Effect of recent spinal cord injury on the OPG/RANKL system and its relationship with bone loss and the response to denosumab therapy
There is marked bone loss after spinal cord injury (SCI); however, its pathogenesis and clinical management remain unclear. The increased circulating levels of receptor activator of nuclear factor kB ligand (RANKL) associated with bone loss shortly after SCI and the prevention of bone loss with denosumab treatment suggest a contributory role of RANKL in SCI-induced osteoporosis.
Bone turnover and bone loss are markedly increased shortly after SCI. However, the pathogenesis and clinical management of this process remain unclear, especially the role of the osteoprotegerin (OPG)/RANKL system in this disorder. The aim of this study was to analyze serum levels of OPG and RANKL in bone loss associated with recent SCI and the effect of denosumab treatment on these mediators.
Twenty-three males with recent complete SCI were prospectively included. Serum OPG and RANKL levels, bone turnover markers (PINP, bone ALP, CTX), and bone mineral density (BMD) were assessed at baseline, at 6 months of follow-up, prior to initiating denosumab, and 6 months after treatment. The results were compared with a healthy control group.
At baseline, SCI patients showed higher RANKL levels vs. controls which were correlated with days-since-SCI and total hip BMD loss at 6 months. OPG levels were similar to controls at baseline. After denosumab treatment, OPG showed no changes, whereas RANKL levels became undetectable in 67% of patients. Patients with undetectable RANKL during treatment showed better response in femoral BMD and bone markers vs. patients with detectable RANKL at 6 months of denosumab. Increased parathormone (PTH) levels during treatment were negatively correlated with RANKL changes.
RANKL levels are increased after SCI and related to BMD loss at the proximal femur, becoming undetectable after denosumab treatment. The effect of denosumab on preventing sublesional bone loss, especially in patients with undetectable levels during treatment, suggests a contributory role of RANKL in this process.
Publisher URL: https://link.springer.com/article/10.1007/s00198-017-4090-4
Keeping up-to-date with research can feel impossible, with papers being published faster than you'll ever be able to read them. That's where Researcher comes in: we're simplifying discovery and making important discussions happen. With over 19,000 sources, including peer-reviewed journals, preprints, blogs, universities, podcasts and Live events across 10 research areas, you'll never miss what's important to you. It's like social media, but better. Oh, and we should mention - it's free.
Researcher displays publicly available abstracts and doesn’t host any full article content. If the content is open access, we will direct clicks from the abstracts to the publisher website and display the PDF copy on our platform. Clicks to view the full text will be directed to the publisher website, where only users with subscriptions or access through their institution are able to view the full article.