Elizabeth M Curtis1, Camille Parsons1, Kate Maslin1,2, Stefania D'Angelo1, Rebecca J Moon1,3, Sarah R Crozier1, Fatma Gossiel4, Nicholas J Bishop5, Stephen H Kennedy6, Aris T Papageorghiou6, Robert Fraser7, Saurabh V Gandhi7, Ann Prentice8, Hazel M Inskip1,9, Keith M Godfrey1,9, Inez Schoenmakers10, M Kassim Javaid11, Richard Eastell4, Cyrus Cooper1,9,11, Nicholas C Harvey1,9. 1. Medical Research Council Lifecourse Epidemiology Centre, University of Southampton, Southampton, United Kingdom. 2. School of Nursing and Midwifery, University of Plymouth, Plymouth, United Kingdom. 3. Paediatric Endocrinology, University Hospitals Southampton National Health Service Foundation Trust, Southampton, United Kingdom. 4. Academic Unit of Bone Metabolism, University of Sheffield, Sheffield, United Kingdom. 5. Academic Unit of Child Health, Sheffield Children's Hospital, University of Sheffield, Sheffield, United Kingdom. 6. Nuffield Department of Women's & Reproductive Health, John Radcliffe Hospital, University of Oxford, Oxford, United Kingdom. 7. Department of Obstetrics and Gynaecology, Sheffield Hospitals National Health Service Trust, University of Sheffield, Sheffield, United Kingdom. 8. Medical Research Council Nutrition and Bone Health, University of Cambridge, Cambridge, United Kingdom. 9. National Institute for Health Research Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton National Health Service Foundation Trust, Southampton, United Kingdom. 10. Department of Medicine, Faculty of Medicine and Health Sciences, University of East Anglia, Norwich, United Kingdom. 11. National Institute for Health Research Oxford Biomedical Research Centre, University of Oxford, Oxford, United Kingdom.
Abstract
BACKGROUND: The pattern of change in maternal bone turnover throughout pregnancy is poorly characterized. OBJECTIVES: 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. METHODS: MAVIDOS (the Maternal Vitamin D Osteoporosis Study) is a randomized, double-blind, placebo-controlled trial of 1000 IU cholecalciferol/d compared with placebo from 14 weeks of gestation to birth. Maternal second-void urinary α- and β-CTX were measured (ELISA) at 14 and 34 weeks of gestation; DXA was performed within 2 wk postpartum. The Mann-Whitney Rank Sum test, 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: In total, 372 women had CTX and 25-hydroxyvitamin D [25(OH)D] measured in early and late pregnancy. CTX at 14 and 34 weeks of gestation were correlated in both placebo (r = 0.31) and cholecalciferol (r = 0.45) groups (P < 0.0001). Median CTX increased from 14 to 34 weeks of gestation in both groups (n = 372 total) [placebo (n = 188): from 223.6 to 449.7 μg/mmol creatinine; cholecalciferol (n = 184): from 222.3 to 419.3 μg/mmol creatinine; P = 0.03 for placebo compared with cholecalciferol difference in CTX at 34 weeks of gestation]. The conditional mean ± SD increase in CTX [z-score (SD)] from early to late pregnancy was greater in the placebo group (n = 188) than in the cholecalciferol group (n = 184) (placebo: 0.16 ± 0.92; cholecalciferol: -0.16 ± 1.06; P-difference < 0.01). Higher CTX at 34 weeks of gestation was associated, similarly in both groups, with lower maternal total hip and lumbar spine bone mineral content and bone mineral density (BMD) (e.g., lumbar spine BMD: β = -0.02 g · cm-2 · SD-1 increase in CTX; 95% CI: -0.027, -0.002 g · cm-2 · SD-1; P = 0.02, n = 283). CONCLUSIONS: Maternal urinary CTX, a bone resorption marker, rises through pregnancy, although to a lesser degree with gestational cholecalciferol supplementation, and is inversely associated with maternal bone mass postpartum.This trial was registered at www.isrctn.com as ISRCTN 82927713 and eudract.ema.europa.eu as EudraCT 2007-001716-23.
BACKGROUND: The pattern of change in maternal bone turnover throughout pregnancy is poorly characterized. OBJECTIVES: 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. METHODS: MAVIDOS (the Maternal Vitamin D Osteoporosis Study) is a randomized, double-blind, placebo-controlled trial of 1000 IU cholecalciferol/d compared with placebo from 14 weeks of gestation to birth. Maternal second-void urinary α- and β-CTX were measured (ELISA) at 14 and 34 weeks of gestation; DXA was performed within 2 wk postpartum. The Mann-Whitney Rank Sum test, 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: In total, 372 women had CTX and 25-hydroxyvitamin D [25(OH)D] measured in early and late pregnancy. CTX at 14 and 34 weeks of gestation were correlated in both placebo (r = 0.31) and cholecalciferol (r = 0.45) groups (P < 0.0001). Median CTX increased from 14 to 34 weeks of gestation in both groups (n = 372 total) [placebo (n = 188): from 223.6 to 449.7 μg/mmol creatinine; cholecalciferol (n = 184): from 222.3 to 419.3 μg/mmol creatinine; P = 0.03 for placebo compared with cholecalciferol difference in CTX at 34 weeks of gestation]. The conditional mean ± SD increase in CTX [z-score (SD)] from early to late pregnancy was greater in the placebo group (n = 188) than in the cholecalciferol group (n = 184) (placebo: 0.16 ± 0.92; cholecalciferol: -0.16 ± 1.06; P-difference < 0.01). Higher CTX at 34 weeks of gestation was associated, similarly in both groups, with lower maternal total hip and lumbar spine bone mineral content and bone mineral density (BMD) (e.g., lumbar spine BMD: β = -0.02 g · cm-2 · SD-1 increase in CTX; 95% CI: -0.027, -0.002 g · cm-2 · SD-1; P = 0.02, n = 283). CONCLUSIONS: Maternal urinary CTX, a bone resorption marker, rises through pregnancy, although to a lesser degree with gestational cholecalciferol supplementation, and is inversely associated with maternal bone mass postpartum.This trial was registered at www.isrctn.com as ISRCTN 82927713 and eudract.ema.europa.eu as EudraCT 2007-001716-23.
Authors: Cyrus Cooper; Nicholas C Harvey; Nicholas J Bishop; Stephen Kennedy; Aris T Papageorghiou; Inez Schoenmakers; Robert Fraser; Saurabh V Gandhi; Andrew Carr; Stefania D'Angelo; Sarah R Crozier; Rebecca J Moon; Nigel K Arden; Elaine M Dennison; Keith M Godfrey; Hazel M Inskip; Ann Prentice; M Zulf Mughal; Richard Eastell; David M Reid; M Kassim Javaid Journal: Lancet Diabetes Endocrinol Date: 2016-03-02 Impact factor: 32.069
Authors: Heyjun Park; Patsy M Brannon; Allyson A West; Jian Yan; Xinyin Jiang; Cydne A Perry; Olga Malysheva; Saurabh Mehta; Marie A Caudill Journal: Bone Date: 2016-12-08 Impact factor: 4.398
Authors: K S Jones; S Assar; D Harnpanich; R Bouillon; D Lambrechts; A Prentice; I Schoenmakers Journal: J Clin Endocrinol Metab Date: 2014-06-02 Impact factor: 5.958