Biochemical markers of particle induced osteolysis in C57BL/6 mice

Kauther, Max Daniel; Zimmermann, Christina; Bachmann, Hagen S.; Broecker-Preuß, Martina; Hilken, Gero; Knoch, Marius von; Wedemeyer, Christian

doi:10.1515/cclm.2010.305

Cited by 4 publications

(4 citation statements)

References 32 publications

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“…Unfortunately, the extent of postoperative osteolysis did not correlate with any of the analyzed serum parameters. We recently described DPD as a possible marker to detect particle-induced osteolysis [ 30 ], yet despite this finding, it could not be correlated with the extent of osteolysis in Calca -/- mice in this study, although the largest extent of osteolysis was found in these groups. Further biochemical markers should be analyzed for detection of particle-induced osteolysis.…”

Section: Discussioncontrasting

confidence: 74%

Calcitonin substitution in calcitonin deficiency reduces particle-induced osteolysis

Kauther

Bachmann

Neuerburg

et al. 2011

BMC Musculoskelet Disord

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BackgroundPeriprosthetic osteolysis is a major cause of aseptic loosening in joint arthroplasty. This study investigates the impact of CT (calcitonin) deficiency and CT substitution under in-vivo circumstances on particle-induced osteolysis in Calca -/- mice.MethodsWe used the murine calvarial osteolysis model based on ultra-high molecular weight polyethylene (UHMWPE) particles in 10 C57BL/6J wild-type (WT) mice and twenty Calca -/- mice. The mice were divided into six groups: WT without UHMWPE particles (Group 1), WT with UHMWPE particles (Group 2), Calca -/- mice without UHMWPE particles (Group 3), Calca -/- mice with UHMWPE particles (Group 4), Calca -/- mice without UHMWPE particles and calcitonin substitution (Group 5), and Calca -/- mice with UHMWPE particle implantation and calcitonin substitution (Group 6). Analytes were extracted from serum and urine. Bone resorption was measured by bone histomorphometry. The number of osteoclasts was determined by counting the tartrate-resistant acid phosphatase (TRACP) + cells.ResultsBone resorption was significantly increased in Calca -/- mice compared with their corresponding WT. The eroded surface in Calca -/- mice with particle implantation was reduced by 20.6% after CT substitution. Osteoclast numbers were significantly increased in Calca -/- mice after particle implantation. Serum OPG (osteoprotegerin) increased significantly after CT substitution.ConclusionsAs anticipated, Calca -/- mice show extensive osteolysis compared with wild-type mice, and CT substitution reduces particle-induced osteolysis.

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Section: Discussioncontrasting

confidence: 74%

Calcitonin substitution in calcitonin deficiency reduces particle-induced osteolysis

Kauther

Bachmann

Neuerburg

et al. 2011

BMC Musculoskelet Disord

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“…The effects of wear particles on bone are commonly investigated using small rodent models ( von Knoch et al, 2004b ; Wedemeyer et al, 2007 ; Nich et al, 2010 ; Kauther et al, 2010 ; Jin et al, 2011 ; Takahashi et al, 2011 ; von Knoch et al, 2005a ; Darowish et al, 2009 ; Childs et al, 2001 ; von Knoch et al, 2005b ; Ren et al, 2006 ). In mice, placement of particles over the calvarium induces osteolysis that is readily detectable using histology ( von Knoch et al, 2004a ; von Knoch et al, 2004b ; Wedemeyer et al, 2007 ; Nich et al, 2010 ; Jin et al, 2011 ; Takahashi et al, 2011 ; von Knoch et al, 2005a ; Darowish et al, 2009 ; Childs et al, 2001 ; von Knoch et al, 2005b ; Ren et al, 2006 ; Yang et al, 2004 ; K. Ren et al, 2011 ) or micro-computed tomography (μCT) ( Wedemeyer et al, 2007 ; Nich et al, 2010 ; Kauther et al, 2010 ; Darowish et al, 2009 ; Ren et al, 2006 ; K. Ren et al, 2011 ; Burton et al, 2013 ; Green et al, 2013 ). Animal studies to date have appropriately focused on the role of focal bone loss contributing to implant loosening.…”

Section: Introductionmentioning

confidence: 99%

Polyethylene particles inserted over calvarium induce cancellous bone loss in femur in female mice

et al. 2018

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Focal bone resorption (osteolysis) induced by wear particles contributes to long-term orthopedic joint failure. However, the impact of focal osteolysis on remote skeletal sites has received less attention. The goal of this study was to determine the effects of polyethylene particles placed over calvaria on representative axial and appendicular skeletal sites in female mice. Because recent work has identified housing temperature as an important biological variable in mice, response to particle treatment was measured in animals housed at room (22 °C) and thermoneutral (32 °C) temperature. Osteolysis was evident in skeletal tissue adjacent to particle insertion. In addition, cancellous bone loss was observed in distal femur metaphysis. The bone loss was associated with lower osteoblast-lined perimeter and lower mineralizing perimeter in distal femur, lower osteocalcin gene expression in tibia, and lower serum osteocalcin, suggesting the response was due, at least in part, to reduced bone formation. Mild cold stress induced by sub-thermoneutral housing resulted in cancellous bone loss in distal femur and lumbar vertebra but did not influence skeletal response to particles. In summary, the results indicate that focal inflammation induced by polyethylene particles has the potential to result in systemic bone loss. This is significant because bone loss is a risk factor for fracture.

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“…11 Considerable biomarker research has been performed in animal models of osteoporosis, leading to improved understanding of pathogenesis and how the skeleton responds to pharmaceuticals. 12 Only three osteolysis-related animal models have thus far reported circulating biomarker concentration changes, [13][14][15] and none have determined the relative contributions of local and remote bone remodeling, even though it is well known that local skeletal insult can lead to elevated bone remodeling at remote sites. 16,17 Our lab recently developed a rat model of particleinduced peri-implant osteolysis to study the pathophysiology of implant loosening.…”

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confidence: 99%

Particle‐induced osteolysis is not accompanied by systemic remodeling but is reflected by systemic bone biomarkers

Ross

Virdi

Liu

et al. 2014

Journal Orthopaedic Research

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Particle-induced osteolysis is caused by an imbalance in bone resorption and formation, often leading to loss of implant fixation. Bone remodeling biomarkers may be useful for identification of osteolysis and studying pathogenesis, but interpretation of biomarker data could be confounded if local osteolysis engenders systemic bone remodeling. Our goal was to determine if remote bone remodeling contributes to biomarker levels. Serum concentrations of eight biomarkers and bone remodeling rates at local (femur), contiguous (tibia), and remote (humerus and lumbar vertebra) sites were evaluated in a rat model of particle-induced osteolysis. Serum CTX-1, cathepsin K, PINP, and OPG were elevated and osteocalcin was suppressed in the osteolytic group, but RANKL, TRAP 5b, and sclerostin were not affected at the termination of the study at 12 weeks. The one marker tested longitudinally (CTX-1) was elevated by 3 weeks. We found increased bone resorption and decreased bone formation locally, subtle differences in contiguous sites, but no differences remotely at 12 weeks. Thus, the skeletal response to local particle challenge was not systemic, implying that the observed differences in serum biomarker levels reflect differences in local remodeling. ß

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Biochemical markers of particle induced osteolysis in C57BL/6 mice

Abstract: DPD can be regarded as a valuable parameter for detecting UHMWPE induced osteolysis in the calvarian model. Further studies of serum parameters should focus on the clinical relevance in aseptic prosthetic loosening.

Cited by 4 publications

References 32 publications

Calcitonin substitution in calcitonin deficiency reduces particle-induced osteolysis

Calcitonin substitution in calcitonin deficiency reduces particle-induced osteolysis

Polyethylene particles inserted over calvarium induce cancellous bone loss in femur in female mice

Particle‐induced osteolysis is not accompanied by systemic remodeling but is reflected by systemic bone biomarkers

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