title: Long-term effects of bisphosphonate therapy: perforations, microcracks and mechanical properties.
abstract: 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.
authors.affiliation: Department of Mechanical Engineering, Faculty of Engineering, Imperial College London, London, SW7 2AZ, United Kingdom.|MSk Laboratory, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, London, W6 8PR, United Kingdom.
authors.forename: Shaocheng
authors.initials: S
authors.lastname: Ma
authors.affiliation: MSk Laboratory, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, London, W6 8PR, United Kingdom.
authors.forename: En Lin
authors.initials: EL
authors.lastname: Goh
authors.affiliation: Department of Mechanical Engineering, Faculty of Engineering, Imperial College London, London, SW7 2AZ, United Kingdom.|MSk Laboratory, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, London, W6 8PR, United Kingdom.
authors.forename: Andi
authors.initials: A
authors.lastname: Jin
authors.affiliation: St. Mary's Hospital, North West London Major Trauma Centre, Imperial College, London, W2 1NY, United Kingdom.
authors.forename: Rajarshi
authors.initials: R
authors.lastname: Bhattacharya
authors.affiliation: Department of Mechanical Engineering, Faculty of Engineering, Imperial College London, London, SW7 2AZ, United Kingdom.|MSk Laboratory, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, London, W6 8PR, United Kingdom.
authors.forename: Oliver R
authors.initials: OR
authors.lastname: Boughton
authors.affiliation: MSk Laboratory, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, London, W6 8PR, United Kingdom.
authors.forename: Bhavi
authors.initials: B
authors.lastname: Patel
authors.affiliation: Department of Mechanical Engineering, Faculty of Engineering, University of Moratuwa, Moratuwa, 10400, Sri Lanka.
authors.forename: Angelo
authors.initials: A
authors.lastname: Karunaratne
authors.affiliation: Diamond Light Source Ltd, Harwell Science and Innovation Campus, Didcot, OX11 0DE, United Kingdom.
authors.forename: Nghia T
authors.initials: NT
authors.lastname: Vo
authors.affiliation: Diamond Light Source Ltd, Harwell Science and Innovation Campus, Didcot, OX11 0DE, United Kingdom.
authors.forename: Robert
authors.initials: R
authors.lastname: Atwood
authors.affiliation: MSk Laboratory, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, London, W6 8PR, United Kingdom.
authors.forename: Justin P
authors.initials: JP
authors.lastname: Cobb
authors.affiliation: Department of Mechanical Engineering, Faculty of Engineering, Imperial College London, London, SW7 2AZ, United Kingdom.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Hansen
authors.affiliation: MSk Laboratory, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, London, W6 8PR, United Kingdom.
authors.forename: Richard L
authors.initials: RL
authors.lastname: Abel
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D019386:Alendronate / Q000627:therapeutic use*; D015519:Bone Density / Q000187:drug effects; D050071:Bone Density Conservation Agents / Q000627:therapeutic use*; D016723:Bone Remodeling / Q000187:drug effects; D001842:Bone and Bones / Q000000981:diagnostic imaging* / Q000187:drug effects / Q000293:injuries; D016022:Case-Control Studies; D055119:Elastic Modulus; D005260:Female; D050723:Fractures, Bone / Q000000981:diagnostic imaging* / Q000473:pathology / Q000601:surgery; D006801:Humans; D007090:Image Interpretation, Computer-Assisted; D008297:Male; D008875:Middle Aged; D010024:Osteoporosis / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology; D017356:Synchrotrons; D013718:Tensile Strength; D055114:X-Ray Microtomography
chemical_list: D050071:Bone Density Conservation Agents; D019386:Alendronate