Back Pain: Osteoporosis Drug Slows Spinal Ossification

Back pain is one of the few widespread conditions medicine still cannot cure, only operate on. A team from the University of Edinburgh and the University of Bristol published a paper on August 6 in the journal Communications Biology that offers the first concrete lead toward something else: in fish, a bisphosphonate, a drug already prescribed against osteoporosis, blocked mineral buildup in the spine.

The condition in question is intervertebral disc degeneration, the gradual breakdown of the cushions sitting between vertebrae. Discs absorb the load placed on the spine, and when they fail, back pain and neck pain follow. Hereditary factors have long been part of this story, and one gene stands out: the one carrying instructions for collagen IX, a protein that holds the disc’s fibrous structure together. Earlier research has repeatedly linked it to early disc problems.

A Fish With One Gene Switched Off

Researchers took the zebrafish, a small aquarium species, and bred a line missing a working copy of the col9a1b gene. As the fish aged, their spines began to resemble the human disc disease. Vertebrae fused together, and the tissue between the bones grew abnormally hard from mineral deposits.

The order of events matters. Hardening was preceded by the breakdown of a supporting layer in the still developing spine, well before the first mineral appeared. The damage, in other words, does not start with deposits building up, but with the support giving way first.

Zebrafish are used in laboratories precisely because they are close enough to humans to be meaningful: roughly 70 percent of human genes have a counterpart in the fish, and young specimens are transparent, so bone development can be tracked under a microscope without any dissection.

What the Gene Analysis Showed

The authors, among them Erika Kague, Beatriz Larraz Prieto, Renata A. Raele, Bianca Ventura Fernandes and Joanna Moss, together with Chrissy L. Hammond, examined which genes in these fish were switched on more strongly and which were suppressed. The disruption showed up in four areas:

• fat processing
• the mTOR pathway, which regulates growth
• phosphate handling
• vitamin A signaling

Each of these four processes has been linked in the literature to abnormal mineral deposits. The paper does not name them as causes, only as places where a drug would have something to act on.

Can the Damage Be Reduced?

In fish, yes, and in three separate ways. The bisphosphonate stopped mineral buildup. Reduced food intake cut down on vertebrae fusing together. Drugs that slow fat metabolism pushed the outcome in the same direction.

The research was led by Dr. Erika Kague of the University of Edinburgh.

“For decades, surgery has been the only real answer for disc disease. By understanding the biology that drives the spine to harden, our research in zebrafish points to several ways to slow that process down.”

Kague added, in a statement from the university, that “for a condition that has affected people for generations, with no treatment even on the horizon, this is incredibly exciting.”

The research was funded by the organization Arthritis UK and the British research body BBSRC. Dr. Caroline Aylott of Arthritis UK said that “for the 9.5 million people across Britain living with back pain, this research brings new hope.”

The real number is far larger than the British one. According to the World Health Organization (WHO), 619 million people worldwide were living with lower back pain in 2020, and the projection for 2050 is 843 million. It is the single leading cause of years lived with disability in the world, and so far there is not a single drug that halts the process.

That is what makes the choice of a bisphosphonate practically important. This class of drugs has been prescribed for decades, its safety profile is well established, and its dosing and administration have long been standardized. If the result holds up, the path from laboratory to patient is shorter than it would be for a molecule that still has to go through a first clinical trial phase.

What This Does Not Prove

The work was done in fish. The zebrafish had a single gene switched off, and what was measured was ligament mineralization and vertebral fusion, which is not the same as an adult human disc under everyday load. No patient has been treated, and no clinical trial has started.

The gene activity analysis shows that fat processing, mTOR, phosphates and vitamin A are associated with the process, not that they cause it. Nor is the finding about reduced food intake a dietary recommendation, since it refers to an experimental regimen for aquarium fish, not to humans.

What the study actually offers is a list of targets and a model on which those targets can be tested quickly. The next step that logically follows is data on people who have already been taking bisphosphonates for years because of osteoporosis: if the mechanism also holds in humans, their spines should look different on scans from those of peers who do not take the drugs. Nobody has published that data yet.