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The biological mechanisms involved in aseptic loosening include inflammation-associated and bone resorption-associated processes. Coordinated cellular actions result in biochemical imbalances with devastating consequences for the joint. Given that this condition is not known for showing systemic signs, we investigated whether circulating levels of inflammation-related proteins are altered in patients with aseptic loosening. Our study included 37 patients who underwent revision surgery due to hip osteolysis and aseptic loosening and 31 patients who underwent primary total hip arthroplasty. Using antibody arrays, we evaluated the serum levels of 320 proteins in four patients from each group. The results showed differences in insulin-like growth factor-binding protein 1 (IGFBP-1) concentrations, which we then quantified using enzyme-linked immunosorbent assay tests in all study patients. The results confirmed that serum IGFBP-1 concentrations were higher in the revision surgery patients than in the hip arthroplasty patients. In vitro studies showed that exposure of human osteoblasts to titanium particles induced an IGFBP-1 release that further increased when exposure to particles was performed in media conditioned by human M1 macrophages. These findings suggest that elevated serum IGFBP-1 levels in patients with aseptic loosening can arise from increased local IGFBP-1 production in the inflammatory environment of the periprosthetic bed. [ABSTRACT FROM AUTHOR]

Background: The preoperative bone defect and the reconstruction of the center of rotation of the hip are critical in acetabular revision surgery. Uncemented oblong cups are employed in order to manage these issues. We analyzed the clinical results and rates of revision of two different uncemented oblong cups, the reconstruction of the center of rotation of the hip, as well as the rate of radiological loosening and possible risk factors. Materials and methods: Forty-five patients (46 hips) underwent acetabular revision surgery using two different uncemented oblong cups. We assessed the clinical results and the survival rate for revision and aseptic loosening. Intraoperative bone loss was classified according to Paprosky, and acetabular reconstruction was assessed according to Ranawat. The mean follow-up was 7.2 years (range 4-11 years). Results: There were four re-revisions (three due to aseptic loosening); the survival rate for re-revision due to aseptic loosening was 60.1 % at seven years. The mean distance between the center of the femoral head prosthesis and the approximate center of the femoral head improved from 21.5 to 10.2 mm. Thirteen cups showed radiological loosening; the survival rate for radiological loosening at seven years was 40.54 %. A smaller postoperative horizontal distance was correlated with cup loosening. Conclusions: Although optimal acetabular reconstruction can be achieved by using oblong uncemented cups in revision hip surgery, the clinical and radiological results are not encouraging. Excessive medialization of the cup may increase the rate of loosening. [ABSTRACT FROM AUTHOR]

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Mesenchymal stem cells (MSC) modulate the macrophage-mediated inflammatory response through the secretion of soluble factors. In addition to its classical effects on calcium homeostasis, 1,25-dihydroxyvitamin D3 (1,25D3) has emerged as an important regulator of the immune system. The present study investigates whether 1,25D3 modulates the paracrine interactions between MSC and macrophages. 1,25D3 stimulated MSC to produce PGE2 and VEGF and regulated the interplay between macrophages and MSC toward reduced pro-inflammatory cytokine production. Conditioned media (CM) from co-cultures of macrophages and MSC impaired MSC osteogenesis. However, MSC cultured in CM from 1,25D3-treated co-cultures showed increased matrix maturation and mineralization. Co-culturing MSC with macrophages prevented the 1,25D3-induced increase in RANKL levels, which correlated with up-regulation of OPG secretion. MSC seeding in three-dimensional (3D) substrates potentiated their immunomodulatory effects on macrophages. Exposure of 3D co-cultures to 1,25D3 further reduced the levels of soluble factors related to inflammation and chemotaxis. As a consequence of 1,25D3 treatment, the recruitment of monocytes toward CM of 3D co-cultures decreased, while the osteogenic maturation of MSC increased. These data add new insights into the pleiotropic effects of 1,25D3 on the crosstalk between MSC and macrophages and highlight the role of the hormone in bone regeneration. [ABSTRACT FROM AUTHOR]