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 four-month old SAMP6 (osteoporotic) and SAMR1 (control) mice. Loading was applied daily (60 cycles/day, 5 days/wk) for 2 weeks at peak force levels that produced estimated endocortical strains of 1000 and 2000 με. In a separate group of mice, sham bending was applied. Comparisons were made between right (loaded) and left (non-loaded) 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, 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 non-loaded 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.

Comparing histological, vascular and molecular responses associated with woven and lamellar bone formation induced by mechanical loading in the rat ulna

“…Because our objective was to compare lamellar versus woven bone formation, we needed to ensure that the “lamellar” protocol did not produce any woven bone in the region where tissue was harvested for RNA extraction. Some previous reports of gene expression following mechanical loading have not described the type of bone that was induced [22, 36], although based on the loading model used (murine tibial bending) it is likely that the loading response would be a combination of periosteal woven bone and endocortical lamellar bone [38-39]. In this study we were able to use single-day loading protocols to compare and contrast the gene expression and vascular responses related to woven and lamellar bone formation.…”

Adaptive and injury response of bone to mechanical loading

“…The main limitation of this model is that direct pressure on the periosteal surfaces and overlying soft tissues often triggers a woven bone response which occurs as an “all or nothing” phenomenon (10), suggesting it is not proportional to the loading stimulus. The pressure-induced bone formation complicates interpretation of periosteal results(10,16) especially in smaller animals such as mice. For this reason, use of this model has declined and we do not recommend it.…”

Effect of Ovariectomy on the Tibia and Alveolar Bone in a Senescence-Accelerated Mouse-Prone 6 (SAMP6) Model

“…However, osteoporosis is an intrinsic disease; as a result, it is difficult to consider its causes-aging and decreased sex hormones-as independent from one another. Furthermore, bones are essentially organs that enable mobility, so the more an individual attempts exercise therapy for osteoporosis prevention and treatment, the better his or her bone's respond to mechanical stimulation 5,6) . Thus, while osteoporosis is characterized by the appearance of systemic symptoms, the extent of bone resorption is highly site specific; so it is difficult to make a detailed pathological examination at each location.…”