Analysis of the serum Receptor Activator of NF-κB Ligand/Osteoprotegerin ratio (RANKL/OPG ratio) as potential marker for infection-related bone destruction in pyogenic vertebral osteomyelitis.

• Applicant: Dr. Siegmund Lang
• Subject Area: Orthopaedics, Traumatology, Reconstructive Surgery
• Term: since 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 518780143

Vertebral Osteomyelitis (VO) is associated with relevant morbidity and high rates or mortality. Bone homeostasis is regulated by the Receptor activator of NF-κB Ligand/Osteoprotegerin (RANK/RANKL/OPG) axis.Circulating soluble OPG (sOPG) and soluble RANKL (sRANKL) serum levels have been suggested as biomarkers for bone metabolism. sRANKL/sOPG ratio is a potential surrogate marker for the bone-turnover and progress of infectious osteolysis of VO. Besides the potential implication of the sRANKL/sOPG ratio as a serum marker in metabolic bone disease, the role of this biomarker in VO has not been studied yet. Therefore, the purpose of the current project is to elucidate the role and potential of sRANKL/sOPG ratio to determine bone loss in VO. This could help to identify patients at risk for subsequent bone loss that would benefit from early spine surgery. The primary objective of the current project is to compare sRANKL/sOPG ratio in all prospectivley included patients with pyogenic vertebral osteomyelitis in relation to the amount of bone destruction at time of initial diagnosis. Bone destruction will be determined by 3D volumetry of the affected vertebral bodies. The hypothesis is that patients with high amount of intial bone loss have higher sRANKL/sOPG ratios compared to patients with low amount of inital bone loss. Secondary objective of the current project is to use the sRANKL/sOPG ratio to identify patients at risk for subsequent bone loss in VO during non-surgical treatment within 12 weeks who had only low amount bone loss at baseline. The hypothesis is that patients with initial low amount bone loss that have progressive vertebral bone loss within the observation period of 12 weeks have differences in the course of the sRANKL/sOPG ratios compared to patients without further bone loss. Progressive vertebral bone loss is defined as any loss of height in vertebral body height or progress in kyphosis in the lateral radiological view of the infected spinal segment during the observation period. Lastly the proposed study aims to compare sRANKL/sOPG ratio versus local RANKL/OPG ratio from bone samples ratio in surgically treated VO patients. For this, intraoperative samples from the affected vertebrae will be harvested for rt-PCR, immunostaining and histomorphometry from patients that have to undergo surgical treatment. The hypothesis is that there is a correlation between serum RANKL/OPG and local RANKL/OPG ratio and bone turnover.

• DFG Programme: Research Grants