Serum 25-hydroxy vitamin D, calcium, phosphate, and magnesium levels in association with bone mineral density at the hip and lumbar spine in African breastfeeding women: a longitudinal evaluation

Abstract

The relationship between vitamin D status and serum calcium, phosphate, and magnesium levels, as well as bone mineral density, in African breastfeeding women remains understudied. Bone resorption is essential for maintaining mineral balance when demand for calcium, phosphate, and magnesium increases during breast milk production. We investigated the association between low serum levels of 25-hydroxyvitamin D (25(OH)D), calcium, phosphate, and magnesium and changes in bone mineral density (BMD) among postpartum women. Out of 540 young, healthy pregnant women not living with HIV enrolled in an open-label randomized controlled HIV pre-exposure prophylaxis (PrEP) trial between September 2018 and December 2019 in Durban, South Africa, 521 women with a mean (SD) age of 23.9 (4.7) years were included in this secondary data analysis. Women were randomized to either initiate tenofovir diphosphate fumarate (TDF)-containing PrEP in pregnancy or defer initiation to the time of breastfeeding cessation. Serum levels of calcium, magnesium, and phosphate, along with bone mineral density (BMD) of the total hip and lumbar spine, were measured in real-time at 6, 26, 54, and 74 weeks postpartum. We also measured serum 25-hydroxyvitamin D (25(OH)D) levels in stored samples collected in the second trimester of pregnancy and at 6 weeks postpartum. The mean (SD) serum 25(OH)D levels during pregnancy and postpartum were 72.4 (30.0) nmol/L and 69.9 (33.2) nmol/L, respectively. The prevalence of low vitamin D status [25(OH)D < 50 nmol/L] was 24.2% in pregnant women and 28.8% in the postpartum period, with 10.2% (95% CI 7.8–13.1) of women having serum levels of 25(OH)D < 30 nmol/L by 6 weeks postpartum. Serum 25(OH)D, total calcium, phosphate, and magnesium levels did not differ between randomization arms at all postpartum visits. The mean difference in BMD at the hip and lumbar spine between postpartum women with serum 25(OH)D < 50 nmol/L and those with > 50 nmol/L was not significant. At the 6, 26, 54, and 74 week visits, 292 (63.2%), 170 (36.8%), 101 (21.9%), and 54 (11.7%) women reported breastfeeding, respectively. During breastfeeding, 4.5%, 5.7%, and less than 1.5% of women had calcium, phosphate, and magnesium levels below the lower normal limit, respectively. Breastfeeding duration was positively associated with phosphate and magnesium levels. Serum calcium and magnesium levels did not correlate with BMD at the hip and lumbar spine. There was a significant inverse association between serum phosphate levels and BMD at the lumbar spine. Despite the high prevalence of vitamin D insufficiency or deficiency in our study, 25(OH)D levels did not predict changes in hip or spine bone mineral density. Higher serum phosphate levels were associated with lower lumbar spine BMD, suggesting bone resorption. This association was not observed for serum calcium or magnesium. In addition, there was no evidence of an association between TDF-PrEP and 25(OH)D or mineral metabolism in our study.