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

Guinea-pig fetuses at term are mineralized to a degree comparable with huma n fetuses, which makes the guinea-pig an attractive animal model to study m aternal-fetal interactions with regard to Ca and phosphate (P) homeostasis. We studied non-pregnant and pregnant (day 57) vitamin D-replete guinea-pig s, 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-hydr oxycholecalciferol (25(OH)D-3), but increased total and free 1 alpha ,25-di hydroxycholecalciferol (1,25(OH)(2)D-3), strongly suggesting an additive st imulation of 1 alpha -hydroxylase activity. Maternal and fetal 25(OH)D-3 an d 1,25(OH)(2)D-3 levels were highly correlated (r 0.82 and 0.92 respectivel y, 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 highe r 1,25(OH)(2)D-3 concentrations and lower BMD, pregnant animals on the low- Ca-P diet were hypocalcaemic; blood Ca2+ levels were inversely correlated w ith the number of fetuses in this group (r -0.93, P <0.001). Fetal growth a s well as mineralization (assessed by whole-body and femoral DXA, bone hist omorphometry and plasma-bone osteocalcin measurements) were unaltered in th e low-Ca-P group. In conclusion, fetal mineralization proceeds normally but induces maternal hypocalcaemia in guinea-pigs with dietary restriction of Ca and P.