Wear of hip prostheses increases serum IGFBP-1 levels in patients with aseptic loosening

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.This work was supported by Grant RTI2018-095159-B-I00 from the Spanish Ministry of Science, Innovation and Universities (MCINN) and Grant PI18/00643 from Instituto de Salud Carlos III (ISCIII)-Fondo Europeo de Desarrollo Regional (FEDER) and the Spanish Ministry of Economy and Competitiveness (MINECO-AES). LS is supported by a Miguel Servet contract from ISCIII-MINECO-AES-FEDER-FSE. NV is supported by Program I2 from the Regional Government of Madrid. The authors are indebted to Fatima Bensiamar (IdiPAZ and CIBER-BBN) for her excellent technical assistance with the cell culture experiments and gene expression analysis and to the Cell Culture Core Facilities of IdiPAZ