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

• Published in: Scientific reports Vol. 7; no. 1; p. 43399
• Main Authors: Ma, Shaocheng, Goh, En Lin, Jin, Andi, Bhattacharya, Rajarshi, Boughton, Oliver R., Patel, Bhavi, Karunaratne, Angelo, Vo, Nghia T., Atwood, Robert, Cobb, Justin P., Hansen, Ulrich, Abel, Richard L.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 06.03.2017; Nature Publishing Group
• Subjects: 631/1647/245/1847; 631/1647/245/2221; 692/308/575; Aged; Aged, 80 and over; Alendronate - therapeutic use; Bone and Bones - diagnostic imaging; Bone and Bones - drug effects; Bone and Bones - injuries; Bone Density - drug effects; Bone Density Conservation Agents - therapeutic use; Bone Remodeling - drug effects; Case-Control Studies; Elastic Modulus; Female; Fractures, Bone - diagnostic imaging; Fractures, Bone - pathology; Fractures, Bone - surgery; Humanities and Social Sciences; Humans; Image Interpretation, Computer-Assisted; Male; Middle Aged; multidisciplinary; Osteoporosis - diagnostic imaging; Osteoporosis - drug therapy; Osteoporosis - pathology; Science; Synchrotrons; Tensile Strength; X-Ray Microtomography
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep43399

Osteoporosis is characterised by trabecular bone loss resulting from increased osteoclast activation and unbalanced coupling between resorption and formation, which induces a thinning of trabeculae and trabecular perforations. Bisphosphonates are the frontline therapy for osteoporosis, which act by reducing bone remodelling, and are thought to prevent perforations and maintain microstructure. However, bisphosphonates may oversuppress remodelling resulting in accumulation of microcracks. This paper aims to investigate the effect of bisphosphonate treatment on microstructure and mechanical strength. Assessment of microdamage within the trabecular bone core was performed using synchrotron X-ray micro-CT 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 microstructural integrity and consequently, reduced mechanical strength.