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Osteoporosis, a disease that causes bones to become fragile, affects around 200 million people across the world and contributes to 8.9 million fractures every year. The bisphosphonate (BP) family of drugs is widely used in the treatment for osteoporosis. BP prevents the loss of bone by slowing down the natural renewal process that breaks down old bone. Although BP has been shown to reduce the number of fractures due to osteoporosis, there is increasing evidence that the drug’s long-term effects may not be entirely positive.
Figure 1: Micro-CT images of bone cores with the lowest bone volume in the study for non-fractured, untreated fracture patients and treated fracture patients. (image from Jinn et al. below)
The issue lies in microcracks, thinner than a human hair, which occur in bone as a natural result of wear and tear. In healthy bone, these cracks are naturally repaired. In patients treated with BP, microcracks can accumulate and affect the strength of the bone.
Microcracks are too small to be seen with laboratory imaging techniques, but recent experiments show – for the first time in human bone – that they can be measured with synchrotron light, via a technique called micro-CT.
The scans showed that bone samples from patients taking BP over a prolonged period of time were abnormal. Their samples contained 24% more microcracks than samples from fracture patients who were not taking the drug, and 54% more than were found in healthy bone samples.
After being scanned at Diamond, the bone samples were tested for their mechanical strength. Unsurprisingly, healthy bone was strongest, whereas bone which had fractured was much weaker. However, bone from patients taking BP was weaker still. The data suggest that this reduced strength is due to the higher number of microcracks.
According to Christina Reinhard, who was a beamline scientist on Diamond's Joint Engineering, Environment and Processing beamline (I12) at the time of the research, “a particular challenge of this experiment was to obtain the images from these post-operative samples, without altering those samples by fixing them in resin, freeze-drying them, or similar methods. Any of those methods could introduce the very microcracks that the medical scientists were interested in measuring. At the same time, unfixed samples are sensitive the heating effects from the X-ray beam and tended to produce bubbles or move around which then ruins the image quality. The I12 team and Dr Abel’s team from Imperial College worked closely to develop the protocol for keeping the bone samples in their original state and un-moving during the experiments.”
Patients taking BP shouldn’t worry, however. This is one small study, and indicates the need for further research to help us understand how the drug affects bone. Future experiments at Diamond will tell us more about how and why microcracks form.
Jinn A et al. The effect of long-term bisphosphonate therapy on trabecular bone strength and microcrack density, Bone & Joint Research (2017).
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