Long-term effects of bisphosphonate therapy: perforations, microcracks and mechanical properties of bones

Developers

Shaocheng Ma, En Lin Goh, Ulrich Hansen, Richard L. Abel et al.

Description of the technology

Osteoporosis is one of most important ageing-associated pathology and its adequate therapy contributes to human longevity. Osteoporosis is characterized by trabecular bone loss resulting from increased osteoclast activation and unbalanced coupling between bone resorption and formation, which induces a thinning of trabeculae and trabecular perforations. Bisphosphonates are the frontline therapy for osteoporosis, which act by reducing bone remodeling, and are thought to prevent perforations and maintain microstructure. However, bisphosphonates may oversuppress remodeling resulting in accumulation of microcracks.

This paper aims to investigate the effect of bisphosphonate treatment on bone microstructure and mechanical strength. Assessment of microdamage within the trabecular bone core was performed using synchrotron X-ray microtomography linked to image analysis software. Bone from bisphosphonate-treated fracture patients exhibited fewer perforations but more numerous and larger microcracks than both fracture and non-fracture controls. Furthermore, bisphosphonate-treated bone demonstrated reduced tensile strength and Young’s Modulus. These findings suggest that bisphosphonate therapy is effective at reducing perforations but may also cause microcrack accumulation, leading to a loss of bone microstructural integrity and consequently, reduced mechanical strength of bones.

Practical application

This technology can be used as a method for assessment of microstructural changes in bones of the patients treated with bisphosphonates. For patients on long-term therapy, it can help to predict the critical time-point of microcrack accumulation and optimize bisphosphonate treatment duration. It will allow prescribing bisphosphonates for long enough to increase bone volume and reduce perforations, whilst stopping the medication before a critical accumulation of microcracks.

The technology is applicable both for experimental investigations in the field of ageing mechanism study, particularly, osteoporosis, and (in prospect) for clinical medicine.

Laboratories

• Department of Mechanical Engineering, Faculty of Engineering, Imperial College London, London (UK)
• MSk Laboratory, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, London (UK)
• St. Mary’s Hospital, North West London Major Trauma Centre, Imperial College, London (UK)
• Department of Mechanical Engineering, Faculty of Engineering, University of Moratuwa, Moratuwa (Sri Lanka)
• Diamond Light Source Ltd, Harwell Science and Innovation Campus, Didcot (UK)

Links

Publications

• Ma, S. et al. «Long-term effects of bisphosphonate therapy: perforations, microcracks and mechanical properties." 7 Scientific Reports (2017): 43399.
• Ma, S. et al. «Synchrotron Imaging Assessment of Bone Quality." 1 Clinical Reviews in Bone and Mineral Metabolism (2016): 11.
• Karunaratne, A. et al. «Significant deterioration in nanomechanical quality occurs through incomplete extrafibrillar mineralization in rachitic bone: Evidence from in-situ synchrotron X-ray scattering and backscattered electron imaging." 27 Journal of Bone and Mineral Research (2012): 876–890.