Title: Vertebral osteomyelitis is characterised by increased RANK/OPG and RANKL/OPG expression ratios in vertebral bodies and intervertebral discs

Authors: S Lang, M Loibl, J Gläsner, M Simon, M Rupp, S Grad, C Neumann, V Alt, A Gessner, F Hanses

Address: Department of Trauma Surgery, University Hospital Regensburg, Franz-Josef-Strauss Allee 11, D-93053 Regensburg, Germany

E-mail: markus.loibl at gmail.com

Abstract: Vertebral osteomyelitis (VO) is an infection of the spine mainly caused by bacterial pathogens. The pathogenesis leading to destruction of intervertebral discs (IVDs) and adjacent vertebral bodies (VBs) is poorly described. The present study aimed at investigating the connection between infection and bone/disc metabolism in VO patients.
14 patients with VO (infection group) and 14 patients with burst fractures of the spine (fracture group; control) were included prospectively. Tissue biopsies from affected IVDs and adjacent VBs were analysed by RT-qPCR for mRNA-expression levels of 18 target genes including chemokines, adipokines and genes involved in bone metabolism.
Most importantly, the receptor activator of NF-κB/osteoprotegerin (RANK/OPG) expression ratio was drastically elevated in both VBs and IVDs of the infection group. In parallel, expression of genes of the prostaglandin-E2-dependent prostanoid system was induced. Such genes regulate tissue degradation processes via the triad OPG/RANK/RANKL as well as via the chemokines IL-8 and CCL-20, whose expression was also found to be increased upon infection. The gene expression of the adipokine leptin, which promotes inflammatory tissue degradation, was higher in IVD tissue of the infection group, whereas the transcription of omentin and resistin genes, whose functions are largely unknown in the context of infectious diseases, was lower in infected VBs.
In summary, similar expression patterns of pro-inflammatory cytokines and pro-osteoclastogenic factors were identified in VBs and IVDs of patients suffering from VO. This suggests that common immuno-metabolic pathways are involved in the mechanisms leading to tissue degradation in VBs and IVDs during VO.

Key Words: Vertebral osteomyelitis, signalling molecules-cytokines, adipokines, cells/tissues-intervertebral disc, infection-in vivo, spine-vertebral body, osteoimmunity, RANK/RANKL/OPG.

Publication date: November 30th 2021

Article download: Pages 438-451 (PDF file)
DOI: 10.22203/eCM.v042a27