Osteoporosis Drugs 'Simply Do Not Work' for Brittle Bone Disease, Major Trial Finds

A landmark eight-year study has found that drugs commonly used to increase bone density do not reduce fracture rates in adults with osteogenesis imperfecta (OI), a finding that experts say should "fundamentally change clinical practice."

Key Findings

• The TOPaZ trial followed 350 adults with OI over eight years (May 2017 – March 2025)
• Half received drug treatments to increase bone density; the other half received standard care
• Bone density significantly increased in the treatment group, but fracture rates were nearly identical
• 37% (treated) vs 36% (standard care) experienced fractures
• There was no reduction in total new fractures or spine fractures

Background

OI — commonly known as brittle bone disease — is caused by a defect in collagen production, leading to fragile bones. It affects approximately 1 in 15,000 people.

For decades, treatment has focused on drugs that increase bone density, despite limited evidence that this actually reduces fractures. The TOPaZ trial now provides the clearest picture yet of their ineffectiveness for this specific condition.

Expert Reaction

Professor Stuart Ralston (University of Edinburgh) stated that the results "will fundamentally change clinical practice" and that these drugs "simply do not work" for preventing fractures. He called for urgent research into drugs targeting bone collagen defects instead.

Patricia Osborne (CEO, Brittle Bone Society) said the trial provides clear evidence to guide treatment decisions and highlights the critical importance of OI-specific research.

Publication

The study — supported by the Brittle Bone Society and funded by the Medical Research Council and NIHR — is published in the Journal of the American Medical Association (JAMA). The research team included scientists from 27 hospitals across the UK and Europe.