- Micro-cracks inside bone samples from patients treated with bisphosphonate
Early-stage research into bone samples from patients treated with the commonly-prescribed bisphosphonate drugs suggest that people taking bisphosphonates accumulate ‘microcracks’ when compared with healthy aging bone.
Scientists based at Imperial College London have used X-rays to visualise the structure of bone at a high resolution, revealing a large number of tiny cracks in the samples taken from people taking the bisphosphonate family of drugs.
Writing in the Nature journal Scientific Reports, the researchers report that bone samples taken from fracture patients who had been receiving long-term bisphosphonate treatments of more than a year demonstrated significantly more microcracks and a reduced mechanical strength.
“Although this is a very small, early-stage study, the results are quite startling,” explains Dr Richard Abel, lead author of the research, from the Department of Surgery and Cancer at Imperial College London’s Faculty of Medicine. “This research suggests that, in a small number of patients, rather than protection against fractures bisphosphonates may actually make bones more fragile.”
Bisphosphonates are the frontline therapy for osteoporosis, and act by reducing bone remodelling – the lifelong process through which mature bone tissue is removed and new bone tissue is formed. In osteoporosis, the breakdown of older or damaged bone outpaces the rebuilding with new bone, leaving them more prone to damage. 190 million prescriptions for bisphosphonates are issued worldwide every year.
“We now need funding for larger studies to confirm these findings,” adds Dr Abel. “These drugs are not only prescribed to those with osteoporosis, but in combination with some cancer treatments. As our population ages the demand for effective treatments will only increase.”
To investigate this, the researchers analysed samples from fracture patients and compared these to samples taken from healthy cadavers, using one of Diamond’s imaging beamlines, I12. They visualised the microdamage using X-ray micro-CT scans, which offers the unique capability to gain high-resolution images from deep within the bone sample. The microcracks they observed were typically 30-100 µm in length – approximately the same as the width of a human hair.
“These microcracks are like the small cracks that emerge when you repeated flex a plastic ruler,” continues Dr Abel. “They gradually weaken the structure and may make it more prone to breaking.”
“It’s great to see how micro-computed tomography at Diamond has provided an insight into these microcracks,” adds Prof. Laurent Chapon, Director of Physical Sciences at Diamond. “The X-ray beamline used to map these microcracks is mostly employed by scientists to address engineering or environmental problems, so it is good to see that the development of techniques in physical sciences have a direct benefit to medical research as well.”
The next steps will be to broaden the study, says Dr Abel. “There may be a crucial time point between hole development in the bone being prevented by bisphosphonates, and microcracks beginning to form. If we can find this, we may be able to ensure the drugs provide maximum protection against fractures by personalising the duration of treatment.”
People currently taking bisphosphonates prescribed by their doctor should continue to do so, Dr Abel concludes:
“It’s important to reiterate that this is only a small study, which has suggested that we should investigate this area further. People should continue to follow the advice of their GP, and take any drugs that have been prescribed to them.”
Reference: Ma, S. et al. Long-term effects of bisphosphonate therapy: perforations, microcracks and mechanical properties. Sci. Rep. 7, 43399; doi: 10.1038/srep43399 (2017).
The study was funded by the Science and Technology Facilities Council, the Engineering and Physical Sciences Research Council, the Wellcome Trust the Michael Uren Foundation and the Sackler Trust.