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Item type:Publication, Access status: with files , Osteoidosis leads to altered differentiation and function of osteoclasts(Wiley-Blackwell, 2020-04-13); ; ; ; In patients with osteomalacia, a defect in bone mineralization leads to changed characteristics of the bone surface. Considering that the properties of the surrounding matrix influence function and differentiation of cells, we aimed to investigate the effect of osteoidosis on differentiation and function of osteoclasts. Based on osteomalacic bone biopsies, a model for osteoidosis in vitro (OIV) was established. Peripheral blood mononuclear cells were differentiated to osteoclasts on mineralized surfaces (MS) as internal control and on OIV. We observed a significantly reduced number of osteoclasts and surface resorption on OIV. Atomic force microscopy revealed a significant effect of the altered degree of mineralization on surface mechanics and an unmasking of collagen fibres on the surface. Indeed, coating of MS with RGD peptides mimicked the resorption phenotype observed in OIV, suggesting that the altered differentiation of osteoclasts on OIV might be associated with an interaction of the cells with amino acid sequences of unmasked extracellular matrix proteins containing RGD sequences. Transcriptome analysis uncovered a strong significant up-regulation of transmembrane glycoprotein TROP2 in osteoclastic cultures on OIV. TROP2 expression on OIV was also confirmed on the protein level and found on the bone surface of patients with osteomalacia. Taken together, our results show a direct influence of the mineralization state of the extracellular matrix surface on differentiation and function of osteoclasts on this surface which may be important for the pathophysiology of osteomalacia and other bone disorders with changed ratio of osteoid to bone.Publicationtype: Journal ArticleScopus© Citations 6 150 161 - Some of the metrics are blocked by yourconsent settings
Item type:Publication, Access status: with files , Developmental transformation and reduction of connective cavities within the subchondral boneIt is widely accepted that the subchondral bone (SCB) plays a crucial role in the physiopathology of osteoarthritis (OA), although its contribution is still debated. Much of the pre-clinical research on the role of SCB is concentrated on comparative evaluations of healthy vs. early OA or early OA vs. advanced OA cases, while neglecting how pure maturation could change the SCB’s microstructure. To assess the transformations of the healthy SCB from young age to early adulthood, we examined the microstructure and material composition of the medial condyle of the femur in calves (three months) and cattle (18 months) for the calcified cartilage (CC) and the subchondral bone plate (SCBP). The entire subchondral zone (SCZ) was significantly thicker in cattle compared to calves, although the proportion of the CC and SCBP thicknesses were relatively constant. The trabecular number (Tb.N.) and the connectivity density (Conn.D) were significantly higher in the deeper region of the SCZ, while the bone volume fraction (BV/TV), and the degree of anisotropy (DA) were more affected by age rather than the region. The mineralization increased within the first 250 µm of the SCZ irrespective of sample type, and became stable thereafter. Cattle exhibited higher mineralization than calves at all depths, with a mean Ca/P ratio of 1.59 and 1.64 for calves and cattle, respectively. Collectively, these results indicate that the SCZ is highly dynamic at early age, and CC is the most dynamic layer of the SCZ.Publicationtype: Journal ArticleScopus© Citations 14 513 349 - Some of the metrics are blocked by yourconsent settings
Item type:Publication, Access status: without files , Matrix demineralisation leads to altered differentiation and function of osteoclasts(Public Library of Science (PLoS), 2015); ; ; ; Publicationtype: Journal Article4 - Some of the metrics are blocked by yourconsent settings
Item type:Publication, Access status: without files , Cementation and interface analysis of early failure cases after hip-resurfacing arthroplasty(Springer, 2012-01-11); ; ; ; Purpose: The use of inappropriate cementation techniques has been suggested as an adverse factor for the long-term survival of hip-resurfacing arthroplasty. Inadequate initial fixation, thermal osteonecrosis and interface biological reactions are possible causes of failure. We analysed morphological changes associated with the cementation technique in a large collection of retrieved femoral components. Methods: One hundred and fifty femoral components (mean time to failure of 8.3 months±11.0) obtained at revision surgery were analysed morphometrically and histopathologically. Cement mantle and penetration were quantified in six different regions of interest. Histopathological analysis of the bone-cement interface was performed on undecalcified processed bone tissue. Results: The vast majority of the cases differed substantially from laboratory-based cement-penetration depth recommendations. Fifty-nine cases had a fibrous membrane at the cement-bone interface. This membrane was significantly thicker in cases with osteonecrosis compared to cases viable bone. Conclusions: Our results demonstrate that most failures were cemented inappropriately. We suggest that poor cementation was an important adverse factor; however, the cause of the failures was obviously multifactorial. The thickness of the fibrous membrane at the cement-bone interface differed significantly between cases with osteonecrosis and specimens with viable bone tissue.Publicationtype: Journal Article8 - Some of the metrics are blocked by yourconsent settings
Item type:Publication, Access status: without files , Improvements in the hip resurfacing surgical technique influence its failure pattern(Science and Education Publishing, 2012); ; ; ; Publicationtype: Journal Article3 - Some of the metrics are blocked by yourconsent settings
Item type:Publication, Access status: without files , 9 - Some of the metrics are blocked by yourconsent settings
Item type:Publication, Access status: without files , Analysis of retrieved hip resurfacing arthroplasties reveals the interrelationship between interface hyperosteoidosis and demineralization of viable bone trabeculae(Elsevier, 2011-12-16); ; ; ; Retrieved hip resurfacing arthroplasties (HRA) revised for causes other than osteonecrosis enable further insights into bone-cement interactions within the interface with only minimal biomechanical stresses. Our primary objective was to investigate the mineralization changes at the trabecular bone interface in retrieved hips using bright field and polarized light microscopy and by quantitative backscattered electron imaging. Because superficial seams of non-mineralized bone tissue varied substantially, we defined hyperosteoidosis as an osteoid seam of more than 20μm thickness. We hypothesized that interface hyperosteoidosis might be caused by the demineralization of previously mineralized bone tissue. One hundred and thirty-one retrieved HRAs with viable bone remnant tissue were analyzed. Bone mineral density distribution obtained from backscattered signal intensities of the trabecular bone at the bone-cement interface was assessed in cases with and without interface hyperosteoidosis. In cases with interface hyperosteoidosis, the degree of trabecular mineralization was also analyzed in deeper areas of the femoral remnants. Thirty-four cases showed hyperosteoidosis at the bone-cement interface, mostly in female patients. Bone trabeculae with hyperosteoidosis displayed a mineral density distribution pattern suggestive of the demineralization of a previously mineralized bone matrix. Our results demonstrate the localized disorder of the mineralization pattern of bone trabeculae at the bone-cement interface in a group of retrieved HRAs. In previously well-fixed femoral components, potential adverse effects on the load-bearing bone due to a decreased degree of mineralization at the bone-cement interface may affect the durability of the implant's function. © 2011 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.Publicationtype: Journal Article185 - Some of the metrics are blocked by yourconsent settings
Item type:Publication, Access status: with files , Sex differences in the morphological failure patterns following hip resurfacing arthroplasty(BioMed Central, 2011-10-13); ; ; ; Background: Metal-on-metal hybrid hip resurfacing arthroplasty (with a cementless acetabular component and a cemented femoral component) is offered as an alternative to traditional total hip arthroplasty for the young and active adult with advanced osteoarthritis. Although it has been suggested that women are less appropriate candidates for metal-on-metal arthroplasty, the mechanisms of prosthesis failure has not been fully explained. While specific failure patterns, particularly osteonecrosis and delayed type hypersensitivity reactions have been suggested to be specifically linked to the sex of the patient, we wished to examine the potential influence of sex, clinical diagnosis, age of the patient and the size of the femoral component on morphological failure patterns in a large cohort of retrieved specimens following aseptic failure of hip resurfacing arthroplasty. Methods: Femoral remnants retrieved from 173 hips with known patient’s sex were morphologically analyzed for the cause of failure. The results were compared with the control group of the remaining 31 failures from patients of unknown sex. The odds ratios (OR) and 95% confidence intervals (CI) of the following morphologically defined variables were calculated using logistic regression analysis: periprosthetic fractures (n = 133), osteonecrosis (n = 151), the presence of excessive intraosseous lymphocyte infiltration (n = 11), and interface hyperosteoidosis (n = 30). Logistic regression analysis was performed both unadjusted and after adjustment for sex, age, the size of the femoral component, and preoperative clinical diagnosis. Results: Femoral remnants from female patients had a smaller OR for fracture (adjusted OR: 0.29, 95% CI 0.11, 0.80, P for difference = 0.02) and for the presence of osteonecrosis (adjusted OR: 0.16, 95% CI 0.04, 0.63, P for difference = 0.01). However, women had a higher OR for both the presence of excessive intraosseous lymphocyte infiltration (adjusted OR: 10.22, 95% CI 0.79, 132.57, P for difference = 0.08) and interface hyperosteoidosis (adjusted OR: 4.19, 95% CI 1.14, 15.38, P for difference = 0.03). Conclusions: Within the limitations of this study, we demonstrated substantial sex differences in distinct failure patterns of metal-on-metal hip resurfacing. Recognition of pathogenically distinct failure modes will enable further stratification of risk factors for certain failure mechanisms and thus affect future therapeutic options for selected patient groups.Publicationtype: Journal ArticleScopus© Citations 14 312 308 - Some of the metrics are blocked by yourconsent settings
Item type:Publication, Access status: without files , Femoral component loosening after hip resurfacing arthroplasty(Springer, 2010-08-01); ; ; ; Objective: Before the re-introduction of the current generation of total hip resurfacing arthroplasty, component loosening and osteolysis were of great concern to the orthopaedic community. Early, mid- and long-term clinical results are encouraging, but component loosening still exists. Materials and Methods: Macroscopic, contact radiographic and histopathological analyses after undecalcified preparation of bone tissue specimens were performed. To investigate the frequency and morphological patterns of the loosening of the femoral component, we analysed a series of 190 retrieved femoral remnants that were revised for aseptic failures. Results: Thirty-five (18.4%) hips were revised for clinical and/or radiographic loosening of the femoral component. Pseudoarthrosis (n=17; median in situ time: 16 weeks, interquartile range [IQR]: 9 to 34), collapsed osteonecrosis (n=5; median in situ time: 79 weeks, IQR: 63 to 97), cement-socket debonding (n=3; median in situ time: 89 weeks, IQR: 54 to 97) and at later follow-up bone-cement loosening (n=10; median in situ time: 175 weeks; IQR 112 to 198; p=0.005) were distinct patterns of the femoral remnant-implant loosening. Fibrocartilaginous metaplasia of interface bone trabeculae (n=38; median in situ time: 61 weeks, IQR: 32 to 138) was strongly associated with femoral component loosening (p=0.009). Both the trabecular hyperosteoidosis (n=32; median in situ time: 71 weeks, IQR 50 to 129) and excessive intraosseous lymphocyte infiltration (n=12; median in situ time: 75 weeks, IQR 51 to 98) at the bone-cement interface correlated strongly with fibrocartilaginous metaplasia (p=0.001 and p=0.016 respectively) and all three lesions were associated with the female gender (p=0.021, p=0.009, and p=0.051). Conclusion: Femoral component loosening at early follow-up was mostly caused by pathological changes of the femoral remnant bone tissue: pseudoarthrosis and collapsed osteonecrosis. Fibrocartilaginous metaplasia was frequently observed in hips with femoral component loosening. The potential role of interface hyperosteoidosis as a precursor lesion of bone-cement loosening and its possible association with delayed type hypersensitivity reaction are discussed. © 2010 ISS.Publicationtype: Journal Article4 - Some of the metrics are blocked by yourconsent settings
Item type:Publication, Access status: without files , Morphologic analysis of periprosthetic fractures after hip resurfacing arthroplasty(Wolters Kluwer Health, 2010-02-01); ; ; ; Domarus, Christoph vonBackground: Periprosthetic fractures have long been recognized as one of the major complications of hip resurfacing arthroplasty. The objective of this study was to develop a systematic and morphologic classification of the fracture mode based on pathogenesis. Methods: One hundred and seven retrieved specimens consisting of the femoral remnant and the femoral component of a total hip resurfacing arthroplasty that had failed as a result of a periprosthetic fracture were analyzed with regard to the morphologic failure mode. The location of the fracture line was used to differentiate the fractures. The fractures were also classified histopathologically as acute biomechanical, acute postnecrotic, or chronic biomechanical. Results: Fifty-nine percent (sixty-three) of the fractures occurred within the bone inside the femoral component. Fifty-one percent (fifty-five) of the fractures were classified morphologically as acute postnecrotic; 40% (forty-three), as chronic biomechanical; and 8% (nine), as acute biomechanical. Acute biomechanical fractures were found exclusively in the femoral neck and occurred earlier (mean time [and standard deviation] between implantation and revision, 41 ± 57 days) than acute postnecrotic fractures (mean time between implantation and revision, 149 ± 168 days; p = 0.002) or chronic biomechanical fractures (mean time between implantation and revision, 179 ± 165 days; p = 0.001). The latter two fracture types both occurred predominantly in the bone inside the femoral component. Conclusions: Three distinct fracture modes were characterized morphologically. Osteonecrosis was the most frequent cause of fracture-related failures. We suggest that an intraoperative mechanical injury of the femoral neck such as notching and/or malpositioning of the femoral component might lead to changes in the loading pattern or in the resistance to fracture of the femoral neck and may result in both acute and chronic biomechanical femoral neck fractures. These findings may serve as feedback information for the surgeon and possibly influence future therapeutic strategies.Publicationtype: Journal Article4