Research ArticleMATERIALS SCIENCE

Lasting organ-level bone mechanoadaptation is unrelated to local strain

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Science Advances  06 Mar 2020:
Vol. 6, no. 10, eaax8301
DOI: 10.1126/sciadv.aax8301
  • Fig. 1 Loading modifies tibial curvature.

    (A) Study design demonstrating the temporal relationship between the sequence of the six in vivo scans (T1–T6) and tibial loading (nonloaded control and loaded mice shown). (B and C) Tibial curvature along the length in the control and loaded groups. Statistical differences in tibial curvature between different T’s within the control (B) and loaded (C) groups along the entire tibia shaft represented as a heat map. Red, P < 0.001; yellow, 0.001 ≤ P < 0.01; green, 0.01 ≤ P < 0.05; blue, P ≥ 0.05. Line graphs represent means ± SEM. (D and E) Pictorial representation of tibial curvature at T1, T4, and T6 in the control (D) and loaded group (E).

  • Fig. 2 Acute and chronic load-induced changes in predicted resistance to torsion (J) along the entire tibia length.

    (A) Acute mean J of control and loaded tibiae in female C57/Bl6 at T1–T4. (B) Chronic mean J of both groups at T1, T4–6 demonstrating chronic mechanoadaptation. Statistical significance of differences in J between different T’s within the group along the entire tibia shaft represented as a heat map. Red, P < 0.001; yellow, 0.001 ≤ P < 0.01; green, 0.01 ≤ P < 0.05; blue, P ≥ 0.05. Line graphs represent means ± SEM.

  • Fig. 3 Acute and chronic load-induced adaptation of CSA along the entire tibia length.

    (A) Acute mean CSA of control and loaded tibiae in female C57/Bl6 at T1–T4. (B) Chronic mean CSA of both groups at T1, T4–T6 demonstrating chronic mechanoadaptation. (C) Acute and chronic polar representation of CSA for the control and loaded groups. Statistical significance of differences in CSA between different T’s within the group along the entire tibia shaft represented as a heat map. Red, P < 0.001; yellow, 0.001 ≤ P < 0.01; green, 0.01 ≤ P < 0.05; blue, P ≥ 0.05. Line graphs represent means ± SEM.

  • Fig. 4 Validation of microCT-based 3D registration.

    (A) Image processing methodology to identify (re)modeling events. Two images obtained at different T’s are superimposed for rigid 3D registration to produce registered datasets. (B) These are subsequently used to calculate 3D formation and resorption bone (re)modeling responses. (C) Visualization of whole tibia showing location of the region selected for dynamic histomorphometric analysis of alizarin red double labeling (left pair of panels) and corresponding 3D microCT-based morphometry (right pair of panels), showing that areas of newly formed and eroded bone are found in comparable matching regions of the bone cortex. (D) MAR (μm/day) determined using 2D histomorphometry and 3D microCT-based morphometry. (E) Comparison between MAR assessed by histology and computationally visualized in a Bland-Altman plot.

  • Fig. 5 Acute and chronic load-induced bone formation/resorption (re)modeling responses in control and loaded mice.

    (A) Acute kinetic of bone formation and resorption in the control group. (B) Statistical heat maps illustrating acute differences between bone formation and resorption. (C) Unwrapped color-coded (blue, formation; red, resorption) endosteal and periosteal surfaces of acute load-related (re)modeling responses. (D) Chronic kinetic of bone formation and resorption in the control group. (E) Statistical heat maps illustrating chronic differences between bone formation and resorption. (F) Unwrapped color-coded (blue, formation; red, resorption) endosteal and periosteal surfaces of chronic load-related (re)modeling responses. Red, P < 0.001; yellow, 0.001 ≤ P < 0.01; green, 0.01 ≤ P < 0.05; blue, P ≥ 0.05. Line graphs represent means ± SEM.

  • Fig. 6 Load-induced modification in tibial architecture is integrated at the organ level.

    (A) Maximum principal tensile strain in unwrapped periosteal and endosteal surfaces of the loaded tibia at 25 to 35% and 50 to 60% of length at T1, T4, and T6. (B) The maximum principal tensile strain between 20 and 85% of tibial length at T1, T4, and T6. (C) Image processing methodology for correlation of the mechanical strain to the (re)modeling events. (D) Probability of acute (solid) and chronic (dashed) bone formation (top) and resorption (bottom) at 25 to 35% (magenta) and 50 to 60% (blue) of tibial length at each available tensile strain (maximum principal strain). Statistical heat maps demonstrate differences between acute and chronic formations at 50 to 60% and 25 to 35% length [(A) and (B), respectively] and acute and chronic resorptions at 50 to 60% and 25 to 35% length [(C) and (D), respectively]. Red, P < 0.001; yellow, 0.001 ≤ P < 0.01; green, 0.01 ≤ P < 0.05; blue, P ≥ 0.05. Line graphs represent means ± SEM.

Supplementary Materials

  • Supplementary material for this article is available at http://advances.sciencemag.org/cgi/content/full/6/10/eaax8301/DC1

    Fig. S1. Acute and chronic load-induced changes in tibial ellipticity along the entire tibia length.

    Fig. S2. Acute and chronic load-induced adaptation of mean cross-sectional thickness along the entire tibia length.

    Fig. S3. Load-displacement curve to demonstrate how 12-N load magnitude used in our studies relates to bone failure.

  • Supplementary Materials

    This PDF file includes:

    • Fig. S1. Acute and chronic load-induced changes in tibial ellipticity along the entire tibia length.
    • Fig. S2. Acute and chronic load-induced adaptation of mean cross-sectional thickness along the entire tibia length.
    • Fig. S3. Load-displacement curve to demonstrate how 12-N load magnitude used in our studies relates to bone failure.

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