title: Promotion of bone formation by simvastatin in polyethylene particle-induced osteolysis.
abstract: The effects of statins on bone formation in periprosthetic osteolysis have not been determined to date. We investigated the effect of the HMG-CoA reductase inhibitor simvastatin on osteoblastic bone formation under conditions of ultra-high molecular weight polyethylene (UHMWPE) particle-induced osteolysis. The murine calvarial osteolysis model was utilized in 21 C57BL/J6 mice randomized to three groups. Group I underwent sham surgery only, group II received UHMWPE particles, and group III, particles and simvastatin treatment. After 2 weeks, calvaria were processed for histomorphometry and stained with Giemsa dye. New bone formation was measured as osteoid tissue area within the midline suture. Bone thickness was quantified as indicator of net bone growth. Statistical analysis was performed using one-way ANOVA and a Student's t-test. New bone formation and bone thickness were significantly enhanced following simvastatin treatment. New bone formation was 0.008+/-0.008 mm2 in sham controls (group I), 0.015+/-0.012 mm2 after particle implantation without further intervention (group II), compared to 0.083+/-0.021 mm2 with particle implantation and simvastatin treatment (group III) (p=0.003). The bone thickness was 0.213+/-0.007 mm in group I, 0.183+/-0.005 mm in group II, and 0.238+/-0.009 mm in group III (p=0.00008). In conclusion, simvastatin treatment markedly promoted bone formation and net bone growth in UHMWPE particle-induced osteolysis in a murine calvarial model. These new findings indicate that simvastatin may have favorable osteoanabolic effects on wear debris-mediated osteolysis after total joint arthroplasty, involving local stimulation of osteoblastic bone formation.
authors.affiliation: Department of Orthopaedic Surgery, Kantonsspital Chur, Loestrasse 170, 7000 Chur, Switzerland. fabianvonknoch@yahoo.com
authors.forename: Fabian
authors.initials: F
authors.lastname: von Knoch
authors.forename: Christian
authors.initials: C
authors.lastname: Wedemeyer
authors.forename: Anja
authors.initials: A
authors.lastname: Heckelei
authors.forename: Guido
authors.initials: G
authors.lastname: Saxler
authors.forename: Gero
authors.initials: G
authors.lastname: Hilken
authors.forename: Jochen
authors.initials: J
authors.lastname: Brankamp
authors.forename: Thomas
authors.initials: T
authors.lastname: Sterner
authors.forename: Stefan
authors.initials: S
authors.lastname: Landgraeber
authors.forename: Frank
authors.initials: F
authors.lastname: Henschke
authors.forename: Franz
authors.initials: F
authors.lastname: Löer
authors.forename: Marius
authors.initials: M
authors.lastname: von Knoch
mesh_terms: D000818:Animals; D001399:Azure Stains / Q000494:pharmacology; D018786:Bone Substitutes / Q000737:chemistry*; D001842:Bone and Bones / Q000187:drug effects; D005260:Female; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology; D008297:Male; D008422:Materials Testing; D051379:Mice; D008810:Mice, Inbred C57BL; D008855:Microscopy, Electron, Scanning; D010012:Osteogenesis; D010014:Osteolysis; D020959:Polyethylene / Q000737:chemistry*; D011095:Polyethylenes; D011475:Prosthesis Failure; D019821:Simvastatin / Q000737:chemistry* / Q000494:pharmacology; D013314:Stress, Mechanical
chemical_list: D001399:Azure Stains; D018786:Bone Substitutes; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011095:Polyethylenes; C111601:ultra-high molecular weight polyethylene; D020959:Polyethylene; D019821:Simvastatin