Development of an immunoassay panel to predict aseptic implant loosening

• Main Author: Ramchandra Desai, Suchita
• Format: Others
• Language: English
• Published: Högskolan i Skövde, Institutionen för biovetenskap 2018
• Subjects: Osteoclasts; M1 macrophage; M2 macrophage; Parathyroid hormone; RANKL; Calcium; TRAP; monocytes; FBGCs; ELISA; Biological Sciences; Biologiska vetenskaper
• Online Access: http://urn.kb.se/resolve?urn=urn:nbn:se:his:diva-16285

During our lifetime, our bones constantly go through remodelling to maintain the skeletal system. This is done by osteoblasts that deposit new bone tissue, osteoclasts that remove the bone matrix and mechanosensing osteocytes. In case of bone implants, increased resorption by osteoclasts due to inflammation (inflammatory osteolysis) leads to aseptic implant loosening. This study focuses on how to detect these inflammatory resorbing cells at an early stage and prevent their activity with appropriate medication. To achieve this, we differentiated classical monocytes into macrophage-like cells, osteoclasts(OCs) and foreign body giant cells (FBGC) and their secretome was studied to identify specific biomarkers. Previously, tartrate resistant acid phosphatase (TRAP) was studied as an important biomarker for OCs and macrophages. An ELISA to separate and quantitate the two TRAP isoforms was used to distinguish the resorbing OCs from inflammatory FBGCs on the basis of the isoform ratio. This assay gave high levels of 5b isoform for osteoclastic stimulation and high 5a levels for the inflammatory stimulation. Also, different aminothiazole inhibitors were tested which were shown to be efficient drugs in inhibiting inflammatory osteolysis by reducing osteoclast formation and resorption in sub-micromolar concentration. Further to apply this study to patient samples, an immunoassay panel can be developed which will help detect TRAP and multiple biomarkers like CTX specific to aseptic loosening simultaneously. This will help in early, efficient and accurate diagnosis of inflammatory osteolytic bone loss and provide us with an accurate diagnosis and sufficient time for appropriate treatment.