Mechanical Stimulation of Bone Formation is Normal in the SAMP6 Mouse

Abstract

With aging, the skeleton may have diminished responsiveness to mechanical stimulation. The senescence-accelerated mouse SAMP6 has many features of senile osteoporosis and is thus a useful model to examine how the osteoporotic skeleton responds to mechanical loading. We performed in vivo tibial bending on 4-month-old SAMP6 (osteoporotic) and SAMR1 (control) mice. Loading was applied daily (60 cycles/day, 5 days/week) for 2 weeks at peak force levels that produced estimated endocortical strains of 1,000 and 2,000 microepsilon In a separate group of mice, sham bending was applied. Comparisons were made between right (loaded) and left (nonloaded) tibiae. Tibial bone marrow cells were cultured under osteogenic conditions and stained for alkaline phosphatase (ALP) and alizarin red (ALIZ) at 14 and 28 days, respectively. Tibiae were then embedded in plastic and sectioned, and endocortical bone formation was assessed based on calcein labels. Tibial bending did not alter the osteogenic potential of the marrow as there were no significant differences in ALP or ALIZ staining between loaded and nonloaded bones. Tibial bending activated the formation of endocortical bone in both SAMP6 and SAMR1 mice, whereas sham bending did not elicit an endocortical response. Both groups of mice exhibited bending strain-dependent increases in bone formation rate. We found little evidence of diminished responsiveness to loading in the SAMP6 skeleton. In conclusion, the ability of the SAMP6 mouse to respond normally to an anabolic mechanical stimulus distinguishes it from chronologically aged animals. This finding highlights a limitation of the SAMP6 mouse as a model of senile osteoporosis.