Adaptation of Tibial Structure and Strength to Axial Compression Depends on Loading History in Both C57BL/6 and BALB/c Mice

Abstract

Tibial compression can increase murine bone mass. However, loading protocols and mouse strains differ between studies which may contribute to conflicting results. We hypothesized that bone accrual is influenced more by loading history than by mouse strain or animal handling. The right tibiae of 4-month C57BL/6 and BALB/c mice were subjected to axial compression (10 N, 3 days/week, 6 weeks). Left tibiae served as contralateral controls to calculate relative changes [(Loaded-Control)/Control]. The WashU protocol applied 60 cycles/day, at 2 Hz, with 10 s rest-insertion between cycles; the Cornell/HSS protocol applied 1200 cycles/day, at 6.7 Hz, with 0.1 s rest-insertion. Because sham loading, sedation and transportation did not affect tibial morphology, unhandled mice served as age-matched controls (AC). Both loading protocols were anabolic for cortical bone, but Cornell/HSS loading elicited a more rapid response that was greater than WashU loading by 13%. By 6 weeks, cortical bone volume of each loading group was greater than of AC (avg. +16%) and not different from each other. Ultimate displacement and energy-to-fracture were greater in tibiae loaded by either protocol and ultimate force was greater with Cornell/HSS loading. At 6 weeks, independent of mouse strain, the WashU protocol produced minimal trabecular bone and the trabecular bone volume fraction of Cornell/HSS tibiae was greater than of AC by 65% and of WashU by 44%. We concluded that tibial adaptation to loading was more influenced by waveform than mouse strain or animal handling and therefore may have targeted similar osteogenic mechanisms in C57BL/6 and BALB/c mice.

Aging diminishes lamellar and woven bone formation induced by tibial compression in adult C57BL/6

“…To address this potential issue, we recently evaluated the response to tibial compression of young-adult BALB/c and C57Bl/6 mice and compared two previously published protocols [30]. The first protocol (which we labeled ‘WashU’) corresponds to the one used in our two prior BALB/c studies [17, 18], while the second protocol (which we labeled ‘Cornell/HSS’ based on work by others [22, 29]) corresponds to the one we used in the present study.…”

“…This protocol has been shown to be anabolic for cortical and trabecular bone in young-adult mice [22, 29, 30]. Based on a recent strain gauge analysis [28], we selected age-specific peak forces in order to generate peak periosteal strains of –2200 με and –3000 με at the cortical mid-shaft ( Fig.…”

Monitoring in vivo (re)modeling: A computational approach using 4D microCT data to quantify bone surface movements

“…The region-specific gain in resorption on the endocortical surface of the control bones needs further investigation, as this is not likely due to systemic effects from loading [47] or from stress-induced systemic effects arising from transport, sedation, etc. [48]. The increase in the short term formation response to loading, however, points to an increasing transfer function, i.e.…”

Transcriptional profiling of cortical versus cancellous bone from mechanically-loaded murine tibiae reveals differential gene expression

“…In mouse models in vivo compression of the tibia allows for the application of controlled loads and differentially increases bone mass in cortical (Ct) and cancellous (Cn) sites [8-10]. The molecular mechanisms behind this anabolic response to mechanical loading need to be determined and compared between cancellous and cortical bone.…”