Back pain affects millions of people and can make everyday activities such as walking, sitting, working and sleeping difficult.
New research suggests that changes in gene activity may help explain why the soft discs between the bones of the spine gradually become damaged and unusually hard.
The study was carried out by researchers from the Universities of Edinburgh and Bristol and was published in the journal Communications Biology.
The work was funded by Arthritis UK and the Biotechnology and Biological Sciences Research Council.
The spine is made of a series of bones called vertebrae. Between most of these bones are flexible discs that act like cushions, helping the spine absorb pressure and move smoothly.
These discs contain strong structural proteins and water-rich tissue that allow them to handle repeated bending, twisting and compression. With age or disease, however, the discs can gradually lose their normal structure and function.
This process is known as intervertebral disc degeneration. It is a common contributor to back and neck pain, although disc changes seen on scans do not always cause pain and many people with degeneration have few or no symptoms.
Genes are one factor that can influence a person’s risk of disc disease. Previous studies have linked early disc problems with genes involved in collagen IX, a protein that helps support the network of fibers inside spinal discs.
To investigate how this genetic connection might lead to damage, the researchers turned to zebrafish. These small fish are widely used in biomedical research because many of their genes and basic biological processes are shared with humans.
The team studied zebrafish that lacked a working copy of a gene involved in collagen IX. As the fish aged, their spines developed changes that resembled important features of human disc degeneration.
The tissue between vertebrae began to harden as minerals accumulated where they normally should not. Eventually, some vertebrae fused together, reducing the normal separation between the bones.
Importantly, mineral buildup was not the first change the researchers observed. Before hardening occurred, a supportive structural layer in the developing spine began to break down.
This suggests that the disease may unfold in stages. Early damage to the tissue’s supporting framework may create conditions that later allow abnormal mineral deposits to form.
The researchers then examined which genes were more or less active in the affected fish. This allowed them to identify biological systems that changed as the spinal disease developed.
Several stood out. The team found changes in the way the body processed fats, as well as changes involving mTOR, a major system that helps cells control growth, nutrients and energy.
They also identified changes in phosphate control and vitamin A signaling. These processes are important because the balance of minerals and nutrients helps determine when and where hard mineral tissue forms in the body.
Phosphate is essential for healthy bones, but it needs to be carefully controlled. When mineral regulation goes wrong, calcium and phosphate can accumulate in soft tissues where they do not belong.
The researchers then tested whether interfering with some of these pathways could reduce the spinal changes. One experiment used a bisphosphonate, a type of medicine already prescribed to people with osteoporosis and some other bone conditions.
In the zebrafish, the bisphosphonate reduced abnormal mineral buildup. This is interesting because medicines that already have a known clinical use can sometimes be investigated for new purposes more quickly than completely new drugs.
Other experiments pointed toward metabolism as another possible target. Spinal fusion was reduced when the fish received less food or when researchers used drugs that reduced fat metabolism.
These results suggest that the way cells handle nutrients and fats may influence whether damaged spinal tissue begins to mineralize. The researchers highlighted phosphate regulation and fat metabolism as promising areas for future study.
Dr. Erika Kague of the University of Edinburgh’s Institute of Genetics and Cancer, who led the research, said understanding why spinal tissue hardens could reveal ways to slow the process. The team believes zebrafish could also provide a useful system for testing possible treatments.
The findings are encouraging because there is currently no medicine proven to reverse established intervertebral disc degeneration. Treatment for back pain can include exercise, physical therapy, pain medicines and other approaches, while surgery is reserved for selected patients with severe structural or nerve problems.
However, the study should not be interpreted as showing that an osteoporosis drug can already treat ordinary back pain in people. The experiments were performed in genetically altered zebrafish, and a fish spine is not identical to the much larger and mechanically complex human spine.
The genetic model also represents one specific route to disc damage. Human back pain can arise from many causes, including muscle and ligament problems, arthritis, nerve compression, injuries and age-related changes.
Another important point is that reducing food intake in fish is not evidence that people should restrict food to treat disc disease. That experiment helps researchers understand metabolism, but translating it into a safe human therapy requires much more work.
The study’s major strength is that it follows a chain of events from a genetic defect to structural damage, altered gene activity and abnormal mineralization. It also identifies several biological pathways that can be manipulated experimentally.
Overall, the Communications Biology study offers new clues rather than an immediate treatment. Its most promising contribution is the identification of mineral control and fat metabolism as processes that may be involved in spinal hardening.
If future studies confirm that similar mechanisms operate in human discs, researchers may eventually be able to develop medicines that slow degeneration before severe damage occurs.
That would represent an important change from treating the consequences of advanced spinal disease toward targeting the biology that drives it.
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