Advances

Advances in Orthopedics

Intervertebral Disc Disease: Identifying Factors Related to Severity

Studies in the Department of Orthopedic Surgery at Columbia are seeking to identify biomarkers to determine disease activity and accurately predict response to treatment.

Research faculty in the Department of Orthopedic Surgery at Columbia University Vagelos College of Physicians and Surgeons are applying tools of bioengineering, cell and tissue biomechanics, and animal physiology to study the function of the disc and disc cells, emphasizing degenerative and inflammatory processes. They seek to understand how biomechanics and the mechanobiology of cells and tissues cause a healthy spine to degenerate. The variability in the response of patients to treatment is of particular interest. What is present in a patient’s circulation that is contributing to their disease state? The answer may be found in identifying biomarkers to stratify patients for treatment – medical or surgical – and ultimately achieve better efficacy and outcomes for those patients.

The Important Role of Inflammation

The researchers hypothesize that inflammation is a driving force of spinal disc degeneration and associated pain propagation. Supported by NIH R01 funding, Nadeen O. Chahine, PhD, Associate Professor of Bioengineering in Orthopedic Surgery and Biomedical Engineering at Columbia University, has been investigating the role of inflammation in disc degeneration. Dr. Chahine believes there are consequences of inflammation that are detrimental to mechanical functions of the disc and therefore need to be addressed at the cellular and molecular level.

Her lab has developed an animal model, using direct intradiscal stimulation of innate immunity in the intervertebral disc, to explore the role of inflammation in triggering degeneration. They have found that inflammatory insults alone, in the absence of traumatic injury, triggers degeneration of the intervertebral disc. These findings are physiologically relevant. With the identification of a chemical trigger and disease mechanism of degeneration that mimics the molecular profile of human disc degeneration, they have uncovered a target that may be amenable to pharmacological treatments and are now evaluating potential inhibitors of these pathways for the treatment of intervertebral disc degeneration.

Identifying Biomarkers to Enable Targeted Treatment

In collaboration with spine surgeons and rehabilitation medicine specialists at NewYork-Presbyterian/Columbia, Dr. Chahine is investigating potential systemic biomarkers of intervertebral disc disease severity and back pain. They are looking at patients with lumbar disc herniation whose treatments range from epidural steroid injections to surgery. The researchers are evaluating patient-reported outcome measures, including severity of pain and level of disability, and modeling this information with levels of biomarkers measured in blood specimens pre- and post-treatment. Based on changes in specific profiles of inflammatory mediators, they are seeking to determine which factors are predictive of change in outcomes. Patients who move on to surgery continue in the study and all patients are followed longitudinally up to one year.

Dr. Chahine notes that by analyzing inflammatory biomarkers and phenotyping patients based on inflammation, they have already learned that the inflammatory profiles are very different in different kinds of spine conditions. For example, patients who have spinal stenosis and degenerative disc disease have a far higher inflammatory burden in their blood systemically compared to patients who have, for example, disc herniation. And all of the patients with low back pain have inflammatory levels that are far worse than a controlled cohort of patients with no history of back pain.

Over 200 clinical subjects have been enrolled and preliminary findings reinforce that back pain patients have elevated systemic inflammation in a manner that depends on the diagnosis of the disc pathology. These findings confirm their hypothesis that inflammation is a driving force of pain propagation associated with spinal degeneration. They have identified a profile of mediators that are correlated with improvement in pain and disability with epidural steroid injection treatments. Their work suggests that identifying markers to accurately predict response to treatment may become an additional diagnostic tool to spine radiological examinations.

On a parallel track to understand disease severity and pain, Dr. Chahine and her colleagues recently reported on a study they conducted that is the first to show that disc herniation severity is coordinately associated with changes in serum levels of inflammatory cytokines in chronic pain subjects.

Read more at: https://www.oarsijournal.com/article/S1063-4584(20)31060-8/fulltext