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Major trial shows increasing bone density fails to cut fracture risk in brittle bone disease

May 15, 2026

3 min


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An international clinical trial involving Aston University researchers has challenged long held assumptions about how brittle bone disease is treated in adults, after finding that substantially increasing bone density did not reduce the risk of fractures.


The study, published in the Journal of the American Medical Association (JAMA), examined whether a two stage treatment using the bone building drug teriparatide followed by the bone preserving drug zoledronic acid could reduce fractures in adults with osteogenesis imperfecta, often referred to as brittle bone disease, a rare genetic condition that causes bones to break easily throughout life.


Researchers followed 349 adults treated at 27 specialist centres across the UK and Europe. While the treatment led to clear increases in bone density in the spine and hip, fracture rates were no lower than among patients receiving standard care, suggesting that bone quality may matter more than bone density alone in preventing fractures in people with the condition.


The findings underline a key distinction between brittle bone disease and more common bone conditions such as osteoporosis, where increasing bone density is known to reduce fracture risk.

In osteogenesis imperfecta, the study suggests that bones can become denser without becoming less likely to break, indicating that the underlying quality and structure of bone tissue may play a greater role in fracture risk than density alone.


Dr Zaki Hassan Smith, an endocrinologist at Aston Medical School who contributed to the research, said:


“This study shows that in osteogenesis imperfecta, simply increasing bone density doesn’t necessarily translate into fewer fractures. That’s important, because it tells us that the disease is more complex than what we see on a scan. The findings help shift the focus towards understanding bone quality and how bones behave in real life, which is essential if we are to develop more effective treatments that genuinely reduce harm for patients.”


Osteogenesis imperfecta is a genetic condition that affects collagen, leaving bones fragile and prone to fracture throughout life. There is currently no licensed treatment specifically approved to prevent fractures in adults with the condition, and patients often experience repeated fractures, chronic pain and long term disability.


The trial tested a sequential treatment strategy commonly used in osteoporosis, where a bone building drug is followed by a treatment designed to preserve gains in bone strength. Although this approach successfully increased bone density in people with osteogenesis imperfecta, it did not reduce fracture rates, suggesting that treatment strategies effective in osteoporosis may not directly translate to rare bone diseases.


Researchers did observe improvements in some quality of life measures among participants receiving the treatment, including reduced pain interference and improved mobility. However, fracture prevention remained unchanged, reinforcing the need for new approaches that target the fundamental properties of bone in osteogenesis imperfecta rather than density alone.


The study was led by the University of Edinburgh and funded by the Medical Research Council and the National Institute for Health and Care Research. Aston University contributed clinical and academic expertise through Aston Medical School as part of the large international collaboration, which involved specialist centres across the UK and Europe.


The study was led by the University of Edinburgh, with Aston University contributing clinical and academic expertise as part of a wider international collaboration involving multiple specialist centres across the UK and Europe. The research was funded by the Medical Research Council and the National Institute for Health and Care Research.


Researchers say the findings provide important guidance for future research, helping to steer efforts towards treatments that focus on bone quality, strength and resilience in everyday life. They also highlight the value of large scale clinical trials in rare diseases, where learning what does not reduce harm is an essential step towards better care.


The paper, Teriparatide Plus Zoledronic Acid for Osteogenesis Imperfecta, is published in JAMA.


https://doi.org/10.1001/jama.2026.6889



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