Breakthrough set to enable development of new therapies to reverse bone loss
In a global breakthrough published in Nature Genetics, researchers have successfully mapped the cells and genes that regulate bone formation and loss at an unprecedented scale and discovered the critical role that blood vessel cells play in bone health.
By combining genomic sequencing with data from half a million individuals, the research team identified hundreds of previously unknown genes that govern bone health and revealed cells surrounding blood vessels as one of the drivers of bone repair — a role that has been underappreciated until now.
Led by Associate Professor John Kemp from Mater Research and The University of Queensland, Professor Peter Croucher and Dr Ryan Chai from the Garvan Institute of Medical Research and Professor Graham Williams and Professor Duncan Bassett from Imperial College London, the team’s findings fundamentally enhance our understanding of skeletal disease.
It is hoped the discovery will enable the development of new therapies to rebuild lost bone – offering hope to the half a billion people with osteoporosis worldwide, including almost half of all individuals over 50 living with rare and common skeletal conditions such as osteoporosis, osteoarthritis and osteogenesis imperfecta, as well as those with rare bone disorders and cancers that spread to bone.
“Most people don’t realise that bones are constantly changing – the human body replaces its skeleton every 10 years or so,” Professor Croucher said.
“This is a hugely important process, but until now we’ve had a very limited understanding of the cells and mechanisms that control this turnover of bone.
“Most of the drugs now available focus only on halting bone disease, rather than rebuilding lost bone, which is really important for reversing damage.”
The most detailed map of cells and genes that regulate bone health
The team used state-of-the-art single-cell RNA sequencing to measure which genes are switched on within individual cells found in bone, focusing on the interface between the hard bone and bone marrow which is the key site for the formation and breakdown of bone.
Dr Chai said the team’s extensive analysis found 34 different groups of cells and defined the genes that are active in each of these cell types.
“To our surprise, more than half of the genes identified have never before been shown to play a role in maintaining bone health, which is a significant finding,” Dr Chai added.
Surprising new role for blood vessel cells
The team used its map to identify cells involved in rare and common skeletal diseases, including osteogenesis imperfecta and osteoporosis. For the latter, the team analysed the UK Biobank, one of the world’s biggest and most comprehensive collections of biological samples.
Associate Professor Kemp said by analysing genetic and bone density data from half a million people participating in the UK Biobank, the team was able to pinpoint exactly which cells drive skeletal disease.
“These include cells known to regulate bone formation and bone loss, as well as blood vessel cells that, until now, have had underappreciated roles in bone health,” Associate Professor Kemp added.
The team validated the function of the newly identified genes in model systems confirming their critical role in skeletal biology.
Professor Duncan Bassett at Imperial College London said that by demonstrating the function of these specific candidate genes, we have gained a better understanding of how bone diseases occur at a cellular and molecular level.
“This means we have discovered potential new targets for future treatments".
Resource to accelerate the development of new therapies
Professor Croucher said the research uncovered new therapeutic opportunities against not only bone disease, but also cancer.
“Bone is the main hiding place for dormant cancer cells and a common site of relapse, so identifying the cells and genes that drive bone turnover also opens new opportunities to prevent cancer metastasis,” he said.
The team is now further investigating the roles of newly discovered bone-regulating cells and genes in the hope of developing new medicines against these targets. Its ground-breaking data has been made accessible to medical researchers worldwide through an open access platform.
“We hope that sharing this knowledge can speed up development of new therapies that prevent diseases like osteoporosis and reverse the damage caused by them,” Dr Kemp said.
New hope for patients living with weakened bones
For patients, the research offers hope for how the disease might be managed in the future.
Brisbane woman Louise Gillard, 68, has lived an exceptionally active life, beginning her career as a professional ballerina with the Scottish Ballet before moving to Australia in 1987 to dance, going on to lead Ballet Theatre of Queensland as Artistic Director and Choreographer from 1990
After retiring from ballet, she continued to be active, working on the shopfloor of a reuse centre.
The first signs that her bones weren’t as strong as everyone else’s appeared early in childhood.
“My baby teeth were worn down before they even fell out, and they chipped very easily,” Mrs Gillard said.
“A dentist in Glasgow suspected something wasn’t right.”
In 2017, she developed severe back pain and a wedge fracture that led to a formal diagnosis of osteogenesis imperfecta, a rare genetic disorder that weakens both bone and dental strength.
Despite decades of elite physical fitness, Mrs Gillard was stunned by the extent of her bone loss.
“When I learned how severe my bone loss was for my age, I couldn’t believe it. Inside, my bones looked like they belonged to someone decades older,” she said.
“I was devastated. It felt like my whole structure was crumbling, and there was nothing I could do to reverse it.”
Specialist care, including bone‑preserving infusions, has since helped stabilise her condition, but the emotional burden of living with fragile bones remains significant.
“Knowing the condition wasn’t reversible was incredibly hard. It really felt like I’d been dealt a bad hand.”
Today, Mrs Gillard maintains her strength through regular walking, light weights and credits her lifelong physical activity with helping protect her bones. But she says the chance for a therapy that could genuinely rebuild bone would be transformative.
“The prospect of new therapies that reverse bone deterioration is absolutely amazing,” she said.
“If researchers can find a way to help people like me grow stronger bone again, it would be incredible. It would give people renewed hope.
“So many older people are in good health except for their bone fragility. A treatment that rebuilds bone could completely change that.”
