Prenatal but not continued postpartum vitamin D supplementation reduces maternal bone resorption as measured by C-terminal telopeptide of type 1 collagen without effects on other biomarkers of bone metabolism

TY - JOUR

T1 - Prenatal but not continued postpartum vitamin D supplementation reduces maternal bone resorption as measured by C-terminal telopeptide of type 1 collagen without effects on other biomarkers of bone metabolism

AU - Krupa, Christine

AU - Qamar, Huma

AU - O'Callaghan, Karen M.

AU - Onoyovwi, Akpevwe

AU - Mahmud, Abdullah Al

AU - Ahmed, Tahmeed

AU - Gernand, Alison D.

AU - Roth, Daniel E.

N1 - Funding Information: We would like to thank Hayley Craig-Barnes and Ashley St. Pierre of the Analytical Facility for Bioactive Molecules, The Hospital for Sick Children, Toronto, Canada for conducting 25-hydroxyvitamin D, PTH, FGF23, OPG, OC, and RANKL analyses. The roles and responsibilities of the authors are as follows: Daniel E. Roth: Conceptualization, Supervision, Methodology, Writing – Review & Editing. Christine Krupa: Formal Analysis, Visualization, Writing – Original Draft. Huma Qamar: Formal Analysis, Visualization, Writing – Review & Editing. Karen M. O'Callaghan: Supervision, Methodology, Writing – Review & Editing. Akpevwe Onoyovwi: Investigation, Writing – Review & Editing. Abdullah Al Mahmud: Supervision, Writing – Review & Editing. Tahmeed Ahmed: Writing – Review & Editing. Alison D. Gernand: Writing – Review & Editing. All authors read and approved the final manuscript and agree to be accountable for all aspects of the work. This research was supported by funding from the Bill and Melinda Gates Foundation (OPP1066764). Under the grant conditions of the Bill and Melinda Gates Foundation, a Creative Commons Attribution 4.0 Generic License has already been assigned to the Author Accepted Manuscript version that might arise from this submission. The funding agencies were not involved in the design, implementation, analysis or interpretation of the data. Funding Information: This research was supported by funding from the Bill and Melinda Gates Foundation ( OPP1066764 ). Under the grant conditions of the Bill and Melinda Gates Foundation, a Creative Commons Attribution 4.0 Generic License has already been assigned to the Author Accepted Manuscript version that might arise from this submission. The funding agencies were not involved in the design, implementation, analysis or interpretation of the data. Publisher Copyright: © 2023 The Authors

PY - 2024/3/31

Y1 - 2024/3/31

N2 - Vitamin D is a key regulator of bone mineral homeostasis and may modulate maternal bone health during pregnancy and postpartum. Using previously-collected data from the Maternal Vitamin D for Infant Growth (MDIG) trial in Dhaka, Bangladesh, we aimed to investigate the effects of prenatal and postpartum vitamin D 3 supplementation on circulating biomarkers of bone formation and resorption at delivery and 6 months postpartum. MDIG trial participants were randomized to receive a prenatal;postpartum regimen of placebo or vitamin D 3 (IU/week) as either 0;0 (Group A), 4200;0 (B), 16,800;0 (C), 28,000;0 (D) or 28,000;28,000 (E) from 17 to 24 weeks' gestation to 6 months postpartum. As this sub-study was not pre-planned, the study sample included MDIG participants who had data for at least 1 biomarker of interest at delivery or 6 months postpartum, with a corresponding baseline measurement (n = 690; 53 % of 1300 enrolled trial participants). Biomarkers related to bone turnover were measured in maternal venous blood samples collected at enrolment, delivery, and 6 months postpartum: osteoprotegerin (OPG), osteocalcin (OC), receptor activator nuclear factor kappa-B ligand (RANKL), fibroblast growth factor 23 (FGF23), procollagen type 1 N-terminal propeptide, (P1NP) and carboxy terminal telopeptide of type 1 collagen (CTx). Supplementation effects were expressed as percent differences between each vitamin D group and placebo with 95 % confidence intervals (95 % CI). Of 690 participants, 64 % had 25-hydroxyvitamin D concentrations (25OHD) <30 nmol/L and 94 % had 25OHD < 50 nmol/L at trial enrolment. At delivery, mean CTx concentrations were 27 % lower in group E versus placebo (95 % CI: −38, −13; P < 0.001), adjusting for enrolment concentrations. However, at 6 months postpartum, CTx concentrations were not statistically different in group E versus placebo (14 %; 95 % CI: −5.3, 37; P = 0.168), adjusting for delivery CTx concentrations. Effects on other biomarkers at delivery or postpartum were not statistically significant. In conclusion, prenatal high-dose vitamin D supplementation reduced bone resorption during pregnancy, albeit by only one biomarker, and without evidence of a sustained effect in the postpartum period. However, further evidence is needed to substantiate potential maternal bone health benefits of vitamin D in the postpartum period.

AB - Vitamin D is a key regulator of bone mineral homeostasis and may modulate maternal bone health during pregnancy and postpartum. Using previously-collected data from the Maternal Vitamin D for Infant Growth (MDIG) trial in Dhaka, Bangladesh, we aimed to investigate the effects of prenatal and postpartum vitamin D 3 supplementation on circulating biomarkers of bone formation and resorption at delivery and 6 months postpartum. MDIG trial participants were randomized to receive a prenatal;postpartum regimen of placebo or vitamin D 3 (IU/week) as either 0;0 (Group A), 4200;0 (B), 16,800;0 (C), 28,000;0 (D) or 28,000;28,000 (E) from 17 to 24 weeks' gestation to 6 months postpartum. As this sub-study was not pre-planned, the study sample included MDIG participants who had data for at least 1 biomarker of interest at delivery or 6 months postpartum, with a corresponding baseline measurement (n = 690; 53 % of 1300 enrolled trial participants). Biomarkers related to bone turnover were measured in maternal venous blood samples collected at enrolment, delivery, and 6 months postpartum: osteoprotegerin (OPG), osteocalcin (OC), receptor activator nuclear factor kappa-B ligand (RANKL), fibroblast growth factor 23 (FGF23), procollagen type 1 N-terminal propeptide, (P1NP) and carboxy terminal telopeptide of type 1 collagen (CTx). Supplementation effects were expressed as percent differences between each vitamin D group and placebo with 95 % confidence intervals (95 % CI). Of 690 participants, 64 % had 25-hydroxyvitamin D concentrations (25OHD) <30 nmol/L and 94 % had 25OHD < 50 nmol/L at trial enrolment. At delivery, mean CTx concentrations were 27 % lower in group E versus placebo (95 % CI: −38, −13; P < 0.001), adjusting for enrolment concentrations. However, at 6 months postpartum, CTx concentrations were not statistically different in group E versus placebo (14 %; 95 % CI: −5.3, 37; P = 0.168), adjusting for delivery CTx concentrations. Effects on other biomarkers at delivery or postpartum were not statistically significant. In conclusion, prenatal high-dose vitamin D supplementation reduced bone resorption during pregnancy, albeit by only one biomarker, and without evidence of a sustained effect in the postpartum period. However, further evidence is needed to substantiate potential maternal bone health benefits of vitamin D in the postpartum period.

UR - http://www.scopus.com/inward/record.url?scp=85179092781&partnerID=8YFLogxK

U2 - 10.1016/j.endmts.2023.100154

DO - 10.1016/j.endmts.2023.100154

M3 - Article

SN - 2666-3961

VL - 14

JO - Endocrine and Metabolic Science

JF - Endocrine and Metabolic Science

M1 - 100154

ER -