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Level and change in bone microarchitectural parameters and their relationship with previous fracture and established bone mineral density loci

Level and change in bone microarchitectural parameters and their relationship with previous fracture and established bone mineral density loci
Level and change in bone microarchitectural parameters and their relationship with previous fracture and established bone mineral density loci
Background: osteoporosis is characterised by a reduction of bone mineral density (BMD) and predisposition to fracture. Bone microarchitecture, measured by high resolution peripheral quantitative computed tomography (HR-pQCT), has been related to fragility fractures and BMD and has been the subject of large-scale genome-wide analysis. We investigated whether fracture was related to baseline values and longitudinal changes in bone microarchitecture and whether bone microarchitecture was associated with established BMD loci. Methods: 115 males and 99 females (aged 72–81 at baseline) from the Hertfordshire Cohort Study (HCS) were analysed. Fracture history was determined in 2011–2012 by self-report and vertebral fracture assessment. Participants underwent HR-pQCT scans of the distal radius and tibia in 2011–2012 and 2017. Previous fracture in relation to baseline values and changes in tibial HR-pQCT parameters was examined using sex-adjusted logistic regression with and without adjustment for age, sociodemographic, lifestyle and clinical characteristics; baseline values and changes in parameters associated with previous fracture were then examined in relation to four established BMD loci after adjustment for sex and age. Results: previous fracture was related to: higher trabecular area (fully-adjusted odds ratio [95% CI] per SD greater baseline value: 2.18 [1.27,3.73], p = 0.005); lower total volumetric BMD (0.53 [0.34,0.84], p = 0.007), cortical area (0.53 [0.30,0.95], p = 0.032), cortical BMD (0.56 [0.36,0.88], p = 0.011) and cortical thickness (0.45 [0.27,0.77], p = 0.004); and greater declines in trabecular BMD (p = 0.001). Associations were robust in sex- and fully-adjusted analysis. Relationships between BMD loci and these HR-pQCT parameters were weak: rs3801387 (WNT16) was related to decline in trabecular BMD (p = 0.011) but no other associations were significant (p > 0.05). Conclusion: baseline values of HR-pQCT parameters and greater decline in trabecular BMD were associated with fracture. Change in trabecular BMD was associated with WNT16 which has been demonstrated to influence bone health in murine models and human genome-wide association studies (GWAS).
Epidemiology, Fracture, Loci, Osteoporosis, Quantitative computed tomography
8756-3282
Fuggle, Nicholas
9ab0c81a-ac67-41c4-8860-23e0fdb1a900
Westbury, Leo
5ed45df3-3df7-4bf9-bbad-07b63cd4b281
Bevilacqua, Gregorio
e93e3b18-7d1e-4da5-9fcd-e6b4637e1c2e
Titcombe, Philip
a84c9fad-0580-42f9-8bb6-db0fe20435aa
Breasail, Micheal O.
91913ba1-a694-4365-80f0-dc253cc025c2
Harvey, Nicholas
ce487fb4-d360-4aac-9d17-9466d6cba145
Dennison, Elaine
ee647287-edb4-4392-8361-e59fd505b1d1
Cooper, Cyrus
e05f5612-b493-4273-9b71-9e0ce32bdad6
Ward, Kate
39bd4db1-c948-4e32-930e-7bec8deb54c7
Fuggle, Nicholas
9ab0c81a-ac67-41c4-8860-23e0fdb1a900
Westbury, Leo
5ed45df3-3df7-4bf9-bbad-07b63cd4b281
Bevilacqua, Gregorio
e93e3b18-7d1e-4da5-9fcd-e6b4637e1c2e
Titcombe, Philip
a84c9fad-0580-42f9-8bb6-db0fe20435aa
Breasail, Micheal O.
91913ba1-a694-4365-80f0-dc253cc025c2
Harvey, Nicholas
ce487fb4-d360-4aac-9d17-9466d6cba145
Dennison, Elaine
ee647287-edb4-4392-8361-e59fd505b1d1
Cooper, Cyrus
e05f5612-b493-4273-9b71-9e0ce32bdad6
Ward, Kate
39bd4db1-c948-4e32-930e-7bec8deb54c7

Fuggle, Nicholas, Westbury, Leo, Bevilacqua, Gregorio, Titcombe, Philip, Breasail, Micheal O., Harvey, Nicholas, Dennison, Elaine, Cooper, Cyrus and Ward, Kate (2021) Level and change in bone microarchitectural parameters and their relationship with previous fracture and established bone mineral density loci. Bone, 147, [115937]. (doi:10.1016/j.bone.2021.115937).

Record type: Article

Abstract

Background: osteoporosis is characterised by a reduction of bone mineral density (BMD) and predisposition to fracture. Bone microarchitecture, measured by high resolution peripheral quantitative computed tomography (HR-pQCT), has been related to fragility fractures and BMD and has been the subject of large-scale genome-wide analysis. We investigated whether fracture was related to baseline values and longitudinal changes in bone microarchitecture and whether bone microarchitecture was associated with established BMD loci. Methods: 115 males and 99 females (aged 72–81 at baseline) from the Hertfordshire Cohort Study (HCS) were analysed. Fracture history was determined in 2011–2012 by self-report and vertebral fracture assessment. Participants underwent HR-pQCT scans of the distal radius and tibia in 2011–2012 and 2017. Previous fracture in relation to baseline values and changes in tibial HR-pQCT parameters was examined using sex-adjusted logistic regression with and without adjustment for age, sociodemographic, lifestyle and clinical characteristics; baseline values and changes in parameters associated with previous fracture were then examined in relation to four established BMD loci after adjustment for sex and age. Results: previous fracture was related to: higher trabecular area (fully-adjusted odds ratio [95% CI] per SD greater baseline value: 2.18 [1.27,3.73], p = 0.005); lower total volumetric BMD (0.53 [0.34,0.84], p = 0.007), cortical area (0.53 [0.30,0.95], p = 0.032), cortical BMD (0.56 [0.36,0.88], p = 0.011) and cortical thickness (0.45 [0.27,0.77], p = 0.004); and greater declines in trabecular BMD (p = 0.001). Associations were robust in sex- and fully-adjusted analysis. Relationships between BMD loci and these HR-pQCT parameters were weak: rs3801387 (WNT16) was related to decline in trabecular BMD (p = 0.011) but no other associations were significant (p > 0.05). Conclusion: baseline values of HR-pQCT parameters and greater decline in trabecular BMD were associated with fracture. Change in trabecular BMD was associated with WNT16 which has been demonstrated to influence bone health in murine models and human genome-wide association studies (GWAS).

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HRpQCT level and change paper 21_3_1 (clean)_ - Accepted Manuscript
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Accepted/In Press date: 18 March 2021
e-pub ahead of print date: 22 March 2021
Published date: 1 June 2021
Keywords: Epidemiology, Fracture, Loci, Osteoporosis, Quantitative computed tomography

Identifiers

Local EPrints ID: 448655
URI: http://eprints.soton.ac.uk/id/eprint/448655
ISSN: 8756-3282
PURE UUID: 47ff5929-357b-42f8-9b1c-dcf1955f5426
ORCID for Gregorio Bevilacqua: ORCID iD orcid.org/0000-0001-7819-1482
ORCID for Philip Titcombe: ORCID iD orcid.org/0000-0002-7797-8571
ORCID for Nicholas Harvey: ORCID iD orcid.org/0000-0002-8194-2512
ORCID for Elaine Dennison: ORCID iD orcid.org/0000-0002-3048-4961
ORCID for Cyrus Cooper: ORCID iD orcid.org/0000-0003-3510-0709
ORCID for Kate Ward: ORCID iD orcid.org/0000-0001-7034-6750

Catalogue record

Date deposited: 29 Apr 2021 16:30
Last modified: 26 Nov 2021 03:05

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Contributors

Author: Nicholas Fuggle
Author: Leo Westbury
Author: Gregorio Bevilacqua ORCID iD
Author: Philip Titcombe ORCID iD
Author: Micheal O. Breasail
Author: Nicholas Harvey ORCID iD
Author: Elaine Dennison ORCID iD
Author: Cyrus Cooper ORCID iD
Author: Kate Ward ORCID iD

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