Critical illness-related bone loss is associated with osteoclastic and angiogenic abnormalities
Article
Owen, H., Vanhees, I., Solie, L., Roberts, S., Wauters, A., Luyten, F., Van Cromphaut, S. and Van den Berghe, G. 2012. Critical illness-related bone loss is associated with osteoclastic and angiogenic abnormalities. Journal of Bone and Mineral Research. 27 (7), pp. 1541-1552. https://doi.org/10.1002/jbmr.1612
| Type | Article |
|---|---|
| Title | Critical illness-related bone loss is associated with osteoclastic and angiogenic abnormalities |
| Authors | Owen, H., Vanhees, I., Solie, L., Roberts, S., Wauters, A., Luyten, F., Van Cromphaut, S. and Van den Berghe, G. |
| Abstract | Critically ill patients are at increased risk of fractures during rehabilitation, and can experience impaired healing of traumatic and surgical bone fractures. In addition, markers of bone resorption are markedly increased in critically ill patients, while markers of bone formation are decreased. In the current study, we have directly investigated the effect of critical illness on bone metabolism and repair. In a human in vitro model of critical illness, Fluorescence-activated cell sorting (FACS) analysis revealed an increase in circulating CD14+/CD11b+ osteoclast precursors in critically ill patient peripheral blood compared to healthy controls. In addition, the formation of osteoclasts was increased in patient peripheral blood mononuclear cell (PBMC) cultures compared to healthy controls, both in the presence and absence of osteoclastogenic factors receptor activator of NF-κB ligand (RANKL) and macrophage colony-stimulating factor (M-CSF). Culturing PBMCs with 10% critically ill patient serum further increased osteoclast formation and activity in patient PBMCs only, and neutralization studies revealed that immunoglobulin G (IgG) antibody signaling through the immunoreceptor Fc receptor common γ chain III (FcRγIII) played an important role. When analyzing bone formation, no differences in osteogenic differentiation were observed using human periosteal-derived cells (hPDCs) treated with patient serum in vitro, but a decrease in the expression of vascular endothelial growth factor receptor 1 (VEGF-R1) suggested impaired vascularization. This was confirmed using serum-treated hPDCs implanted onto calcium phosphate scaffolds in a murine in vivo model of bone formation, where decreased vascularization and increased osteoclast activity led to a decrease in bone formation in scaffolds with patient serum-treated hPDCs. Together, these findings may help to define novel therapeutic targets to prevent bone loss and optimize fracture healing in critically ill patients. |
| Keywords | critical illness; peripheral blood mononuclear cells; osteoclasts; FcRγIII; human periosteal-derived cells |
| Publisher | Wiley |
| American Society for Bone and Mineral Research | |
| Journal | Journal of Bone and Mineral Research |
| ISSN | 0884-0431 |
| Electronic | 1523-4681 |
| Publication dates | |
| Online | 15 Jun 2012 |
| 01 Jul 2012 | |
| Publication process dates | |
| Deposited | 21 Apr 2016 |
| Accepted | 12 Mar 2012 |
| Output status | Published |
| Digital Object Identifier (DOI) | https://doi.org/10.1002/jbmr.1612 |
| PubMed ID | 22461003 |
| Web of Science identifier | WOS:000305297000014 |
| Language | English |
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