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Bone turnover in pregnancy, measured by urinary C-terminal telopeptide of type I collagen (CTX), is influenced by vitamin D supplementation and is associated with maternal bone health: findings from the MAVIDOS trial

Bone turnover in pregnancy, measured by urinary C-terminal telopeptide of type I collagen (CTX), is influenced by vitamin D supplementation and is associated with maternal bone health: findings from the MAVIDOS trial
Bone turnover in pregnancy, measured by urinary C-terminal telopeptide of type I collagen (CTX), is influenced by vitamin D supplementation and is associated with maternal bone health: findings from the MAVIDOS trial
Background: the pattern of change in maternal bone turnover throughout pregnancy is poorly characterized.Objective: we investigated changes across pregnancy in a marker of maternal bone resorption, urinary C-terminal telopeptide of type I collagen (CTX), the influence of gestational vitamin D supplementation, and associations between CTX and maternal postnatal bone indices.
Design: the Maternal Vitamin D Osteoporosis Study (MAVIDOS) is a randomized, double-blind, placebo-controlled trial of 1000 IU/day cholecalciferol vs placebo from 14 weeks’ gestation to birth. Maternal second void urinary α- and β-CTX were measured (Enzyme Linked Immunosorbent Assay, ELISA) at 14 and 34 weeks’ gestation; DXA was performed within 2 weeks post-partum. Mann-Whitney rank sum, Spearman's rank correlation and linear regression were used to compare median CTX values within and between groups from early to late pregnancy, and associations with maternal bone outcomes.
Results: 372 women had CTX and 25(OH)-vitamin D measured in early and late pregnancy. CTX at 14 and 34 weeks’ gestation were correlated in both placebo (r = 0.31) and cholecalciferol (r = 0.45) groups (P < 0.0001). Median CTX(μg/mmol creatinine) increased from 14 to 34 weeks’ gestation in both groups (n = 372 total) [placebo (n = 188) 223.6 to 449.7; cholecalciferol (n = 184) 222.3 to 419.3; P = 0.03 for placebo vs cholecalciferol difference in CTX at 34 weeks’ gestation]. The conditional increase in CTX(SD) from early to late pregnancy was greater in the placebo group (n = 188) than in the cholecalciferol group (n = 184) [placebo, mean(SD) 0.16(0.92); cholecalciferol, -0.16(1.06); p difference < 0.01]. Higher CTX at 34 weeks’ gestation was associated, similarly in both groups, with lower maternal total hip and lumbar spine bone mineral content (BMC) and bone mineral density, e.g., lumbar spine BMD [β= -0.02 g/cm2/SD increase in CTX; 95%CI: -0.027, -0.002; P = 0.02, n = 283].
Conclusions: maternal urinary CTX, a bone resorption marker, rises through pregnancy, though to a lesser degree with gestational cholecalciferol supplementation, and is inversely associated with maternal bone mass post-partum.
0002-9165
Curtis, Elizabeth
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Parsons, Camille
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Maslin, Kate
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D'angelo, Stefania
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Moon, Rebecca
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Crozier, Sarah
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Gossiel, Fatma
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Bishop, Nicholas J.
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Kennedy, Stephen
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Papageorghiou, Aris T.
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Fraser, Robert
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Gandhi, Saurabh V.
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Prentice, Ann
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Inskip, Hazel
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Godfrey, Keith
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Schoenmakers, Inez
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Kassim Javaid, M.
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Eastell, Richard
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Cooper, Cyrus
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Harvey, Nicholas
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Curtis, Elizabeth
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Parsons, Camille
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Maslin, Kate
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D'angelo, Stefania
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Moon, Rebecca
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Crozier, Sarah
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Gossiel, Fatma
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Bishop, Nicholas J.
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Kennedy, Stephen
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Fraser, Robert
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Gandhi, Saurabh V.
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Prentice, Ann
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Inskip, Hazel
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Godfrey, Keith
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Schoenmakers, Inez
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Kassim Javaid, M.
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Eastell, Richard
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Cooper, Cyrus
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Harvey, Nicholas
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Curtis, Elizabeth, Parsons, Camille, Maslin, Kate, D'angelo, Stefania, Moon, Rebecca, Crozier, Sarah, Gossiel, Fatma, Bishop, Nicholas J., Kennedy, Stephen, Papageorghiou, Aris T., Fraser, Robert, Gandhi, Saurabh V., Prentice, Ann, Inskip, Hazel, Godfrey, Keith, Schoenmakers, Inez, Kassim Javaid, M., Eastell, Richard, Cooper, Cyrus and Harvey, Nicholas (2021) Bone turnover in pregnancy, measured by urinary C-terminal telopeptide of type I collagen (CTX), is influenced by vitamin D supplementation and is associated with maternal bone health: findings from the MAVIDOS trial. American Journal of Clinical Nutrition. (doi:10.1093/ajcn/nqab264).

Record type: Article

Abstract

Background: the pattern of change in maternal bone turnover throughout pregnancy is poorly characterized.Objective: we investigated changes across pregnancy in a marker of maternal bone resorption, urinary C-terminal telopeptide of type I collagen (CTX), the influence of gestational vitamin D supplementation, and associations between CTX and maternal postnatal bone indices.
Design: the Maternal Vitamin D Osteoporosis Study (MAVIDOS) is a randomized, double-blind, placebo-controlled trial of 1000 IU/day cholecalciferol vs placebo from 14 weeks’ gestation to birth. Maternal second void urinary α- and β-CTX were measured (Enzyme Linked Immunosorbent Assay, ELISA) at 14 and 34 weeks’ gestation; DXA was performed within 2 weeks post-partum. Mann-Whitney rank sum, Spearman's rank correlation and linear regression were used to compare median CTX values within and between groups from early to late pregnancy, and associations with maternal bone outcomes.
Results: 372 women had CTX and 25(OH)-vitamin D measured in early and late pregnancy. CTX at 14 and 34 weeks’ gestation were correlated in both placebo (r = 0.31) and cholecalciferol (r = 0.45) groups (P < 0.0001). Median CTX(μg/mmol creatinine) increased from 14 to 34 weeks’ gestation in both groups (n = 372 total) [placebo (n = 188) 223.6 to 449.7; cholecalciferol (n = 184) 222.3 to 419.3; P = 0.03 for placebo vs cholecalciferol difference in CTX at 34 weeks’ gestation]. The conditional increase in CTX(SD) from early to late pregnancy was greater in the placebo group (n = 188) than in the cholecalciferol group (n = 184) [placebo, mean(SD) 0.16(0.92); cholecalciferol, -0.16(1.06); p difference < 0.01]. Higher CTX at 34 weeks’ gestation was associated, similarly in both groups, with lower maternal total hip and lumbar spine bone mineral content (BMC) and bone mineral density, e.g., lumbar spine BMD [β= -0.02 g/cm2/SD increase in CTX; 95%CI: -0.027, -0.002; P = 0.02, n = 283].
Conclusions: maternal urinary CTX, a bone resorption marker, rises through pregnancy, though to a lesser degree with gestational cholecalciferol supplementation, and is inversely associated with maternal bone mass post-partum.

Text
MAVIDOS CTX AJCN_R2 2021_06_29_R2_final - Accepted Manuscript
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Accepted/In Press date: 19 July 2021
Published date: 23 July 2021
Additional Information: Supported by Arthritis Research UK and Medical Research Council (MRC) grant 4050502589 (to CC), Bupa Foundation, UK Royal Osteoporosis Society, National Institute for Health Research (NIHR) Southampton Biomedical Research Center grant IS-BRC-1215-20004 (to CC), University of Southampton and University Hospital Southampton National Health Service Foundation Trust, and NIHR Oxford Biomedical Research Centre, University of Oxford. EMC is supported by Wellcome Trust grant 201268/Z/16/Z. AP is funded by the MRC (programme code U105960371). KMG is supported by NIHR Senior Investigator grant NF-SI-0515-10042, NIHR Southampton 1000 Days Plus Global Nutrition Research Group grant 17/63/154, the European Union (Erasmus+ Programme Early Nutrition eAcademy Southeast Asia-573651-EPP-1-2016-1-DE-EPPKA2-CBHE-JP and ImpENSA 598488-EPP-1-2018-1-DE-EPPKA2-CBHE-JP), US National Institute on Aging of the NIH award U24AG047867, and UK Economic and Social Research Council and Biotechnology and Biological Sciences Research Council (BBSRC) award nES/M00919X/1. The work leading to these results was supported by the European Union's Seventh Framework Programme (FP7/2007–2013), projects EarlyNutrition and ODIN under grants 289346 and 613977, and by the BBSRC (HDHL-Biomarkers, BB/P028179/1), as part of the ALPHABET project, supported by an award made through the ERA-Net on Biomarkers for Nutrition and Health (ERA HDHL), Horizon 2020 Framework Programme grant 696295 (to NCH). Members of the authorship contribute to the European Reference Network on Rare Bone Diseases. We are extremely grateful to Merck GmbH for the kind provision of the Vigantoletten supplement. Merck GmbH had no role in the trial execution, data collection, analysis, or manuscript preparation. The authors had full access to all study data.

Identifiers

Local EPrints ID: 450571
URI: http://eprints.soton.ac.uk/id/eprint/450571
ISSN: 0002-9165
PURE UUID: beccbc2f-f811-4cd6-84c2-f66211241bc5
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 Sarah Crozier: ORCID iD orcid.org/0000-0002-9524-1127
ORCID for Hazel Inskip: ORCID iD orcid.org/0000-0001-8897-1749
ORCID for Keith Godfrey: ORCID iD orcid.org/0000-0002-4643-0618
ORCID for Cyrus Cooper: ORCID iD orcid.org/0000-0003-3510-0709
ORCID for Nicholas Harvey: ORCID iD orcid.org/0000-0002-8194-2512

Catalogue record

Date deposited: 04 Aug 2021 16:33
Last modified: 11 Nov 2021 02:53

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Contributors

Author: Camille Parsons
Author: Kate Maslin
Author: Stefania D'angelo ORCID iD
Author: Rebecca Moon
Author: Sarah Crozier ORCID iD
Author: Fatma Gossiel
Author: Nicholas J. Bishop
Author: Stephen Kennedy
Author: Aris T. Papageorghiou
Author: Robert Fraser
Author: Saurabh V. Gandhi
Author: Ann Prentice
Author: Hazel Inskip ORCID iD
Author: Keith Godfrey ORCID iD
Author: Inez Schoenmakers
Author: M. Kassim Javaid
Author: Richard Eastell
Author: Cyrus Cooper ORCID iD
Author: Nicholas Harvey ORCID iD

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