Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2013 Sep;93(3):211-21.
doi: 10.1007/s00223-013-9744-4. Epub 2013 May 25.

Adaptation of tibial structure and strength to axial compression depends on loading history in both C57BL/6 and BALB/c mice

Nilsson Holguin  1 , Michael D Brodt, Michelle E Sanchez, Akhilesh A Kotiya, Matthew J Silva
Affiliations

Adaptation of tibial structure and strength to axial compression depends on loading history in both C57BL/6 and BALB/c mice

Nilsson Holguin et al. Calcif Tissue Int. 2013 Sep.

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-old 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 a 10-s rest-insertion between cycles; the Cornell/HSS protocol applied 1,200 cycles/day, at 6.7 Hz, with a 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 (average + 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 that of AC by 65 % and that 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.

PubMed Disclaimer

Conflict of interest statement

All other authors have stated that they have no conflict of interest.

Figures

Figure 1
Figure 1
In vivo µCT measured (a) cortical bone volume at the mid-diaphyseal tibia and (b) trabecular bone volume fraction at the proximal tibial metaphysis. Data represent the differences between the final (6 week) and initial (0 week) scan for right (“loaded”) and left (contralateral) tibia. Compared to age-matched controls (AC), neither sham loading nor sham loading with transport affected tibial morphology.
Figure 2
Figure 2
In vivo µCT measured cortical bone volume at the mid-diaphyseal tibia of age-matched (AC), WashU loaded and Cornell/HSS loaded mice over 6 weeks. Independent of mouse strain, 6 weeks of WashU and Cornell/HSS loading increased cortical bone volume. Data represent differences [%] between right (loaded) and left (contralateral) tibia. Unlike WashU loading, Cornell/HSS loading increased bone volume at 3 weeks and produced greater changes in BALB/c mice than in C57BL/6. a: significant difference vs. AC, b: significant difference vs. WashU; †: significant difference vs 0 wk, ‡: significant difference between 6 and 3 wk; p<0.05.
Figure 3
Figure 3
At 6 weeks, in vivo µCT measured (a) cortical thickness at the tibial mid-diaphysis of age-matched control (AC), WashU loaded and Cornell/HSS loaded mice. From the same tibiae, (b) energy-to-fracture was determined by load-to-failure tests. Data represent differences [%] between right (“loaded”) and left (contralateral) tibia. Independent of mouse strain and waveform, 6 weeks of tibial loading produced greater cortical thickness. Cornell/HSS loading produced less relative cortical thickness than WashU loading in C57BL/6 but was not different than WashU loading in BALB/c. Energy-to-fracture was greater in tibiae of both mouse strains subjected to Cornell/HSS loading and BALB/c mice subjected to WashU loading. a: significant difference vs. AC, b: significant difference vs. WashU, # significant difference between C57BL/6 and BALB/c; p<0.05.
Figure 4
Figure 4
In vivo µCT measured trabecular bone volume fraction at the proximal tibial metaphysis of age-matched (AC), WashU loaded and Cornell/HSS loaded mice over 6 weeks. Data represent differences [%] between right (“loaded”) and left (contralateral) tibia. Independent of mouse strain, 6 weeks of Cornell/HSS loading produced greater trabecular bone volume fraction than WashU loading or AC. These differences were evident at 6 weeks but not 3 weeks. a: significant difference vs. AC, b: significant difference vs. WashU, †: significant difference vs 0 week, ‡: significant difference between 6 and 3 weeks; p<0.05.
Figure 5
Figure 5
At 6 weeks, in vivo µCT measured trabecular thickness at the proximal tibial metaphysis of age-matched (AC), WashU loaded and Cornell/HSS loaded mice. Data represent differences [%] between right (“loaded”) and left (contralateral) tibia. Independent of mouse strain and waveform, 6 weeks of tibial loading produced greater trabecular thickness. Cornell/HSS loading produced greater trabecular thickness than WashU loading in both mouse strains. a: significant difference vs. AC, b: significant difference vs. WashU, # significant difference between C57BL/6 and BALB/c; p<0.05.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Robling AG, Burr DB, Turner CH. Skeletal loading in animals. J Musculoskelet Neuronal Interact. 2001;1:249–262. - PubMed
    1. De Souza RL, Matsuura M, Eckstein F, Rawlinson SC, Lanyon LE, Pitsillides AA. Non-invasive axial loading of mouse tibiae increases cortical bone formation and modifies trabecular organization: a new model to study cortical and cancellous compartments in a single loaded element. Bone. 2005;37:810–818. - PubMed
    1. Fritton JC, Myers ER, Wright TM, van der Meulen MC. Loading induces site-specific increases in mineral content assessed by microcomputed tomography of the mouse tibia. Bone. 2005;36:1030–1038. - PubMed
    1. Robling AG, Castillo AB, Turner CH. Biomechanical and molecular regulation of bone remodeling. Annu Rev Biomed Eng. 2006;8:455–498. - PubMed
    1. Turner CH, Owan I, Takano Y. Mechanotransduction in bone: role of strain rate. Am J Physiol. 1995;269:E438–E442. - PubMed

Publication types

LinkOut - more resources