by University of Queensland

Credit: Cell Reports Medicine (2024). DOI: 10.1016/j.xcrm.2024.101849

Queensland researchers have solved the century-old mystery of why patients who suffer severe spinal cord and brain injuries develop debilitating bone growths around joints such as hips and shoulders.

Neurogenic heterotopic ossification (NHO) affects about 20% of patients who suffer spinal cord injuries and can lead to a complete loss of movement in the affected joints as they become encased in bone.

The condition was first fully documented during the First World War thanks to the invention of X-ray scans, which revealed masses of bones growing around the joints of soldiers who had survived traumatic spinal and brain injuries on the battlefield.

Now scientists at Mater Research and The University of Queensland have discovered why the condition occurs—and identified existing drugs that can prevent it.

The 10-year study was led by Dr. Kylie Alexander and Professor Jean-Pierre Levesque and also involved clinicians based at the Raymond-Poincare Hospital in Paris.

“Heterotopic ossification is a serious but common problem among patients who have suffered traumatic spinal and brain injuries,” Dr. Alexander said.

“It is especially likely to affect soldiers who are wounded in action, but most Australian patients with the condition have typically been in a car or motorcycle crash, or sport and workplace accident.

“It is a horrible condition to be afflicted with following a serious injury, with long and delicate surgeries to cut away the bone growth the only available treatment. Sometimes the condition recurs after surgery.”

Prof Levesque said the research team had identified the stress hormone cortisol—which spikes following brain and spinal injuries—as the trigger for neurogenic heterotopic ossification.

“We found that if a cortisol spike happens at the same that a muscle injury occurs, the body’s normal repair program is derailed; instead of repairing the muscle tissue the body grows bone,” Prof Levesque said.

“The good news is that drugs that block cortisol receptors have been around for decades and can effectively prevent ossification if administered soon after spinal and brain injuries occur.

“However, our study also found that cortisol mimetics, which are widely used as strong anti-inflammatory drugs to reduce the neuroinflammation caused by spinal cord injury, have the potential to worsen heterotopic ossification in patients.”

The study “A glucocorticoid spike derails muscle repair to heterotopic ossification after spinal cord injury” was published Dec. 9 in Cell Reports Medicine.

The research team, based at Brisbane’s Translational Research Institute, is now aiming to continue its work by investigating the genetic and cellular mechanisms by which cortisol causes joint ossification.

The study team hopes to initiate clinical trials of a treatment for neurogenic heterotopic ossification in the next two to three years, involving spinal cord units at hospitals in Australia, the U.S. and Europe.

The study results have been welcomed by Queensland NHO sufferer Rohan Sills, 34.

Mr. Sills was working as a carpenter in 2016 when he fell 4 meters through a stair void on a worksite, suffering a major spinal injury which left him a wheelchair-bound T5 paraplegic.

He suffered two-and-a-half years of pain waiting for bone to stop growing around his left hip so it could be removed by surgery at Mater Private Hospital Brisbane.

“Having a spinal injury obviously changes your entire life and NHO is then another challenge to overcome,” he said.

“I was in pain for more than two years and it seriously impacted my lifestyle. Sport is my outlet, but I couldn’t do anything until the bone was removed from my hip.”

Mr. Sills, of Ipswich, can now play wheelchair sports and volunteers in the Spinal Injuries Unit at Brisbane’s Princess Alexandra Hospital.

“This research is massive for people with spinal injuries. I hope that one day it will mean less pain for patients and the chance to rebuild their lives more quickly.”

Spinal Life Australia CEO Mark Townend said the study’s findings were “ground-breaking.”

“This is a significant milestone in understanding and treating a condition that affects countless individuals living with Spinal Cord Injuries and other complex conditions,” he said.

“By identifying the root cause of HO, Mater Research is much closer to developing effective treatments and improving the quality of life for those impacted both here in Australia and globally.

“The research holds immense promise for transforming the lives of people with HO, offering hope for a brighter future.”

More information: Kylie A. Alexander et al, A glucocorticoid spike derails muscle repair to heterotopic ossification after spinal cord injury, Cell Reports Medicine (2024). DOI: 10.1016/j.xcrm.2024.101849

Journal information:Cell Reports Medicine

Provided by the University of Queensland

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