The effect of long term bisphosphonate therapy on trabecular bone strength and microcrack density

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Title: The effect of long term bisphosphonate therapy on trabecular bone strength and microcrack density
Author(s): Jin, A
Cobb, JP
Hansen, U
Bhattacharya, R
Reinhard, C
Vo, N
Atwood, R
Li, J
Abel, RL
Item Type: Journal Article
Abstract: Objectives Bisphosphonates (BP) are the first-line treatment for preventing fragility fractures. However, concern regarding the efficacy is growing because bisphosphonate is associated with over-suppression of remodelling and accumulation of microcracks. While DEXA scanning may show a gain in bone density the impact of this class of drug on mechanical properties remains unclear. We therefore sought to quantify the mechanical strength of bone treated with BP (oral alendronate for this study), and correlate this with the microarchitecture and density of microcracks in comparison with untreated controls. Methods Trabecular bone from hip-fracture patients treated with BP (n=10) was compared to naïve fractured (n=14) and non-fractured controls (n=6). Trabecular cores were synchrotron and micro-CT scanned for microstructural analysis including quantification of bone volume fraction, micro-architecture and microcracks, then mechanically tested in compression. Results BP bone was 28% lower in strength than untreated hip-fracture bone and 48% lower in strength than and non-fracture control bone (4.6 vs 6.4 vs 8.9 MPa). BP treated bone had 24% more microcracks than naïve fractured bone and 51% more than non-fractured control (8.12 vs 6.55 vs 5.25 /cm2). BP and naïve fracture bone exhibited similar trabecular microarchitecture, with significantly lower bone volume fraction and connectivity than non-fractured controls. Conclusions BP therapy had no detectable mechanical benefit. Instead its use was associated with substantially reduced bone strength. This low strength was probably due to the greater accumulation of microcracks and a lack of any discernible improvement in bone volume or microarchitecture. This preliminary study suggests that the clinical impact of BP induced microcrack accumulation may be substantial and long term.
Publication Date: 24-Oct-2017
Date of Acceptance: 18-Apr-2017
URI: http://hdl.handle.net/10044/1/48230
DOI: https://dx.doi.org/10.1302/2046-3758.610.BJR-2016-0321.R1
ISSN: 2046-3758
Publisher: British Editorial Society of Bone and Joint Surgery
Start Page: 602
End Page: 609
Journal / Book Title: Bone & Joint Research
Volume: 6
Issue: 10
Copyright Statement: © 2017 Jin et al. This is an open-access article distributed under the terms of the Creative Commons Attributions licence (CC-BY-NC), which permits unrestricted use, distribution, and reproduction in any medium, but not for commercial gain, provided the original author and source are credited.
Keywords: Science & Technology
Life Sciences & Biomedicine
Cell & Tissue Engineering
Orthopedics
Cell Biology
Ageing
Biomechanics
Osteoporosis
Antiresorptives
MICRODAMAGE ACCUMULATION
BIOMECHANICAL PROPERTIES
SYNCHROTRON-RADIATION
VERTEBRAL FRACTURES
WOMEN
MICROARCHITECTURE
ALENDRONATE
RISK
TURNOVER
MICROTOMOGRAPHY
Publication Status: Published
Appears in Collections:Faculty of Engineering
Mechanical Engineering
Division of Surgery
Faculty of Medicine



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