Findings from a study in zebrafish suggest that changes in gene activity can lead to a build-up of minerals in the spine – similar to unwanted bone forming in the wrong place – causing it to harden.
Experts say the findings point to potential future drug targets to treat back pain and suggest zebrafish could be a valuable tool for testing them.
Disc degeneration
Back pain affects most people at some point in their lives. One of the main underlying causes is the gradual breakdown of spinal discs – which cushion the bones of the spine – known as intervertebral disc degeneration (IVDD).
Despite how common and costly IVDD is, there are currently no drugs that can stop or reverse the condition. Surgery remains the only long-term option.
Gene study
Genetics are known to play a role in the development of IVDD. A gene connected to a protein called collagen IX – which helps hold the disc's structural fibres together – has been repeatedly linked to early-onset disc problems.
Scientists from the Universities of Edinburgh and Bristol studied zebrafish that were bred to lack a working copy of the gene to better understand how genetic faults could lead to disc disease.
Mineral build-up
As the fish aged, their spines developed problems strikingly similar to human disc disease. The bones of the spine fused together and the tissue between vertebrae became abnormally hardened with mineral deposits.
The team found that this hardening was preceded by a breakdown in a supportive scaffold layer in the developing spine, well before any mineral began to build up.
Researchers looked at which genes were switched on or off in the fish. They uncovered disruptions to how the body handles fat and to a growth-control pathway called mTOR, alongside changes in phosphate handling and vitamin A signalling – all processes linked to mineral build-up.
Potential treatments
Excitingly, they were also able to demonstrate ways to reduce the damage. A bone-protecting drug already used for osteoporosis – known as a bisphosphonate – blocked the mineral build-up. Simply restricting the fish's food intake, or using drugs that dampen fat metabolism, also reduced spinal fusions.
The findings point to phosphate handling and fat metabolism as promising targets for future drugs, experts say.