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Predictive value of DXA appendicular lean mass for incident fractures, falls and mortality, independent of prior falls, FRAX and BMD: Findings from the Women’s Health Initiative (WHI)

Predictive value of DXA appendicular lean mass for incident fractures, falls and mortality, independent of prior falls, FRAX and BMD: Findings from the Women’s Health Initiative (WHI)
Predictive value of DXA appendicular lean mass for incident fractures, falls and mortality, independent of prior falls, FRAX and BMD: Findings from the Women’s Health Initiative (WHI)
In the Women's Health Initiative (WHI), we investigated associations between baseline dual‐energy X‐ray absorptiometry (DXA) appendicular lean mass (ALM) and risk of incident fractures, falls, and mortality (separately for each outcome) among older postmenopausal women, accounting for bone mineral density (BMD), prior falls, and Fracture Risk Assessment Tool (FRAX®) probability. The WHI is a prospective study of postmenopausal women undertaken at 40 US sites. We used an extension of Poisson regression to investigate the relationship between baseline ALM (corrected for height2) and incident fracture outcomes, presented here for major osteoporotic fracture (MOF: hip, clinical vertebral, forearm, or proximal humerus), falls, and death. Associations were adjusted for age, time since baseline and randomization group, or additionally for femoral neck (FN) BMD, prior falls, or FRAX probability (MOF without BMD) and are reported as gradient of risk (GR: hazard ratio for first incident fracture per SD increment) in ALM/height2 (GR). Data were available for 11,187 women (mean [SD] age 63.3 [7.4] years). In the base models (adjusted for age, follow‐up time, and randomization group), greater ALM/height2 was associated with lower risk of incident MOF (GR = 0.88; 95% confidence interval [CI] 0.83–0.94). The association was independent of prior falls but was attenuated by FRAX probability. Adjustment for FN BMD T‐score led to attenuation and inversion of the risk relationship (GR = 1.06; 95% CI 0.98–1.14). There were no associations between ALM/height2 and incident falls. However, there was a 7% to 15% increase in risk of death during follow‐up for each SD greater ALM/height2, depending on specific adjustment. In WHI, and consistent with our findings in older men (Osteoporotic Fractures in Men [MrOS] study cohorts), the predictive value of DXA‐ALM for future clinical fracture is attenuated (and potentially inverted) after adjustment for femoral neck BMD T‐score. However, intriguing positive, but modest, associations between ALM/height2 and mortality remain robust. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).
APPENDICULAR LEAN MASS, BMD, DXA, FRACTURE, FRAX, OSTEOPOROSIS: EPIDEMIOLOGY
0884-0431
654-661
Harvey, Nicholas
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Kanis, John A.
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Liu, Enwu
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Cooper, Cyrus
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Lorentzon, Mattias
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Bea, Jennifer W.
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Carbone, Laura
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Cespedes Feliciano, Elizabeth M.
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Laddu, Deepika R.
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Schnatz, Peter F.
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Shadyab, Aladdin H.
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Stefanick, Marcia L
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Wactawski-Wende, Jean
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Crandall, Carolyn J.
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Johansson, Helena
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McCloskey, Eugene
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Harvey, Nicholas
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Kanis, John A.
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Liu, Enwu
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Cooper, Cyrus
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Lorentzon, Mattias
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Bea, Jennifer W.
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Carbone, Laura
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Cespedes Feliciano, Elizabeth M.
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Laddu, Deepika R.
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Schnatz, Peter F.
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Shadyab, Aladdin H.
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Stefanick, Marcia L
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Wactawski-Wende, Jean
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Crandall, Carolyn J.
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Johansson, Helena
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McCloskey, Eugene
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Harvey, Nicholas, Kanis, John A., Liu, Enwu, Cooper, Cyrus, Lorentzon, Mattias, Bea, Jennifer W., Carbone, Laura, Cespedes Feliciano, Elizabeth M., Laddu, Deepika R., Schnatz, Peter F., Shadyab, Aladdin H., Stefanick, Marcia L, Wactawski-Wende, Jean, Crandall, Carolyn J., Johansson, Helena and McCloskey, Eugene (2021) Predictive value of DXA appendicular lean mass for incident fractures, falls and mortality, independent of prior falls, FRAX and BMD: Findings from the Women’s Health Initiative (WHI). Journal of Bone and Mineral Research, 36 (4), 654-661. (doi:10.1002/jbmr.4239).

Record type: Article

Abstract

In the Women's Health Initiative (WHI), we investigated associations between baseline dual‐energy X‐ray absorptiometry (DXA) appendicular lean mass (ALM) and risk of incident fractures, falls, and mortality (separately for each outcome) among older postmenopausal women, accounting for bone mineral density (BMD), prior falls, and Fracture Risk Assessment Tool (FRAX®) probability. The WHI is a prospective study of postmenopausal women undertaken at 40 US sites. We used an extension of Poisson regression to investigate the relationship between baseline ALM (corrected for height2) and incident fracture outcomes, presented here for major osteoporotic fracture (MOF: hip, clinical vertebral, forearm, or proximal humerus), falls, and death. Associations were adjusted for age, time since baseline and randomization group, or additionally for femoral neck (FN) BMD, prior falls, or FRAX probability (MOF without BMD) and are reported as gradient of risk (GR: hazard ratio for first incident fracture per SD increment) in ALM/height2 (GR). Data were available for 11,187 women (mean [SD] age 63.3 [7.4] years). In the base models (adjusted for age, follow‐up time, and randomization group), greater ALM/height2 was associated with lower risk of incident MOF (GR = 0.88; 95% confidence interval [CI] 0.83–0.94). The association was independent of prior falls but was attenuated by FRAX probability. Adjustment for FN BMD T‐score led to attenuation and inversion of the risk relationship (GR = 1.06; 95% CI 0.98–1.14). There were no associations between ALM/height2 and incident falls. However, there was a 7% to 15% increase in risk of death during follow‐up for each SD greater ALM/height2, depending on specific adjustment. In WHI, and consistent with our findings in older men (Osteoporotic Fractures in Men [MrOS] study cohorts), the predictive value of DXA‐ALM for future clinical fracture is attenuated (and potentially inverted) after adjustment for femoral neck BMD T‐score. However, intriguing positive, but modest, associations between ALM/height2 and mortality remain robust. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

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nch FRAX WHI ALM paper 2021_01_05 R2 clean - Accepted Manuscript
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Accepted/In Press date: 23 December 2020
e-pub ahead of print date: 15 January 2021
Keywords: APPENDICULAR LEAN MASS, BMD, DXA, FRACTURE, FRAX, OSTEOPOROSIS: EPIDEMIOLOGY

Identifiers

Local EPrints ID: 446357
URI: http://eprints.soton.ac.uk/id/eprint/446357
ISSN: 0884-0431
PURE UUID: e00590ac-1e5d-4b7c-b4a8-471a981047c0
ORCID for Nicholas Harvey: ORCID iD orcid.org/0000-0002-8194-2512
ORCID for Cyrus Cooper: ORCID iD orcid.org/0000-0003-3510-0709

Catalogue record

Date deposited: 05 Feb 2021 17:31
Last modified: 26 Nov 2021 02:48

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Contributors

Author: Nicholas Harvey ORCID iD
Author: John A. Kanis
Author: Enwu Liu
Author: Cyrus Cooper ORCID iD
Author: Mattias Lorentzon
Author: Jennifer W. Bea
Author: Laura Carbone
Author: Elizabeth M. Cespedes Feliciano
Author: Deepika R. Laddu
Author: Peter F. Schnatz
Author: Aladdin H. Shadyab
Author: Marcia L Stefanick
Author: Jean Wactawski-Wende
Author: Carolyn J. Crandall
Author: Helena Johansson
Author: Eugene McCloskey

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