title: Cluster analysis of bone microarchitecture from high resolution peripheral quantitative computed tomography demonstrates two separate phenotypes associated with high fracture risk in men and women.
abstract: Osteoporosis is a major healthcare problem which is conventionally assessed by dual energy X-ray absorptiometry (DXA). New technologies such as high resolution peripheral quantitative computed tomography (HRpQCT) also predict fracture risk. HRpQCT measures a number of bone characteristics that may inform specific patterns of bone deficits. We used cluster analysis to define different bone phenotypes and their relationships to fracture prevalence and areal bone mineral density (BMD). 177 men and 159 women, in whom fracture history was determined by self-report and vertebral fracture assessment, underwent HRpQCT of the distal radius and femoral neck DXA. Five clusters were derived with two clusters associated with elevated fracture risk. "Cluster 1" contained 26 women (50.0% fractured) and 30 men (50.0% fractured) with a lower mean cortical thickness and cortical volumetric BMD, and in men only, a mean total and trabecular area more than the sex-specific cohort mean. "Cluster 2" contained 20 women (50.0% fractured) and 14 men (35.7% fractured) with a lower mean trabecular density and trabecular number than the sex-specific cohort mean. Logistic regression showed fracture rates in these clusters to be significantly higher than the lowest fracture risk cluster [5] (p<0.05). Mean femoral neck areal BMD was significantly lower than cluster 5 in women in cluster 1 and 2 (p<0.001 for both), and in men, in cluster 2 (p<0.001) but not 1 (p=0.220). In conclusion, this study demonstrates two distinct high risk clusters in both men and women which may differ in etiology and response to treatment. As cluster 1 in men does not have low areal BMD, these men may not be identified as high risk by conventional DXA alone.
authors.affiliation: MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton General Hospital, Tremona Road, Southampton SO16 6YD, United Kingdom.
authors.forename: M H
authors.initials: MH
authors.lastname: Edwards
authors.affiliation: MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton General Hospital, Tremona Road, Southampton SO16 6YD, United Kingdom.
authors.forename: D E
authors.initials: DE
authors.lastname: Robinson
authors.affiliation: MRC Human Nutrition Research, Elsie Widdowson Laboratory, 120 Fulbourn Road, Cambridge CB1 9NL, United Kingdom.
authors.forename: K A
authors.initials: KA
authors.lastname: Ward
authors.affiliation: NIHR Musculoskeletal Biomedical Research Unit, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford OX3 5UG, United Kingdom.
authors.forename: M K
authors.initials: MK
authors.lastname: Javaid
authors.affiliation: MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton General Hospital, Tremona Road, Southampton SO16 6YD, United Kingdom.
authors.forename: K
authors.initials: K
authors.lastname: Walker-Bone
authors.affiliation: MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton General Hospital, Tremona Road, Southampton SO16 6YD, United Kingdom; NIHR Musculoskeletal Biomedical Research Unit, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford OX3 5UG, United Kingdom; NIHR Nutrition Biomedical Research Centre, University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton General Hospital, Southampton SO16 6YD, United Kingdom. Electronic address: cc@mrc.soton.ac.uk.
authors.forename: C
authors.initials: C
authors.lastname: Cooper
authors.affiliation: MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton General Hospital, Tremona Road, Southampton SO16 6YD, United Kingdom; Victoria University, Wellington, New Zealand.
authors.forename: E M
authors.initials: EM
authors.lastname: Dennison
mesh_terms: D015502:Absorptiometry, Photon; D000368:Aged; D001842:Bone and Bones / Q000000981:diagnostic imaging* / Q000473:pathology*; D016000:Cluster Analysis; D003710:Demography; D005260:Female; D050723:Fractures, Bone / Q000000981:diagnostic imaging* / Q000453:epidemiology / Q000473:pathology*; D006801:Humans; D008019:Life Style; D008297:Male; D016017:Odds Ratio; D010641:Phenotype; D012307:Risk Factors; D014057:Tomography, X-Ray Computed / Q000379:methods*
keywords: Bone QCT; DXA; Epidemiology; Fracture risk assessment; Osteoporosis