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

Am J Clin Nutr. 2021 Jul 23;nqab264. doi: 10.1093/ajcn/nqab264. Online ahead of print.


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.Clinical Trial Registry number and website: ISRCTN:82927713; EUDRACT:2007-001716-23.

Keywords: CTX; DXA; bone turnover; epidemiology; osteoporosis; pregnancy; vitamin D.