The decrease of particle-induced osteolysis after a single dose of bisphosphonate

Knoch, Marius von; Wedemeyer, Christian; Pingsmann, A.; Knoch, Fabian von; Hilken, Gero; Sprecher, Christoph M.; Henschke, F.; Barden, B.; Löer, F.

doi:10.1016/j.biomaterials.2004.06.010

Cited by 54 publications

(40 citation statements)

References 17 publications

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“…Staining of the osteoclasts was partial and mild to moderate in both groups but the number of osteoclasts differed. There were 45.14 osteoclasts (range, in the Group II animals and 11.86 (range, [6][7][8][9][10][11][12][13][14][15][16][17][18] in the animals of Group IV, in the sham controls we counted 3.86 (range, 2-7) in Group I and 3.57 (range, 2-6) in Group III (Fig. 4).…”

Section: Histology and Immunohistochemistrymentioning

confidence: 92%

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Pan-caspase inhibition suppresses polyethylene particle-induced osteolysis

et al. 2009

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Particle-induced osteolysis is a major cause of aseptic loosening after total joint replacement. Earlier studies demonstrated apoptotic macrophages, giant cells, fibroblasts and T-lymphocytes in capsules and interface membranes of patients with aseptic hip implant loosening. The aim of the current study was to determine in a murine calvarial model of wear particle-induced osteolysis whether inhibition of apoptosis using the pan-caspase inhibitor BOC-D-FMK reduces aseptic loosening. Healthy 12-week-old male C57BL/6J mice were treated with UHMWPE particles and received a daily peritoneal injection of BOK-D-FMK, respectively only buffer at a dose of 3 mg/kg of body weight for 12 days until sacrifice. Bone resorption was measured by histomorphometry, micro CT (computed tomography) and TRAP-5b serum analysis. Apoptosis was measured using caspase-3 cleaved staining. The results demonstrated that UHMWPE particles induced stronger apoptotic reactions in macrophages and osteoblasts and increased bone resorption in non-specifically treated mice, whereas peritoneal application of BOC-D-FMK significantly counteracted these adverse particle-related effects. We think that in particle-induced osteolysis apoptosis is pathologically increased, and that failure to reduce the quantity of apoptotic bodies leads to an up-regulation of proinflammatory cytokines, which may be responsible for the induction of osteolysis. We showed for the first time in vivo that a reduction in apoptosis leads to a significant reduction in particle-induced osteolysis. Clinically, the apoptotic cascade could become an interesting novel therapeutic target to modulate particle-induced osteolysis.

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Section: Histology and Immunohistochemistrymentioning

confidence: 92%

“…More than 34% of the particles were smaller than 1 lm, with a mean particle size (given as equivalent circle diameter) of 1.74 ± 1.43 lm (range 0.05-11.6). A detailed morphological particle description has been recently published by our group [14].…”

Section: Particlesmentioning

confidence: 99%

Pan-caspase inhibition suppresses polyethylene particle-induced osteolysis

et al. 2009

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“…Various in vitro and animal studies have shown encouraging results (Horowitz et al, 1996, Millett et al, 2002, Shanbhag et al, 1997, von Knoch et al, 2005. However currently, convincing results from clinical studies supporting the use of bisphosphonates are still lacking.…”

Section: Future Perspectivesmentioning

confidence: 96%

Evidence Linking Elevated Oxidative Stress and Aseptic Loosening of Hip Arthroplasty

Kinov¹,

Tivchev²

2012

Recent Advances in Arthroplasty

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“…Oral alendronate treatment protected the dogs from osteoclast mediated bone loss and thus implant loosening (Shanbhag et al, 1997). Further experimental studies have confirmed these finding of inhibited particle induced bone resorption in bisphosphonates treated animals (Millett et al, 2002, von Knoch et al, 2005b, Wedemeyer et al, 2005. However, in all studies wear particles were introduced intraoperatively and treatment with bisphosphonates was initiated directly after surgery.…”

Section: Study III (Bisphosphonate Study)mentioning

confidence: 96%

“…This particle induced periprosthetic osteolysis was inhibited by bisphosphonates in experimental studies in dogs (Shanbhag et al, 1997, Millett et al, 2002, von Knoch et al, 2005b, Wedemeyer et al, 2005. However, in a clinical setting of patients with demonstrated aseptic loosening who were awaiting revision surgery, six months treatment with bisphosphonates did not alter the need for revision surgery (Lyons et al, 2009).…”

Section: Study Iii: Bisphosphonatesmentioning

confidence: 99%