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Telomere length and risk of incident fractures and arthroplasty: findings from the UK Biobank.

Telomere length and risk of incident fractures and arthroplasty: findings from the UK Biobank.
Telomere length and risk of incident fractures and arthroplasty: findings from the UK Biobank.
We investigated independent associations between telomere length and risk of fracture and arthroplasty in UK Biobank participants. Leucocyte telomere length (LTL) was measured in baseline samples using a validated PCR method. We used, in men and women separately, Cox proportional hazards models to calculate the hazard ratio for incident fracture (any, osteoporotic) or arthroplasty (hip or knee) over 1,186,410 person-years of follow-up. Covariates included age, white cell count, ethnicity, smoking, alcohol, physical activity and menopause (women). In further analyses we adjusted for either estimated bone mineral density from heel quantitative ultrasound, handgrip strength, gait speed, total fat mass (bioimpedance) or blood biomarkers, all measured at baseline (2006-2010). We studied 59,500 women and 51,895 men, mean(SD) age 56.4(8.0) and 57.0(8.3) years respectively. During follow-up there were 5,619 fractures; 5,285 hip and 4,261 knee arthroplasties. In confounder-adjusted models, longer LTL was associated with reduced risk of incident knee arthroplasty in both men [hazard ratio/SD (95%CI): 0.93 (0.88,0.97)] and women [0.92 (0.88,0.96)] and hip arthroplasty in men [0.91 (0.87,0.95)] but not women [0.98 (0.94,1.01)]. Longer LTL was weakly associated with reduced risk of any incident fracture in women [hazard ratio/SD (95% CI): 0.96 (0.93,1.00)] with less evidence in men [0.98 (0.93,1.02)]. Associations with incident outcomes were not materially altered by adjustment for heel estimated bone mineral density, grip strength, gait speed, fat mass or blood biomarker measures. In this, the largest study to date, longer LTL was associated with lower risk of incident knee or hip arthroplasty, but only weakly associated with lower risk of fracture. The relative risks were low at a population level, but our findings suggest that common factors acting on the myeloid and musculoskeleletal systems might influence later life musculoskeletal outcomes.
AGING, EPIDEMIOLOGY, LEUCOCYTE TELOMERE LENGTH, OSTEOARTHRITIS, OSTEOPOROSIS
0884-0431
1997-2004
Curtis, Elizabeth
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Codd, Veryan
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Nelson, Christopher
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D'angelo, Stefania
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Wang, Qingning
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Allara, Elias
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Kaptoge, Stephen K.
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Matthews, Paul M.
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Tobias, Jonathan H.
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Danesh, John
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Cooper, Cyrus
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Samani, Nilesh J.
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Harvey, Nicholas
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Curtis, Elizabeth
12aba0c3-1e9e-49ef-a7e9-3247e649cdd6
Codd, Veryan
18ed4108-1eb4-4702-bff1-468efae23aae
Nelson, Christopher
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D'angelo, Stefania
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Wang, Qingning
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Allara, Elias
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Kaptoge, Stephen K.
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Matthews, Paul M.
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Tobias, Jonathan H.
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Danesh, John
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Cooper, Cyrus
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Samani, Nilesh J.
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Harvey, Nicholas
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Curtis, Elizabeth, Codd, Veryan, Nelson, Christopher, D'angelo, Stefania, Wang, Qingning, Allara, Elias, Kaptoge, Stephen K., Matthews, Paul M., Tobias, Jonathan H., Danesh, John, Cooper, Cyrus, Samani, Nilesh J. and Harvey, Nicholas (2022) Telomere length and risk of incident fractures and arthroplasty: findings from the UK Biobank. Journal of Bone and Mineral Research, 37 (10), 1997-2004. (doi:10.1002/jbmr.4664).

Record type: Article

Abstract

We investigated independent associations between telomere length and risk of fracture and arthroplasty in UK Biobank participants. Leucocyte telomere length (LTL) was measured in baseline samples using a validated PCR method. We used, in men and women separately, Cox proportional hazards models to calculate the hazard ratio for incident fracture (any, osteoporotic) or arthroplasty (hip or knee) over 1,186,410 person-years of follow-up. Covariates included age, white cell count, ethnicity, smoking, alcohol, physical activity and menopause (women). In further analyses we adjusted for either estimated bone mineral density from heel quantitative ultrasound, handgrip strength, gait speed, total fat mass (bioimpedance) or blood biomarkers, all measured at baseline (2006-2010). We studied 59,500 women and 51,895 men, mean(SD) age 56.4(8.0) and 57.0(8.3) years respectively. During follow-up there were 5,619 fractures; 5,285 hip and 4,261 knee arthroplasties. In confounder-adjusted models, longer LTL was associated with reduced risk of incident knee arthroplasty in both men [hazard ratio/SD (95%CI): 0.93 (0.88,0.97)] and women [0.92 (0.88,0.96)] and hip arthroplasty in men [0.91 (0.87,0.95)] but not women [0.98 (0.94,1.01)]. Longer LTL was weakly associated with reduced risk of any incident fracture in women [hazard ratio/SD (95% CI): 0.96 (0.93,1.00)] with less evidence in men [0.98 (0.93,1.02)]. Associations with incident outcomes were not materially altered by adjustment for heel estimated bone mineral density, grip strength, gait speed, fat mass or blood biomarker measures. In this, the largest study to date, longer LTL was associated with lower risk of incident knee or hip arthroplasty, but only weakly associated with lower risk of fracture. The relative risks were low at a population level, but our findings suggest that common factors acting on the myeloid and musculoskeleletal systems might influence later life musculoskeletal outcomes.

Text
J of Bone Mineral Res - 2022 - Curtis - Telomere length and risk of incident fracture and arthroplasty findings from UK - Accepted Manuscript
Restricted to Repository staff only until 25 July 2023.
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Accepted/In Press date: 20 July 2022
Published date: 25 July 2022
Keywords: AGING, EPIDEMIOLOGY, LEUCOCYTE TELOMERE LENGTH, OSTEOARTHRITIS, OSTEOPOROSIS

Identifiers

Local EPrints ID: 468932
URI: http://eprints.soton.ac.uk/id/eprint/468932
ISSN: 0884-0431
PURE UUID: 0491faa8-9041-46fe-8578-38f2f9b53afd
ORCID for Elizabeth Curtis: ORCID iD orcid.org/0000-0002-5147-0550
ORCID for Stefania D'angelo: ORCID iD orcid.org/0000-0002-7267-1837
ORCID for Cyrus Cooper: ORCID iD orcid.org/0000-0003-3510-0709
ORCID for Nicholas Harvey: ORCID iD orcid.org/0000-0002-8194-2512

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Date deposited: 01 Sep 2022 16:56
Last modified: 17 Nov 2022 02:46

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Contributors

Author: Veryan Codd
Author: Christopher Nelson
Author: Stefania D'angelo ORCID iD
Author: Qingning Wang
Author: Elias Allara
Author: Stephen K. Kaptoge
Author: Paul M. Matthews
Author: Jonathan H. Tobias
Author: John Danesh
Author: Cyrus Cooper ORCID iD
Author: Nilesh J. Samani
Author: Nicholas Harvey ORCID iD

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