Effect of the vitamin D receptor on bone geometry and strength during gestation and lactation in mice.
The vitamin D receptor (VDR) plays an important role in maintaining calcium homeostasis, acting as a mediator of transcellular calcium absorption and bone remodeling. Mice lacking a functional VDR have an abnormal skeletal phenotype, which is rescued by feeding a high-calcium diet. In this study, the role of the VDR in maintaining bone geometry and strength during gestation and lactation, when increased demands are placed on the calcium regulatory channels, was examined using a knockout mouse model. A rescue diet was used to counteract the decrease in calcium absorption in the gut that results from the absence of the VDR. Structural and compositional characteristics of the femur were compared between VDR knockout and wild-type mice following 9 and 16 days of gestation and 5 and 10 days of lactation using generalized linear models. Overall, the knockout mice had 6.5% lower cortical area, 23% lower trabecular volume fraction, and 9% lower bending stiffness than wild-type mice. However, the maximum moment of inertia of the femoral diaphyses, ultimate bending load, ash fraction, and trabecular thickness were not significantly different between knockout and wild-type mice. Only the mineral content exhibited interdependence between genotype and time point. Taken together, the results show that the VDR affects the quantity of mineralized bone tissue in the femoral diaphysis and metaphysis independently of reproductive status. However, the moments of inertia were similar between genotypes, resulting in similar bone stiffness and strength despite lower mineral content and cross-sectional area.
Korecki
Casey L
CL
Tissue Mechanics Laboratory, Department of Aerospace and Mechanical Engineering, The University of Notre Dame, 147 Multidisciplinary Research, Notre Dame, IN 46556, USA.
Zinser
Glendon
G
Liu
Xiangyi
X
Siedler
James
J
Welsh
JoEllen
J
Niebur
Glen L
GL
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002136:Calcium, Dietary / Q000008:administration & dosage / Q000378:metabolism; D018483:Diaphyses / Q000166:cytology / Q000378:metabolism; D005260:Female; D005269:Femur / Q000166:cytology / Q000502:physiology*; D007774:Lactation / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D008903:Minerals / Q000378:metabolism; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000502:physiology*; D018167:Receptors, Calcitriol / Q000235:genetics / Q000378:metabolism*
D002136:Calcium, Dietary; D008903:Minerals; D018167:Receptors, Calcitriol; D002118:Calcium