Cluster analysis of finite element analysis and bone microarchitectural parameters identifies phenotypes with high fracture risk

Westbury, Leo D.; Shere, Clare; Edwards, Mark H.; Cooper, Cyrus; Dennison, Elaine M.; Ward, Kate A.

Affiliations

¹MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton, UK

²Queen Alexandra Hospital, Portsmouth, UK

³NIHR Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton, UK

⁴NIHR Oxford Biomedical Research Centre, University of Oxford, Oxford, UK

⁵Victoria University of Wellington, Wellington, New Zealand

⁶MRC Nutrition and Bone Health Research Group, Cambridge, UK

Abstract and keywords

High-resolution peripheral quantitative computed tomography (HRpQCT) is increasingly used for exploring associations between bone microarchitectural and finite element analysis (FEA) parameters and fracture. We hypothesised that combining bone microarchitectural parameters, geometry, BMD and FEA estimates of bone strength from HRpQCT may improve discrimination of fragility fractures. The analysis sample comprised of 359 participants (aged 72–81 years) from the Hertfordshire Cohort Study. Fracture history was determined by self-report and vertebral fracture assessment. Participants underwent HRpQCT scans of the distal radius and DXA scans of the proximal femur and lateral spine. Poisson regression with robust variance estimation was used to derive relative risks for the relationship between individual bone microarchitectural and FEA parameters and previous fracture. Cluster analysis of these parameters was then performed to identify phenotypes associated with fracture prevalence. Receiver operating characteristic analysis suggested that bone microarchitectural parameters improved fracture discrimination compared to aBMD alone, whereas further inclusion of FEA parameters resulted in minimal improvements. Cluster analysis (k-means) identified four clusters. The first had lower Young modulus, cortical thickness, cortical volumetric density and Von Mises stresses compared to the wider sample; fracture rates were only significantly greater among women (relative risk [95%CI] compared to lowest risk cluster: 2.55 [1.28, 5.07], p = 0.008). The second cluster in women had greater trabecular separation, lower trabecular volumetric density and lower trabecular load with an increase in fracture rate compared to lowest risk cluster (1.93 [0.98, 3.78], p = 0.057). These findings may help inform intervention strategies for the prevention and management of osteoporosis.

Keywords: Quantitative computed tomography; DXA; Epidemiology; Fracture; Osteoporosis; Finite element analysis

Links

DOI: 10.1007/s00223-019-00564-7

PubMed: 31187198

WoS: 000481425800003

History

Received: 2019-03-12

Accepted: 2019-05-10

Online: 2019-06-11

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Cited By (1)

Year	Entry
2022	Bolger MW, Romanowicz GE, Bigelow EMR, Ward FS, Ciarelli A, Jepsen KJ, Kohn DH. Divergent mechanical properties of older human male femora reveal unique combinations of morphological and compositional traits contributing to low strength. Bone. October 2022;163:116481.