title: [A comparison of the antiresorptive effects of bisphosphonates and statins on polyethylene particle-induced osteolysis].
abstract: An ongoing unraveling of the molecular mechanisms in aseptic loosening of hip arthroplasty has opened up novel potential pharmacological interventions. In this study the antiresorptive effects of the bisphosphonate zoledronate and the statin simvastatin on ultra high molecular weighted polyethylene (UHMWPE) particle-induced osteolysis were compared. Two previous studies of our group based on the murine calvarial model of UHWMPE particle-induced osteolysis were pooled to form four study groups. Animals in group I (n=14) underwent sham surgery only. In groups II (n=14), III (n=7) and IV (n=7) UHMWPE particles were implanted on the calvariae. Animals in groups III and IV were additionally treated with zoledronate (single 25 microg/kg s.c. injection) and simvastatin (120 mg/day p.o. for 14 days), respectively. After two weeks, calvaria were processed for undecalcified histomorphometry. Bone resorption was measured using Giemsa staining. Osteoclast numbers were determined using TRAP-staining. UHMWPE particle implantation resulted in a grossly pronounced osteolytic activity with significantly increased values of bone resorption (p < 0.001) and osteoclast numbers (p < 0.001). Additional treatment with zoledronate or simvastatin counteracted the particle-induced effects. A comparison of the two medical treatments revealed no statistically significant differences in bone resorption (p = 0.63) and osteoclast numbers (p = 0.41). A single dose of the bisphosphonate zoledronate decreased UHMWPE particle-induced osteolysis in a murine calvarial model as effectively as a daily treatment with simvastin. Both drug groups may have a preventive and therapeutic role as antiresorptive agents in wear particle-induced bone resorption following total joint replacement.
authors: Untersuchung durchgeführt an der Klinik und Poliklinik für Orthopädie der Universität Duisburg-Essen. fabianvonknoch@yahoo.com
authors: F
authors: F
authors: von Knoch
authors: C
authors: C
authors: Wedemeyer
authors: A
authors: A
authors: Heckelei
authors: C
authors: C
authors: Sprecher
authors: G
authors: G
authors: Saxler
authors: G
authors: G
authors: Hilken
authors: F
authors: F
authors: Henschke
authors: M
authors: M
authors: von Knoch
authors: H
authors: H
authors: Bereiter
authors: F
authors: F
authors: Löer
authors: M
authors: M
authors: von Knoch
mesh_terms: D000818:Animals; D001862:Bone Resorption / Q000209:etiology / Q000473:pathology* / Q000517:prevention & control*; D004164:Diphosphonates / Q000627:therapeutic use*; D005260:Female; D005549:Foreign-Body Reaction / Q000209:etiology / Q000473:pathology / Q000517:prevention & control; D007093:Imidazoles / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010014:Osteolysis / Q000209:etiology / Q000473:pathology* / Q000517:prevention & control*; D010316:Particle Size; D011095:Polyethylenes / Q000009:adverse effects*; D019821:Simvastatin / Q000627:therapeutic use*; D012886:Skull / Q000187:drug effects / Q000473:pathology; D016896:Treatment Outcome; D000077211:Zoledronic Acid
chemical_list: D004164:Diphosphonates; D007093:Imidazoles; D011095:Polyethylenes; C111601:ultra-high molecular weight polyethylene; D000077211:Zoledronic Acid; D019821:Simvastatin