Strain differences in bone density and calcium metabolism between C3H/HeJ and C57BL/6J mice

Previous reports indicate that peak bone density is significantly higher in C3H/HeJ (C3H) than in C57BL/6J (C57BL) mice, making these two inbred strai ns useful models for studying the genetic basis for peak bone density. The following study was undertaken to examine whether strain differences in the bone density of C3H and C57BL mice are associated with differences in inte stinal calcium (Ca) absorption. Calcium absorption was measured by the bala nce technique and animals received two injections of fluorochromes 5 days a part before killing. Subsequently, the femurs were removed and, following m easurement of volumetric density, the left femur was divided into three equ al parts and the middle third served as the femoral cortical diaphysis. Fem ur diaphyseal volumetric bone density, ash, and Ca content were 10%, 29%, a nd 29% higher in C3H than in C57BL mice (p < 0.001), respectively. Bone len gth, periosteal mineral apposition rate, and periosteal bone formation rate of femoral diaphyseal cortical bone were not significantly different betwe en the two strains of mice, but the marrow area of C57BL mice was almost tw ofold that of C3H mice (p < 0.0001). Intestinal Ca absorption and 1,25-dihy droxyvitamin D [1,25(OH)(2)D]-stimulated Ca2+ uptake by intestinal mucosal cells were 38% and 51% higher in C3H than in C57BL mice p < 0.001), respect ively. Serum Ca and 1,25(OH)(2)D levels were 6% and 32% higher in C3H than in C57BL mice (p < 0.001), respectively, and the number of intestinal-occup ied vitamin D receptors was 51% higher in C3H than in C57BL mice (p < 0.01) . In a second experiment, three groups of C3H mice and three groups of C57B L mice were fed diets that contained 0.4%, 0.1%, or 0.02% Ca, and serum Ca, 1,25(OH)(2)D, parathyroid hormone (PTH), and intestinal Ca absorption meas ured. At all dietary Ca levels, C3H mice maintained positive Ca absorption and absorbed significantly more Ca than C57BL mice. In contrast, at low die tary Ca levels (0.1% and 0.02% Ca), C57BL mice maintained negative Ca absor ption. Low dietary Ca increased serum PTH significantly in C57BL but not in C3H mice, and decreased serum 1,25(OH)(2)D and Ca levels in both strains o f mice. Our findings indicate that the C57BL mice relied more on the mobili zation of Ca from bone to maintain extracellular Ca homeostasis than the C3 H mice. We conclude that strain differences in bone mass and density betwee n C3H and C57BL mice is expressed, in part, through the vitamin D and PTH e ndocrine systems and their effects on the maintenance of extracellular Ga h omeostasis. (C) 1999 by Elsevier Science Inc. All rights reserved.