Site specific bone adaptation response to mechanical loading

S.J. Kuruvilla, S.D. Fox, D.M. Cullen, M.P. Akhter

Creighton University, Omaha, NE, USA

Abstract
Over 25 million Americans suffer from osteoporosis. Bone size and strength depends both upon the level of adaptation due to physical activity (applied load), and genetics. We hypothesized that bone adaptation to loads differs among mice breeds and bone sites. Forty-five adult female mice from three inbred strains (C57BL/6 [B6], C3H/HeJ [C3], and DBA/2J [D2]) were loaded at the right tibia and ulna in vivo with non-invasive loading devices. Each loading session consisted of 99 cycles at a force range that induced ~2000 microstrain (με) at the mid-shaft of the tibia (2.5 to 3.5 N force) and ulna (1.5 to 2 N force). The right and left ulnae and tibiae were collected and processed using protocols for histological undecalcified cortical bone slides. Standard histomorphometry techniques were used to quantify new bone formation. The histomorphometric variables include percentage mineralizing surface (%MS), mineral apposition rate (MAR), and bone formation rate (BFR). Net loading response [right-left limb] was compared between different breeds at tibial and ulnar sites using two-way ANOVA with repeated measures (p<0.05). Significant site differences in bone adaptation response were present within each breed (p<0.005). In all the three breeds, the tibiae showed greater percentage MS, MAR and BFR than the ulna at similar in vivo load or mechanical stimulus (strain). These data suggest that the bone formation due to loading is greater in the tibiae than the ulnae. Although, no significant breed-related differences were found in response to loading, the data show greater trends in tibial bone response in B6 mice as compared to D2 and C3 mice. Our data indicate that there are site-specific skeletal differences in bone adaptation response to similar mechanical stimulus.

Keywords: Mechanical Loading, Bone Adaptation, B6, D2, C3, Mice