Christian Wedemeyer

Particle-Induced Osteolysis in Three-Dimensional Micro-Computed Tomography

Small-animal models are useful for the in vivo study of particle-induced osteolysis, the most frequent cause of aseptic loosening after total joint replacement. Microstructural changes associated with particle-induced osteolysis have been extensively explored using two-dimensional (2D) techniques. However, relatively little is known regarding the 3D dynamic microstructure of particle-induced osteolysis. Therefore, we tested micro-computed tomography (micro-CT) as a novel tool for 3D analysis of wear debris-mediated osteolysis in a small-animal model of particle-induced osteolysis. The murine calvarial model based on polyethylene particles was utilized in 14 C57BL/J6 mice randomly divided into two groups. Group 1 received sham surgery, and group 2 was treated with polyethylene particles. We performed 3D micro-CT analysis and histological assessment. Various bone morphometric parameters were assessed. Regression was used to examine the relation between the results achieved by the two methods. Micro-CT analysis provides a fully automated means to quantify bone destruction in a mouse model of particle-induced osteolysis. This method revealed that the osteolytic lesions in calvaria in the experimental group were affected irregularly compared to the rather even distribution of osteolysis in the control group. This is an observation which would have been missed if histomorphometric analysis only had been performed, leading to false assessment of the actual situation. These irregularities seen by micro-CT analysis provide new insight into individual bone changes which might otherwise be overlooked by histological analysis and can be used as baseline information on which future studies can be designed.

Digital templating in total hip arthroplasty with the Mayo stem

PatientsIn 40 patients undergoing total hip arthroplasty with the Mayo femoral stem we studied how preoperative digital templating corresponded to the actual intraoperative choice of implant size, position, offset and restoration of leg length.ResultsThe preoperatively planned sizes of the components showed a high rate of coincidence with the sizes used intraoperatively [Intraclass Correlation Coefficient (ICC) 0.661–0.810]. However, the agreements in offset and CCD correction were poor (ICC 0.476, 0.253). This could be statistically attributed to the change in the distance from the medial margin of the stem to the medial margin of the medial femoral cortex and the height of osteotomy. The agreement in leg length correction was moderate (ICC 0.583), which was attributed to the change in the hip rotation center and the height of osteotomy.ConclusionCareful preoperative planning was useful for accurate size choice of the Mayo prosthesis. Factors such as the height of osteotomy and the distance from the medial margin of the stem to the medial margin of the medial femoral cortex in relation to the position of the Mayo stem should be taken into account in order to restore ideal offset and leg length.

Polyethylene Particle–Induced Bone Resorption in α-Calcitonin Gene–Related Peptide–Deficient Mice†

This study investigates the impact of α‐CGRP on bone metabolism after implantation of polyethylene particles. α‐CGRP knockout mice showed less osteolysis compared with wildtype mice. The local neurogenic microenvironment might be a crucial factor in particle‐induced osteolysis.

Breakdance injuries and overuse syndromes in amateurs and professionals.

Background Serious injuries due to breakdancing have been presented only as singular case reports to date. So far, there have been no comprehensive studies about injuries in this sport. Hypothesis Professional breakdancing might lead to a higher incidence of injuries than amateur training. Wearing safety equipment is correlated with a decreased incidence of injuries and pain. Study Design Descriptive epidemiology study. Methods The retrospective study surveyed 40 breakdance professionals and 104 amateurs by questionnaire. Results There were 1665 injuries and 206 overuse syndromes found in 380 588 hours of training, leading to a loss of 10 970.6 training days. Professionals reported significantly (P < .001) more injuries and overuse syndromes with significantly more injuries of the wrist (P < .001), knee (P < .001), hip/thigh (P = .003), ankle/foot (P = .013), and elbow (P = .033). No significant differences were found in the time lost per injury and the time lost per overuse syndrome. Pain occurred most frequently in the region of the wrist, spine, shoulder, and ankle. A negative correlation between protective gear and injuries or frequency of pain could not be shown. Conclusion Breakdancing must be considered as a potentially high-risk dancing sport. Even with severe injuries, dancers interrupt training only for limited periods of time. Clinical Relevance Breakdance injuries and overuse should not be underestimated. Physicians should be aware of the common risks in this highly acrobatic kind of dancing.

Alumina ceramic particles, in comparison with titanium particles, hardly affect the expression of RANK‐, TNF‐α‐, and OPG‐mRNA in the THP‐1 human monocytic cell line

Particle-induced osteolysis is the most frequent cause of aseptic loosening after total joint replacement. We performed a study to illuminate the effect of ceramic particles with different diameters and concentrations on the mRNA expression of certain key regulators in particle-induced aseptic osteolysis (RANK, RANKL, OPG, and TNF-alpha) in THP-1 macrophage-like cells. Titanium particles were used as a positive control. RNA was analyzed by quantitative RTPCR. Our results demonstrate that alumina ceramic particles, regardless of particle size, caused only slight upregulations of RANK, TNF-alpha, and OPG mRNA, whose levels were significantly lower in comparison with those of titanium particles (p < 0.05). The continuous increasing tendency to time and particle-dependent mRNA expression of all the parameters stimulated by titanium particles was not found after stimulation with ceramic materials. Even after the concentration of ceramic particles was increased, only a mild upregulation of mRNA expression was found. Furthermore, we observed that the bioinert properties of ceramic particles did not change much in diameters ranging from 0.5 to 1.5 microm. At most of the measuring time points, there was no significant difference between the reactions of the large and small particles in this range. Our results support the theory about the relative bioinert properties of alumina ceramic particles.

RANKL-associated suppression of particle-induced osteolysis in an aged model of Calcitonin and α-CGRP deficiency.

An aging population with higher bone turnover intensifies the need for joint replacement surgery. However, particle-induced osteolysis (PIO) remains a major cause of early implant loosening. Differences in bone remodeling between young and aged Calcitonin (CT)- and α-CGRP (Calcitonin gene-related peptide)-deficient mice (Calca(-/-)) might modify our previous findings regarding CT/α-CGRP in PIO. This may have important implications for PIO in an aging population. Four groups of twelve-month-old wild-type and Calca(-/-) mice underwent either SHAM surgery with and without CT, or polyethylene-particle implantation with related treatment. Morphometric changes were detected using μ-CT, histomorphometric analysis and by counting TRAP(+) cells (osteoclast-staining). Bone remodeling was assessed using serum and urinary markers. There was no osteolysis in aged particle-treated Calca(-/-) animals and the effect of CT on PIO was reduced compared to wild-type mice. However, there were significantly higher numbers of TRAP(+) cells in Calca(-/-) animals, and bone remodeling markers revealed a significant increase in OPG/OCN and a significant reduction in RANKL compared to aged wild-type mice. CT/α-CGRP modulates bone cell activity in PIO in aged mice in a way that is distinct from young animals. This may have implications for the treatment of PIO in the periprosthetic surface of joint replacements in an aging population.

Effects of alpha-calcitonin gene-related peptide on osteoprotegerin and receptor activator of nuclear factor-κB ligand expression in MG-63 osteoblast-like cells exposed to polyethylene particles

BackgroundRecent studies demonstrated an impact of the nervous system on particle-induced osteolysis, the major cause of aseptic loosening of joint replacements.MethodsIn this study of MG-63 osteoblast-like cells we analyzed the influence of ultra-high molecular weight polyethylene (UHMWPE) particles and the neurotransmitter alpha-calcitonin gene-related peptide (CGRP) on the osteoprotegerin/receptor activator of nuclear factor-κB ligand/receptor activator of nuclear factorκB (OPG/RANKL/RANK) system. MG-63 cells were stimulated by different UHMWPE particle concentrations (1:100, 1:500) and different doses of alpha-CGRP (10-7 M, 10-9 M, 10-11 M). RANKL and OPG mRNA expression and protein levels were measured by RT-PCR and Western blot.ResultsIncreasing particle concentrations caused an up-regulation of RANKL after 72 hours. Alpha-CGRP showed a dose-independent depressive effect on particle-induced expression of RANKL mRNA in both cell-particle ratios. RANKL gene transcripts were significantly (P < 0.05) decreased by alpha-CGRP treatment after 48 and 72 hours. OPG mRNA was significantly down-regulated in a cell-particle ratio of 1:500 after 72 hours. Alpha-CGRP concentrations of 10-7 M lead to an up-regulation of OPG protein.ConclusionIn conclusion, a possible osteoprotective influence of the neurotransmitter alpha-CGRP on particle stimulated osteoblast-like cells could be shown. Alpha-CGRP might be important for bone metabolism under conditions of particle-induced osteolysis.

Calcitonin substitution in calcitonin deficiency reduces particle-induced osteolysis

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.

Hemipelvectomy- only a salvage therapy?

After the first hemipelvectomy in 1891 significant advances have been made in the fields of preoperative diagnosis, surgical technique and adjuvant treatment in patients with pelvic tumors. The challenging surgical removal of these rare malignant bone or soft tissue tumors accompanied by interdisciplinary therapy is mostly the only chance of cure, but bares the risk of intensive bleeding and infection. The reconstruction after hemipelvectomy is of importance for the later outcome and quality of life for the patient. Here, plastic surgery with microvascular free flaps or local rotational flaps improved the reconstruction and reduced infection rates. Average local recurrence rates of 14% demonstrate good surgical results, but 5 year survival rates of only 50% are described for some tumor entities, showing the importance of a multimodal collaboration. On a basis of a selective literature review the history, indications, treatment options and outcome of hemipelvectomies are presented.

BCL2-938C > A and CALCA-1786T > C polymorphisms in aseptic loosened total hip arthroplasty

The search for influencing factors and new pathways in aseptic loosening of arthroplasties is a major focus of recent studies. Analyses of polymorphisms of genes revealed a correlation between a specific allele variant and aseptic loosening. The BCL2 gene encoding Bcl-2 with its BCL2 -938C > A polymorphism is a crucial factor of cell cycle control and cell survival. The CALCA -1786T > C polymorphism belongs to the CALCA gene encoding alpha-Calcitonin Gene Related Peptide (CGRP) and Calcitonin. Both proteins are important in bone metabolism and capable to influence the process of aseptic loosening. To date, no studies are reported for aseptic loosening with these two single nucleotide polymorphisms (SNPs). In a retrospective study we determined the distribution of the BCL2-938C > A and the CALCA-1786T > C polymorphisms in 87 subjects with aseptic loosened hip arthroplasties using RFLP and pyrosequencing analysis. Genotype distribution with prognosis of the hip arthroplasty showed neither an association with clinical characteristics of the patients nor the implantation technique. We were unable to detect any influence of these polymorphisms on time to aseptic loosening.