High intestinal calcium (Ca) absorption efficiency is positively associated with bone mass in a genetically diverse population of mice

Abstract

Habitual low Ca intake increases intestinal Ca absorption efficiency (Ca Abs) by a 1,25 dihydroxyvitamin D (1,25D)‐regulated mechanism. We investigated the role of Ca Abs on bone using a diverse population of 11 inbred mouse lines. Mice were fed a normal (0.5%) or low (0.25%) Ca diet from weaning to 3 mo of age and Ca Abs was determined by an oral gavage test. After correcting for the confounding effects of body size; Ca Abs, femur bone mineral density (BMD), trabecular bone volume fraction (BV/TV), and serum 1,25D varied significantly across the 11 lines at baseline and in low Ca adaptive response. Although Ca Abs was correlated to serum 1,25D levels (r=0.35, p<0.05), adaptation of Ca Abs to low Ca intake varied among the lines but was not strongly linked to diet‐induced changes in serum 1,25 D. Despite this heterogeneity, Ca Abs was significantly associated with femur BMD (r=0.17, p<0.05) and BV/TV (r=0.34, p<0.01). Duodenal transient receptor potential vanilloid member 6 and calbindin D9k mRNA levels were significantly correlated to each other (r=0.74), to serum 1,25D (r=0.44 and 0.39, respectively) and to Ca absorption (r=0.42 and 0.43, respectively), supporting the facilitated diffusion model. These results demonstrate the importance of Ca Abs and its adaptation to habitual low Ca intake for protecting bone mass during growth.Grant Funding Source: NIH Award ES19103 to JCF