Adaptation of bone and calcium metabolism to low dietary calcium (Ca) stress is affected by genetic background in mice

Abstract

We tested the hypothesis that Gene × Diet interactions influence adaptation of Ca and bone metabolism to low Ca intake using inbred mice. Male C57BL/6J (B6), DBA/2J (DBA), and PWK/PhJ (PWK) mice were fed diets containing adequate (0.5%) or low (0.25%) Ca levels from weaning until 3 mo (n=6–12 per group) when 45Ca absorption (Ca Abs) was assessed after an overnight fast (n=6 per group), serum was harvested for vitamin D metabolite levels, and femura were fixed for DEXA analysis of bone mineral density (BMD). Significant differences between the lines on the 0.5% Ca diet were observed for body weight (B6>DBA>PWK), BMD (DBA>B6>PWK), serum 25 hydroxyvitamin D (B6>DBA>PWK), serum 1,25 dihydroxyvitamin D (1,25 D; DBA>B6=PWK), and Ca Abs (B6>DBA=PWK). Ca restriction reduced BMD only in DBA mice (10.6% lower) and this was partly explained by their inability to increase serum 1,25 D and Ca Abs; low Ca diet increased serum 1,25 D and Ca Abs by 70% and 60%, respectively in B6 mice and by 97% and 11%, respectively in PWK mice. These data suggest there are genetic factors influencing basal levels of vitamin D and calcium metabolism in inbred mouse lines as well as the adaptation of Ca metabolism to dietary Ca restriction in DBA mice. Future forward genetic approaches will be necessary to identify the genetic variation responsible for these physiological differences. Supported by NIH Award DK054111 and funds from Purdue University