Maternal vitamin D biomarkers are associated with maternal and fetal bone turnover among pregnant women consuming controlled amounts of vitamin D, calcium, and phosphorus

Abstract

Vitamin D plays a central role in calcium homeostasis; however, its relationship with bone turnover during pregnancy remains unclear due to a lack of studies that have rigorously controlled for vitamin D and other nutrients known to influence bone metabolism. Similarly, prior investigations of the effect of pregnancy on bone turnover relative to the nonpregnant state may have been confounded by varying intakes of these nutrients. Nested within a controlled intake study, the present investigation sought to quantify associations between maternal vitamin D biomarkers and biochemical markers of bone turnover among pregnant (versus nonpregnant) women and their fetuses under conditions of equivalent and adequate intakes of vitamin D and related nutrients. Changes in markers of bone turnover across the third trimester were also examined. Healthy pregnant (26-29 wk gestation; n=26) and nonpregnant (n=21) women consumed 511IU vitamin D/d, 1.6g calcium/d, and 1.9g phosphorus/d for 10weeks while participating in a controlled feeding study featuring two choline doses. Based on linear mixed models adjusted for influential covariates (e.g., BMI, ethnicity, and season), pregnant women had 50-150% higher (P<0.001) concentrations of bone resorption markers than nonpregnant women. Among pregnant women, increases in maternal 25(OH)D across the study period were associated (P<0.020) with lower osteocalcin and deoxypyridinoline at study-end, and higher fetal osteocalcin. In addition, maternal free 25(OH)D, 1,25(OH)₂D and 24,25(OH)₂D tended to be negatively associated (P≤0.063) with maternal NTx at study-end, and maternal free 25(OH)D and 24,25(OH)₂D were positively associated (P≤0.021) with fetal CTx. Similarly, maternal 3-epi-25(OH)D₃ was negatively related (P≤0.037) to maternal NTx and deoxypyridinoline at study-end. These declines in bone resorption markers resulting from higher vitamin D biomarker concentrations among pregnant women coincided with increases in their albumin-corrected serum calcium concentrations, indicating that calcium transfer to the fetus was uncompromised. Notably, none of these associations achieved statistical significance among nonpregnant women. Overall, our study findings suggest that achieving higher maternal concentrations of vitamin D biomarkers might attenuate third-trimester bone resorption while ensuring sufficient calcium delivery to the fetus.

Keywords: 25-hydroxyvitamin D; Bone metabolism; Bone turnover; Calcium homeostasis; Pregnancy; Vitamin D.

Figure 1

Biochemical markers of bone turnover in pregnant and nonpregnant women consuming equivalent and adequate amounts of vitamin D, calcium, and phosphorus for 10 weeks. Values are predicted means after adjusted for covariates. Baseline values are represented as open shapes, while study-end values are represented as closed shapes. Different letters (i.e., a>b>c) indicate significant differences (P<0.05) in bone markers between pregnant and nonpregnant groups at each study time point. An asterisk (*) indicates a significant change (P<0.05) in the concentrations of bone markers within each group throughout the study, and a long cross symbol (†) indicates a borderline significant change (P=0.054). (A) iPTH, intact parathyroid hormone; (B) CTx, carboxy-terminal cross-linking telopeptide of type 1 collagen; (C) NTx, amino-terminal cross-linking telopeptide of type 1 collagen; (D) Urinary DPD/Creatinine, urinary deoxypyridinoline/creatinine; (E) OC, osteocalcin; (F) ALP, alkaline phosphatase; (G) Albumin-adjusted serum calcium; (H) Phosphorus.

Figure 2

(A, B) Bone turnover markers, OC and CTx, in pregnant women (baseline and study-end) and their fetuses (delivery). Values are means (95% CIs). Different letters (i.e., a>b>c) indicate significant differences (P<0.05) in OC and CTx between pregnant women and their fetuses.