Dietary calcium and phosphate restriction in guinea-pigs during pregnancy: fetal mineralization induces maternal hypocalcaemia despite increased 1α,25-dihydroxycholecalciferol concentrations

Abstract

Guinea-pig fetuses at term are mineralized to a degree comparable with human fetuses, which makes the guinea-pig an attractive animal model to study maternal–fetal interactions with regard to Ca and phosphate (P) homeostasis. We studied non-pregnant and pregnant (day 57) vitamin D-replete guinea-pigs, fed either a normal guinea-pig chow with 9·6 g Ca/kg and 4·9 g P/kg or a study diet with 2 g Ca/kg and 1 g P/kg (low-Ca–P diet) for 7–8 weeks. Both pregnancy and the low-Ca–P diet decreased plasma concentrations of 25-hydroxycholecalciferol (25(OH)D3), but increased total and free 1α,25-dihydroxycholecalciferol (1,25(OH)2D3), strongly suggesting an additive stimulation of 1α-hydroxylase activity. Maternal and fetal 25(OH)D3and 1,25(OH)2D3levels were highly correlated (r0·82 and 0·92 respectively, P<0·001). Dual-energy absorption X-ray absorptiometry (DXA) showed that both pregnancy and the low-Ca–P diet decreased bone mineral density (BMD) of the maternal femur, particularly at the distal metaphysis. Despite higher 1,25(OH)2D3concentrations and lower BMD, pregnant animals on the low-Ca–P diet were hypocalcaemic; blood Ca2+levels were inversely correlated with the number of fetuses in this group (r-0·93, P<0·001). Fetal growth as well as mineralization (assessed by whole-body and femoral DXA, bone histomorphometry and plasma–bone osteocalcin measurements) were unaltered in the low-Ca–P group. In conclusion, fetal mineralization proceeds normally but induces maternal hypocalcaemia in guinea-pigs with dietary restriction of Ca and P.