Postnatal and pubertal skeletal changes contribute predominantly to the differences in peak bone density between C3H/HeJ and C57BL/6J mice

Previous studies have shown that 60-70% of variance in peak bone density is determined genetically. The higher the peak bone density, the less likely an individual is to eventually develop osteoporosis. Therefore, the amount of bone accrued during postnatal and pubertal growth is an important determ ining factor in the development of osteoporosis. We evaluated the contribut ion of skeletal changes before, during, and after puberty to the developmen t of peak bone density in C3H/HeJ (C3H) and C57BL/6J (B6) mice. Volumetric bone density and geometric parameters at the middiaphysis of femora were me asured by peripheral quantitative computed tomography (pQCT) from days 7 to 56. Additionally, biochemical markers of bone remodeling in serum and bone extracts were quantified. Both B6 and C3H mice showed similar body and fem oral weights. B6 mice had greater middiaphyseal total bone area and thinner cortices than did C3H mice. within strains, males had thicker cortices tha n did females, C3H mice accumulated more minerals throughout the study, wit h the most rapid accumulation occurring postnatally (days 7-23) and during pubertal maturation (days 23-31). C3H mice had higher volumetric bone densi ty as early as day 7, compared with BG mice. Higher serum insulin-like grow th factor I (IGF-I) was present in C3H mice postnatally at day 7 and day 14 . Until day 31, B6 male and female mice had significantly higher serum oste ocalcin than C3H male and female mice, respectively. Alkaline phosphatase ( ALP) was found to be significantly higher in the bone extract of C3H mice c ompared with B6 mice at day 14. These data are consistent with and support the hypothesis that the greater amount of bone accrued during postnatal and pubertal growth in C3H mice compared with B6 mice may be caused by increas ed cortical thickness, increased endosteal bone formation, and decreased en dosteal bone resorption.