Vitamin D deficiency in guinea pigs: exacerbation of bone phenotype during pregnancy and disturbed fetal mineralization, with recovery by 1,25(OH)2D3 infusion or dietary calcium-phosphate supplementation.
Vitamin D (D) deficiency during human pregnancy appears to disturb fetal growth and mineralization, but fetal development is normal in D-deficient rats and vitamin D receptor gene-ablated mice. We used the guinea pig model to investigate maternal and fetal effects of D deficiency. Pregnant (Pr) and nonpregnant (NPr) animals were fed a D-replete (+D) or D-deficient diet (-D) for 8 weeks. We further studied whether the effects of a -D diet are reversed by continuous 1,25(OH)2D3 infusion (-D+1,25) and/or by a lactose-, Ca- and P-enriched D-deficient diet (-D+Ca/P). Bone analyses included histomorphometry of the proximal tibiae, dual-energy X-ray absorptiometry (DXA), and quantitative computed tomography (QCT) of the femora. Depletion of 25(OH)D3 and 1,25(OH)2D3 levels and the D-deficiency syndrome were more severe in pregnant animals. Indeed, Pr/-D but not NPr/-D guinea pigs were hypophosphatemic, and showed robust increases in growth plate width and osteoid surface and thickness; in addition, bone mineral density on DXA was lower in Pr/-D animals only, which was exclusively in cortical bone on QCT. Bone phenotype was partly normalized in Pr/-D+1,25 and Pr/-D+Ca/P animals. Compared with +D fetuses, -D fetuses had very low or undetectable 25(OH)D3 and 1,25(OH)2D3, were hypercalcemic and hypophosphatemic, and had lower osteocalcin levels. In addition, body weight and total body bone mineral content were 10-15% lower; histomorphometry showed hypertrophic chondrocyte zone expansion and hyperosteoidosis. 1,25(OH)2D3 levels were restored in -D+1,25 fetuses, and the phenotype was partially corrected. Similarly, the fetal +D phenotype was rescued in large part in -D+Ca/P fetuses, despite undetectable circulating 25(OH)D3 and 1,25(OH)2D3. We conclude that pregnancy markedly exacerbates D deficiency, and that augmenting Ca and P intake overrides the deleterious effects of D deficiency on fetal development.
Rummens
K
K
Department of Obstetrics and Gynecology, Katholieke Universiteit Leuven, 3000 Leuven, Belgium. katrien.rummens@uz.kuleuven.ac.be
van Bree
R
R
Van Herck
E
E
Zaman
Z
Z
Bouillon
R
R
Van Assche
F A
FA
Verhaeghe
J
J
D015502:Absorptiometry, Photon; D000818:Animals; D015519:Bone Density / Q000502:physiology; D002112:Calcifediol / Q000097:blood; D002113:Calcification, Physiologic / Q000502:physiology*; D002117:Calcitriol / Q000097:blood / Q000627:therapeutic use*; D002136:Calcium, Dietary / Q000008:administration & dosage*; D004195:Disease Models, Animal; D005314:Embryonic and Fetal Development / Q000502:physiology; D005260:Female; D006168:Guinea Pigs; D008431:Maternal-Fetal Exchange / Q000502:physiology*; D010710:Phosphates / Q000008:administration & dosage*; D011247:Pregnancy; D013977:Tibia / Q000187:drug effects / Q000378:metabolism; D014808:Vitamin D Deficiency / Q000178:diet therapy / Q000378:metabolism*
D002136:Calcium, Dietary; D010710:Phosphates; D002117:Calcitriol; D002112:Calcifediol