Role of Wnt/β-catenin and RANKL/OPG in bone healing of diabetic Charcot arthropathy patients
DOI:
https://doi.org/10.3109/17453674.2015.1033606Abstract
Background and purpose — Charcot neuropathy is characterized by bone destruction in a foot leading to deformity, instability, and risk of amputation. Little is known about the pathogenic mechanisms. We hypothesized that the bone-regulating Wnt/β-catenin and RANKL/OPG pathways have a role in Charcot arthropathy. Patients and methods — 24 consecutive Charcot patients were treated by off-loading, and monitored for 2 years by repeated foot radiography, MRI, and circulating levels of sclerostin, dickkopf-1, Wnt inhibitory factor-1, Wnt ligand-1, OPG, and RANKL. 20 neuropathic diabetic controls and 20 healthy controls served as the reference. Results — Levels of sclerostin, Dkk-1 and Wnt-1, but not of Wif-1, were significantly lower in Charcot patients than in the diabetic controls at inclusion. Dkk-1 and Wnt-1 levels responded to off-loading by increasing. Sclerostin levels were significantly higher in the diabetic controls than in the other groups whereas Wif-1 levels were significantly higher in the healthy controls than in the other groups. OPG and RANKL levels were significantly higher in the Charcot patients than in the other groups at inclusion, but decreased to the levels in healthy controls at 2 years. OPG/RANKL ratio was balanced in all groups at inclusion, and it remained balanced in Charcot patients on repeated measurement throughout the study. Interpretation — High plasma RANKL and OPG levels at diagnosis of Charcot suggest that there is high bone remodeling activity before gradually normalizing after off-loading treatment. The consistently balanced OPG/RANKL ratio in Charcot patients suggests that there is low-key net bone building activity by this pathway following diagnosis and treatment. Inter-group differences at diagnosis and changes in Wnt signaling following off-loading treatment were sufficiently large to be reflected by systemic levels, indicating that this pathway has a role in bone remodeling and bone repair activity in Charcot patients. This is of particular clinical relevance considering the recent emergence of promising drugs that target this system.Downloads
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Published
2015-07-04
How to Cite
Folestad, A., Ålund, M., Asteberg, S., Fowelin, J., Aurell, Y., Göthlin, J., & Cassuto, J. (2015). Role of Wnt/β-catenin and RANKL/OPG in bone healing of diabetic Charcot arthropathy patients. Acta Orthopaedica, 86(4), 415–425. https://doi.org/10.3109/17453674.2015.1033606
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Acta Orthopaedica (Scandinavica) content is available freely online as from volume 1, 1930. The journal owner owns the copyright for all material published until volume 80, 2009. As of June 2009, the journal has however been published fully Open Access, meaning the authors retain copyright to their work. As of June 2009, articles have been published under CC-BY-NC or CC-BY licenses, unless otherwise specified.