Strain-Dependent Differences in Vertebral Bone Mass, Serum Osteocalcin, and Calcitonin in Calcium-Replete and -Deficient Mice

Abstract

The effects of dietary calcium intake on vertebral bone mass, composition, and turnover (calcium deposition and resorption) were determined in 10- and 14-week-old C57BL/6 (small) and SENCAR (large) mice. Total vertebral mass, percent ash, calcium, magnesium, and phosphorus were higher in SENCAR mice than in C57BL/6 mice at 10 weeks of age and after being fed 0.02% or 0.6% dietary calcium for 4 additional weeks. Relative calcium deposition was higher in C57BL/6 than in SENCAR mice, while relative calcium resorption was similar in both strains. The rate of resorption was higher in mice fed 0.02% dietary calcium than in those fed 0.6% dietary calcium. Thus, C57BL/6 mice gained vertebral calcium, while it remained unchanged or declined in SENCAR mice under conditions of both calcium depletion and calcium repletion. Serum osteocalcin (an index of bone formation) was higher in C57BL/6 mice than in SENCAR mice. Mathematically significant correlations between osteocalcin levels and vertebral calcium resorption and the net vertebral calcium loss were observed only in SENCAR mice. The serum calcitonin concentration was correlated with the amount of vertebral calcium resorbed in SENCAR mice, but not in C57BL/6 mice. Thus, vertebral resorption and formation are more tightly coupled in 10- to 14-week-old SENCAR mice than in C57BL/6 mice. In addition, remodeling appears to dominate vertebral calcium dynamics in SENCAR mice, while growth dominates in C57BL/6 mice during this period. Rodents have frequently been dismissed as potential models of bone aging based on the expectation that continued growth, rather than remodeling, dominates skeletal dynamics. These data clearly demonstrate that increases in body mass ("growth") are not invariably associated with continued vertebral growth. In this murine model, both heredity and dietary calcium intake modulate vertebral bone mass, turnover dynamics, and composition at sexual maturity. These differences in the development and regulation of vertebral bone mass in small C57BL/6 and large SENCAR mice suggest that animal, as well as clinical, models provide useful insights into the cellular and hormonal mechanisms of somatotype-dependent vertebral growth.