Biomedical subjects

Fabian von Knoch

Publications and source records attributed to Fabian von Knoch.

8 recordsLinked to original sources

PubMed2006

Over-expression of p53/BAK in aseptic loosening after total hip replacement.

Particle-induced osteolysis is a major cause of aseptic loosening after total joint replacement. The possible induction of apoptosis has not been addressed in great detail. Thus far, it has been shown that ceramic and polyethylene particles can induce apoptosis of macrophages in vitro. The purpose of this study was to test the hypothesis that wears debris generated from total hip arthroplasty could induce cellular damage and apoptosis in vivo. We therefore determined by immunohistochemical methods if increased expression of p53, an important transcription factor, and BAK and Bcl-2, two important regulators of apoptosis, can be found in interface membranes and capsules of hips with aseptically loose implants. Strongly positive immunohistochemical staining for p53 and BAK was found in peri-implant tissues from patients with aseptic hip implant loosening. Differentiation of various cell types showed that macrophages stained positive for p53 in all capsule and interface specimens. p53 was frequently detected in giant cells. Positive staining of BAK in macrophages and giant cells was seen in all specimens. Some positive reactions were observed in fibroblasts, only two of 19 cases stained for p53 and three cases for BAK within synovial cells. Positive macrophages and giant cells were localized around polyethylene particles. While T-lymphocytes showed a regular BAK-staining, the other leukocytes were negative. Statistical analyses showed significant positive correlations (p < 0.001) between the presence of polyethylene and metal debris and the expression of BAK and p53. Polyethylene particles were surrounded by more positive macrophages and giant cells than were metal particles, indicating that polyethylene debris may be a stronger inductor of cell cycle arrest and apoptosis than metal debris. In this study apoptosis of macrophages, giant cells and T-lymphocytes in capsules and interface membranes of patients with aseptic hip implant loosening has been demonstrated in vivo. It is possible that the apoptotic cascade could evolve as a novel therapeutic target to prevent particle-induced osteolysis.

Adult↗

PubMed2006

[Pressfit of equatorially roughened cementless acetabular components--a finite element analysis].

AIM: Does the pressfit anchorage of cementless acetabular cups depend on the roughness of the pole? To answer this question the primary pressfit of two cementless acetabular cups which differ only with regard to the roughness of their poles were compared by means of finite elements analysis. MATERIALS AND METHODS: It was assumed that the material properties of bone are homogeneous, isotropic and linearly elastic. Material-specific values of cancellous bone with three different bone densities were used. Assumption of isotropy represents an approximation. RESULTS: Comparison of the two prosthesis designs revealed that both designs/shapes cause similar patterns of bone deformation and tension. CONCLUSIONS: It can therefore be concluded that with regard to pressfit anchorage the prosthesis with milled polar surface is according to FEA mechanically equivalent to the prosthesis with non-milled polar surface.

Acetabulum↗

PubMed2005

Suppression of polyethylene particle-induced osteolysis by exogenous osteoprotegerin.

Alterations of the key regulators of osteoclastogenesis, receptor activator of NF-kappaB (RANK), RANK ligand (RANKL), and osteoprotegerin (OPG) have been implicated in wear particle-induced osteolysis, the most common cause for implant failure in total joint replacements. This study investigated the effect of exogenous OPG on ultra-high-molecular-weight polyethylene (UHMWPE) particle-induced osteolysis. The murine calvarial osteolysis model was utilized in 28 C57BL/6J mice randomized to four groups. Group I underwent sham surgery only, group II received UHMWPE particles, and group III and IV particles and subcutaneous OPG starting from day 0 (group III) or day 5 (group IV) until sacrifice. After 2 weeks, calvaria were prepared for histology and histomorphometry. Bone resorption was measured within the midline suture using Giemsa staining and osteoclast numbers were determined using TRAP staining. UHMWPE particle implantation resulted in grossly pronounced osteoclastogenesis and bone resorption. Both immediate and delayed treatment with OPG counteracted these particle-induced effects significantly, suppressing osteoclast formation and bone resorption (p < 0.001 and p < 0.001, respectively). In conclusion, exogenous OPG markedly suppressed UHMWPE particle-induced osteolysis in a murine calvarial model. This important finding underscores the crucial significance of the OPG-RANKL-RANK signaling in wear particle-induced osteolysis. Exogenous OPG may prove an effective treatment modality for wear debris-mediated periprosthetic osteolysis after total joint arthroplasty.

Animals↗

PubMed2005

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

The most common cause of implant failure in joint replacement is aseptic loosening due to particle-induced osteolysis. Bisphosphonates have been shown to be effective against particle-induced osteolysis when administered daily. We investigated the effect of a single subcutaneous dose of a more potent third generation bisphosphonate on particle-induced osteolysis. We utilized the murine calvaria osteolysis model in C57BL/J6 mice. Bone resorption was measured as resorption within the midline suture using Giemsa staining. Twenty-eight mice were used, seven per group. Seven animals were treated with a single dose of zoledronic acid (ZA) directly after surgery and seven animals were treated four days postoperatively. For statistical analysis one-way ANOVA and a Student's t-test were used. Bone resorption was 0.26+/-0.09 mm(2) in animals with particle implantation, 0.14+/-0.05 mm(2) in animals with particle implantation and ZA treatment directly after surgery (p = 0.0047), and 0.15+/-0.05 mm(2) in animals with particle implantation and ZA treatment on the fourth postoperative day (p = 0.006). In conclusion, particle-induced bone resorption was markedly decreased by a single s.c. dose of a third generation bisphosphonate. This important new finding holds great promise, because single dose treatment of particle-induced osteolysis may reduce side effects compared to repeated application of bisphosphonates.

Animals↗

PubMed2005

Stimulation of bone formation by zoledronic acid in particle-induced osteolysis.

We investigated the effect of a single subcutaneous dose of zoledronic acid on particle-induced osteolysis and observed excessive regional new bone formation. We utilized the murine calvarial osteolysis model and polyethylene particles in C57BL/J6 mice. Twenty-eight mice were used, seven per group. Specimens were stained with Giemsa dye. The osteoid tissue area was determined. Bone thickness was measured as an indicator of bone growth. Net bone growth was significantly increased in animals with zoledronic acid treatment: 0.02 mm(2)+/-0.03 mm(2) in animals with particle implantation only (group 2), 0.25 mm(2)+/-0.08 mm(2) with particle implantation and zoledronic acid treatment directly after surgery (group 3; p=0.0018), and 0.21 mm(2)+/-0.11 mm(2) with particle implantation and zoledronic acid treatment on the fourth postoperative day (group 4; p=0.0042). The mean bone thickness was 0.2 mm+/-0.04 mm (range 0.17 mm-0.31 mm) in group 1 (sham controls) and 0.16 mm+/-0.02 mm (range 0.14 mm-0.19 mm) in group 2, 0.31 mm+/-0.04 mm (range 0.28 mm-0.39 mm) in group 3, and 0.29 mm+/-0.02 mm (range 0.28 mm-0.34 mm) in group 4. Student's t-test revealed a statistically significant difference between groups 2 and 3 (p=0.00042), and groups 2 and 4 (p=0.0019). In conclusion, our observational study suggests that zoledronic acid may stimulate bone apposition locally in the process of particle-induced osteolysis.

Animals↗

PubMed2005

The effect of simvastatin on polyethylene particle-induced osteolysis.

This study aimed to investigate the effects of the HMG-CoA reductase inhibitor simvastatin on ultra-high molecular weight polyethylene (UHMWPE) particle-induced osteolysis. The murine calvarial osteolysis model was used 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 two weeks, calvaria were processed for histomorphometry. Bone resorption was measured as resorption within the midline suture using Giemsa staining. Osteoclast numbers were determined per high-power field using TRAP-staining. Statistical analysis was performed using one-way ANOVA and Student's t-test. Bone resorption in midline suture was 0.094+/-0.007 mm(2) in sham controls (group I), 0.25+/-0.025 mm(2) after particle implantation without further intervention (group II), and 0.131+/-0.02 mm(2) with particle implantation and additional simvastatin treatment (group III) (p=0.00003). Osteoclast numbers were 15.3+/-3.6 in group I, 48.7+/-7.1 in group II and 6.2+/-3.1 in group III (p=0.00002). In conclusion, simvastatin treatment markedly decreased UHMWPE particle-induced osteolysis in a murine calvarial model. This finding suggests that simvastatin may have a role for noninvasive prevention and treatment of wear debris-mediated periprosthetic osteolysis after total joint arthroplasty.

Animals↗

PubMed2005

Promotion of bone formation by simvastatin in polyethylene particle-induced osteolysis.

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.

Animals↗

PubMed2005

Effects of bisphosphonates on proliferation and osteoblast differentiation of human bone marrow stromal cells.

Bisphosphonates are well known potent inhibitors of osteoclast activity and are widely used to treat metabolic bone diseases. Recent evidence from in vitro and in vivo studies indicates that bisphosphonates may additionally promote osteoblastic bone formation. In this study, we evaluated the effects of three FDA-approved and clinically utilized bisphosphonates, on the proliferation and osteogenic differentiation of human bone marrow stromal cells (BMSC). BMSC were obtained from patients undergoing primary total hip arthroplasty for end-stage degenerative joint disease. Cells were treated with or without a bisphosphonate (alendronate, risedronate, or zoledronate) and analyzed over 21 days of culture. Cell proliferation was determined by direct cell counting. Osteogenic differentiation of BMSC was assessed with alkaline phosphatase bioassay and gene expression analyses using conventional RT-PCR as well as real-time quantitative RT-PCR. All bisphosphonates tested enhanced the proliferation of BMSC after 7 and 14 days of culture. Steady-state mRNA levels of key genes involved in osteogenic differentiation such as bone morphogenetic protein-2 (BMP-2), bone sialoprotein-II, core-binding factor alpha subunit 1 (cbfa1) and type 1 collagen, were generally increased by bisphosphonate treatment in a type- and time-dependent manner. Gene expression levels varied among the different donors. Enhancement of osteogenic differentiation was most pronounced after 14 days of culture, particularly following zoledronate treatment (p < 0.05 for BMP-2). In conclusion, using a clinically relevant in vitro model we have demonstrated that bisphosphonates enhance proliferation of BMSC and initiate osteoblastic differentiation. When administered around joint replacements, bisphosphonates may potentially compensate for the deleterious effects of particulate wear debris at the bone-implant interface, by encouraging increased numbers of cells committed to the osteoblastic phenotype, and thus improve the longevity of joint replacements.

Bone Marrow Cells↗