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

DOI: 10.1302/2046-3758.610.BJR-2016-0321.R1 DOI Help

Authors: A. Jin (Imperial College London) , J. Cobb (Imperial College London) , U. Hansen (Imperial College London) , R. Bhattacharya (Imperial College London) , C. Reinhard (Diamond Light Source) , N. Vo (Diamond Light Source) , R. Atwood (Diamond Light Source) , J. Li (Imperial College London) , A. Karunaratne (Imperial College London) , C. Wiles (Imperial College London) , R. Abel (Imperial College London)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Bone And Joint Research , VOL 6 , PAGES 602 - 609

State: Published (Approved)
Published: October 2017
Diamond Proposal Number(s): 9811 , 852

Open Access Open Access

Abstract: Objectives Bisphosphonates (BP) are the first-line treatment for preventing fragility fractures. However, concern regarding their efficacy is growing because bisphosphonate is associated with over-suppression of remodelling and accumulation of microcracks. While dual-energy X-ray absorptiometry (DXA) 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), and correlate data 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 with naïve fractured (n = 14) and non-fractured controls (n = 6). Trabecular cores were synchrotron scanned and micro-CT scanned for microstructural analysis, including quantification of bone volume fraction, microarchitecture and microcracks. The specimens were then mechanically tested in compression. Results BP bone was 28% lower in strength than untreated hip fracture bone, and 48% lower in strength than non-fractured control bone (4.6 MPa vs 6.4 MPa vs 8.9 MPa). BP-treated bone had 24% more microcracks than naïve fractured bone and 51% more than non-fractured control (8.12/cm2 vs 6.55/cm2 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. Conclusion BP therapy had no detectable mechanical benefit in the specimens examined. Instead, its use was associated with substantially reduced bone strength. This low strength may be 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 significant.

Subject Areas: Biology and Bio-materials, Medicine

Instruments: I12-JEEP: Joint Engineering, Environmental and Processing