Sex differences in the morphological failure patterns following hip resurfacing arthroplasty

<p>Abstract</p> <p>Background</p> <p>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.</p> <p>Methods</p> <p>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.</p> <p>Results</p> <p>Femoral remnants from female patients had a smaller OR for fracture (adjusted OR: 0.29, 95% CI 0.11, 0.80, <it>P </it>for difference = 0.02) and for the presence of osteonecrosis (adjusted OR: 0.16, 95% CI 0.04, 0.63, <it>P </it>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, <it>P </it>for difference = 0.08) and interface hyperosteoidosis (adjusted OR: 4.19, 95% CI 1.14, 15.38, <it>P </it>for difference = 0.03).</p> <p>Conclusions</p> <p>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.</p

Adult Osteosclerotic Metaphyseal Dysplasia With Progressive Osteonecrosis of the Jaws and Abnormal Bone Resorption Pattern Due to a LRRK1 Splice Site Mutation

Osteosclerotic metaphyseal dysplasia (OSMD) is a rare autosomal recessive sclerosing skeletal dysplasia. We report on a 34-year-old patient with sandwich vertebrae, platyspondyly, osteosclerosis of the tubular bones, pathologic fractures, and anemia. In the third decade, he developed osteonecrosis of the jaws, which was progressive in spite of repeated surgical treatment over a period of 11 years. An iliac crest bone biopsy revealed the presence of hypermineralized cartilage remnants, large multinucleated osteoclasts with abnormal morphology, and inadequate bone resorption typical for osteoclast-rich osteopetrosis. After exclusion of mutations in TCIRG1 and CLCN7 we performed trio-based exome sequencing. The novel homozygous splice-site mutation c.261G>A in the gene LRRK1 was found and co-segregated with the phenotype in the family. cDNA sequencing showed nearly complete skipping of exon 3 leading to a frameshift (p.Ala34Profs*33). Osteoclasts differentiated from the patient's peripheral blood monocytes were extremely large. Instead of resorption pits these cells were only capable of superficial erosion. Phosphorylation of L-plastin at position Ser5 was strongly reduced in patient-derived osteoclasts showing a loss of function of the mutated LRRK1 kinase protein. Our analysis indicates a strong overlap of LRRK1-related OSMD with other forms of intermediate osteopetrosis, but an exceptional abnormality of osteoclast resorption. Like in other osteoclast pathologies an increased risk for progressive osteonecrosis of the jaws should be considered in OSMD, an intermediate form of osteopetrosis

Osteoidosis leads to altered differentiation and function of osteoclasts

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

Applied system analysis and technology of designing the software

An analogy is made between the stages of applied system analysis and the stages of software Engineerin

Negative Regulation of Bone Formation by the Transmembrane Wnt Antagonist Kremen-2

Wnt signalling is a key pathway controlling bone formation in mice and humans. One of the regulators of this pathway is Dkk1, which antagonizes Wnt signalling through the formation of a ternary complex with the transmembrane receptors Krm1/2 and Lrp5/6, thereby blocking the induction of Wnt signalling by the latter ones. Here we show that Kremen-2 (Krm2) is predominantly expressed in bone, and that its osteoblast-specific over-expression in transgenic mice (Col1a1-Krm2) results in severe osteoporosis. Histomorphometric analysis revealed that osteoblast maturation and bone formation are disturbed in Col1a1-Krm2 mice, whereas bone resorption is increased. In line with these findings, primary osteoblasts derived from Col1a1-Krm2 mice display a cell-autonomous differentiation defect, impaired canonical Wnt signalling and decreased production of the osteoclast inhibitory factor Opg. To determine whether the observed effects of Krm2 on bone remodeling are physiologically relevant, we analyzed the skeletal phenotype of 24 weeks old Krm2-deficient mice and observed high bone mass caused by a more than three-fold increase in bone formation. Taken together, these data identify Krm2 as a regulator of bone remodeling and raise the possibility that antagonizing KRM2 might prove beneficial in patients with bone loss disorders

Paraffinoma of lips and oral mucosa: Case report and brief review of the literature

Interstitial application of paraffin in plastic and reconstructive surgery is obsolete due to the development of permanent and extensive foreign body granulomas at the site of application. These granulomas can cause severe physical impairment and develop their own prognostic worth. Furthermore, the disperse oil droplets are not a locally stable suspension. Therefore, the desired aesthetic aspect can get lost in the course of a potential dislocation of the suspension. In addition, the interstitial confluence of non-resorbable droplets to larger oil drops causes palpable and sometimes visible indurations of the skin, the correlate of chronic inflammation. This case report describes the efforts undertaken to release the patient at least temporarily from her paraffin granulomas and to improve her appearance. The relevant literature is briefly discussed. Furthermore, we present some immunohistochemical findings to specify the foreign body reaction associated with paraffin injections into connective tissues