Davignon J: Pleiotropic effects of pitavastatin. Br J Clin Pharmacol, 2012; 73: 518–35
5. Davignon J: Emphasis on pleiotropic effects, a new paradigm shift? Coron Artery Dis, 2004; 15: 223–25
6. Mundy G, Garrett R, Harris S et al: Stimulation of bone formation in vitro and in rodents by statins. Science, 1999; 286: 1946–49
7. Song C, Guo Z, Ma Q et al: Simvastatin induces osteoblastic differentiation and inhibits adipocytic differentiation in mouse bone marrow stromal cells. Biochem Biophys Res Commun, 2003; 308: 458–62
8. Chen PY, Sun JS, Tsuang YH et al: Simvastatin promotes osteoblast viability and differentiation via Ras/Smad/Erk/BMP-2 signaling pathway. Nutr Res, 2010; 30: 191–99
9. Li X, Song QS, Wang JY et al: Simvastatin induces estrogen receptor-alpha expression in bone, restores bone loss, and decreases ERalpha expression and uterine wet weight in ovariectomized rats. J Bone Miner Metab, 2011; 29: 396–403
10. Oka S, Matsumoto T, Kubo S et al: Local administration of low-dose simvastatin- conjugated gelatin hydrogel for tendon-bone healing in anterior cruciate ligament reconstruction. Tissue Eng Part A, 2013; 19: 1233–43
11. Tsartsalis AN, Dokos C, Kaiafa GD et al: Statins, bone formation and osteoporosis: hope or hype? Hormones (Athens), 2012; 11: 126–39
12. Patil S, Holt G, Raby N et al: Prospective, double blind, randomized, controlled trial of simvastatin in human fracture healing. J Orthop Res, 2009; 27: 281–85
13. Schachter M: Chemical, pharmacokinetic and pharmacodynamic properties of statins: an update. Fundam Clin Pharmacol, 2005; 19: 117–25
14. Lee Y, Schmid MJ, Marx DB et al: The effect of local simvastatin delivery strategies on mandibular bone formation in vivo. Biomaterials, 2008; 29: 1940–49
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. Fukui T, Ii M, Shoji T, Matsumoto T 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
17. Stadlinger B, Korn P, Todtmann N et al: Osseointegration of biochemically modified implants in an osteoporosis rodent model. Eur Cell Mater, 2013;25: 326–40; discussion 339–40
18. Pauly S, Luttosch F, Morawski M et al: Simvastatin locally applied from a biodegradable coating of osteosynthetic implants improves fracture healing comparable to BMP-2 application. Bone, 2009; 45: 505–11
19. Yueyi C, Xiaoguang H, Jingying W et al: Calvarial defect healing by recruitment of autogenous osteogenic stem cells using locally applied simvastatin. Biomaterials, 2013; 34: 9373–80
20. Yang N, Cui Y, Tan J et al: Local injection of a single dose of simvastatin augments osteoporotic bone mass in ovariectomized rats. J Bone Miner Metab, 2014; 32: 252–60
21. Gotz W, Reichert C, Canullo L et al: Coupling of osteogenesis and angiogenesis in bone substitute healing – a brief overview. Ann Anat, 2012; 194: 171–73
22. Zhao Q, Shen X, Zhang W et al: Mice with increased angiogenesis and osteogenesis due to conditional activation of HIF pathway in osteoblasts are protected from ovariectomy induced bone loss. Bone, 2012; 50: 763–70
23. Liu X, Tu Y, Zhang L et al: Prolyl hydroxylase inhibitors protect from the bone loss in ovariectomy rats by increasing bone vascularity. Cell Biochem Biophys, 2014; 69: 141–49
24. Cui X, Chopp M, Zacharek A et al: Chemokine, vascular and therapeutic effects of combination Simvastatin and BMSC treatment of stroke. Neurobiol Dis, 2009; 36: 35–41
25. Wang W, Lang JK, Suzuki G et al: Statins enhance clonal growth of late outgrowth endothelial progenitors and increase myocardial capillary density in the chronically ischemic heart. PLoS One, 2011; 6: e24868
26. Fang R, Jing H, Chai Z et al: Design and characterization of protein-quercetin bioactive nanoparticles. J Nanobiotechnology, 2011; 9: 19
27. Sun Z, Lee E, Herring SW: Cranial sutures and bones: growth and fusion in relation to masticatory strain. Anat Rec A Discov Mol Cell Evol Biol, 2004; 276: 150–61
28. Kajiwara H, Yamaza T, Yoshinari M et al: The bisphosphonate pamidronate on the surface of titanium stimulates bone formation around tibial implants in rats. Biomaterials, 2005; 26: 581–87
29. Nyangoga H, Mercier P, Libouban H et al: Three-dimensional characterization of the vascular bed in bone metastasis of the rat by microcomputed tomography (MicroCT). PLoS One, 2011; 6: e17336
30. Downey CM, Singla AK, Villemaire ML et al: Quantitative ex-vivo micro-computed tomographic imaging of blood vessels and necrotic regions within tumors. PLoS One, 2012; 7: e41685
31. Pastoureau P, Chomel A, Bonnet J: Specific evaluation of localized bone mass and bone loss in the rat using dual-energy X-ray absorptiometry subregional analysis. Osteoporos Int, 1995; 5: 143–49
32. Gabet Y, Kohavi D, Voide R et al: Endosseous implant anchorage is critically dependent on mechanostructural determinants of peri-implant bone trabeculae. J Bone Miner Res, 2010; 25: 575–83
33. Nyan M, Hao J, Miyahara T et al: Accelerated and Enhanced Bone Formation on Novel Simvastatin-Loaded Porous Titanium Oxide Surfaces. Clin Implant Dent Relat Res, 2014; 16(5): 675–83
34. Ruehe B, Heberer S, Bayreuther K, Nelson K: Effect of dehiscences to the bone response of implants with an Acid-etched surface: an experimental study in miniature pigs. J Oral Implantol, 2011; 37: 3–17
35. Ripamonti U, Klar RM, Renton LF, Ferretti C: Synergistic induction of bone formation by hOP-1, hTGF-beta3 and inhibition by zoledronate in macroporous coral-derived hydroxyapatites. Biomaterials, 2010; 31: 6400–10
36. Stadelmann VA, Gauthier O, Terrier A et al: Implants delivering bisphosphonate locally increase periprosthetic bone density in an osteoporotic sheep model. A pilot study. Eur Cell Mater, 2008; 16: 10–16
37. Peter B, Gauthier O, Laib S et al: Local delivery of bisphosphonate from coated orthopedic implants increases implants mechanical stability in osteoporotic rats. J Biomed Mater Res A, 2006; 76: 133–43
38. Moriyama Y, Ayukawa Y, Ogino Y et al: Local application of fluvastatin improves peri-implant bone quantity and mechanical properties: a rodent study. Acta Biomater, 2010; 6: 1610–18
39. Gao Y, Zou S, Liu X et al: The effect of surface immobilized bisphosphonates on the fixation of hydroxyapatite-coated titanium implants in ovariectomized rats. Biomaterials, 2009; 30: 1790–96
40. Wirth AJ, Goldhahn J, Flaig C et al: Implant stability is affected by local bone microstructural quality. Bone, 2011; 49: 473–78
41. Wirth AJ, Muller R, van Lenthe GH: Augmentation of peri-implant bone improves implant stability: quantification using simulated bone loss. J Orthop Res, 2012; 30: 178–84
42. Marco F, Milena F, Gianluca G, Vittoria O: Peri-implant osteogenesis in health and osteoporosis. Micron, 2005; 36: 630–44
43. Venesmaa PK, Kroger HP, Miettinen HJ et al: Monitoring of periprosthetic BMD after uncemented total hip arthroplasty with dual-energy X-ray absorptiometry – a 3-year follow-up study. J Bone Miner Res, 2001; 16: 1056–61
44. Wermelin K, Aspenberg P, Linderback P, Tengvall P: Bisphosphonate coating on titanium screws increases mechanical fixation in rat tibia after two weeks. J Biomed Mater Res A, 2008; 86: 220–27
45. Kim KH, Lee SH, Lee DY et al: Anterior bone cement augmentation in anterior lumbar interbody fusion and percutaneous pedicle screw fixation in patients with osteoporosis. J Neurosurg Spine, 2010; 12: 525–32
46. Sun P, Wang J, Zheng Y et al: BMP2/7 heterodimer is a stronger inducer of bone regeneration in peri-implant bone defects model than BMP2 or BMP7 homodimer. Dent Mater J, 2012; 31: 239–48
47. Feng X, McDonald JM: Disorders of bone remodeling. Annu Rev Pathol, 2011; 6: 121–45
48. Felix Lanao RP, Leeuwenburgh SC, Wolke JG, Jansen JA: In vitro degradation rate of apatitic calcium phosphate cement with incorporated PLGA microspheres. Acta Biomater, 2011; 7: 3459–68
49. Einhorn TA: Clinical applications of recombinant human BMPs: early experience and future development. J Bone Joint Surg Am, 2003; 85-A(Suppl.3): 82–88
50. Du Z, Chen J, Yan F, Xiao Y: Effects of Simvastatin on bone healing around titanium implants in osteoporotic rats. Clin Oral Implants Res, 2009; 20: 145–50
51. Nyan M, Sato D, Oda M et al: Bone formation with the combination of simvastatin and calcium sulfate in critical-sized rat calvarial defect. J Pharmacol Sci, 2007; 104: 384–86
52. Aro HT, Alm JJ, Moritz N et al: Low BMD affects initial stability and delays stem osseointegration in cementless total hip arthroplasty in women: a 2-year RSA study of 39 patients. Acta Orthop, 2012; 83: 107–14
53. Karrholm J, Borssen B, Lowenhielm G, Snorrason F: Does early micromotion of femoral stem prostheses matter? 4–7-year stereoradiographic follow- up of 84 cemented prostheses. J Bone Joint Surg Br, 1994; 76: 912–17
54. Linderback P, Agholme F, Wermelin K et al: Weak effect of strontium on early implant fixation in rat tibia. Bone, 2012; 50: 350–56
55. Jeong BC, Kim HJ, Bae IH et al: COMP-Ang1, a chimeric form of Angiopoietin 1, enhances BMP2-induced osteoblast differentiation and bone formation. Bone, 2010; 46: 479–86
56. Kanczler JM, Oreffo RO: Osteogenesis and angiogenesis: the potential for engineering bone. Eur Cell Mater, 2008; 15: 100–14
57. Bai Y, Yin G, Huang Z et al: Localized delivery of growth factors for angiogenesis and bone formation in tissue engineering. Int Immunopharmacol, 2013; 16: 214–23
58. Carano RA, Filvaroff EH: Angiogenesis and bone repair. Drug Discov Today, 2003; 8: 980–89
59. Brandi ML, Collin-Osdoby P: Vascular biology and the skeleton. J Bone Miner Res, 2006; 21: 183–92
60. Elzoghby AO, Samy WM, Elgindy NA: Albumin-based nanoparticles as potential controlled release drug delivery systems. J Control Release, 2012; 157: 168–82
61. Du C, Deng D, Shan L et al: A pH-sensitive doxorubicin prodrug based on folate-conjugated BSA for tumor-targeted drug delivery. Biomaterials, 2013; 34: 3087–97
62. Basarir K, Erdemli B, Can A et al: Osseointegration in arthroplasty: can simvastatin promote bone response to implants? Int Orthop, 2009; 33: 855–59
63. Ayukawa Y, Ogino Y, Moriyama Y et al: Simvastatin enhances bone formation around titanium implants in rat tibiae. J Oral Rehabil, 2010; 37: 123–30
64. Jansen JO, Lord JM, Thickett DR et al: Clinical review: Statins and trauma – a systematic review. Crit Care, 2013; 17: 227