Knee loading accelerates bone healing in mice.

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Knee loading is an anabolic loading modality that applies lateral loads to the knee. This study shows that loads applied to the proximal tibial epiphysis stimulate healing of surgically generated wounds in the tibial diaphysis. Wound healing is sensitive to mechanical stimulation such as various forms of stress and different magnitudes of strain. Knee loading has been shown to induce anabolic responses to murine tibias and femora when a strain of 10-20 mustrain is applied at the site of new bone formation. The object of this study was to address a question: does knee loading accelerate closure of open wounds in the tibia? Fifty-three C57/BL/6 female mice were used. A surgical wound (0.5 mm in diameter) was generated in the left tibia (loaded) and the right tibia (sham-loaded control). From the fourth postoperative day, knee loading was performed to the left knee with a custom-made piezoelectric loader for 3 min/d for 3 consecutive days. The peak-to-peak force was 0.5 N. Animals were killed 1, 2, or 3 wk after surgery, and the healing process was evaluated with muCT, pQCT, and bone histomorphometry with calcein labeling. The measured strain was <20 mustrain with 0.5-N force regardless of the presence or absence of surgical wounds. Compared with sham-loaded controls, the results showed load-driven acceleration of wound healing. First, muCT data revealed that knee loading reduced the size of surgical wounds by 13% (p < 0.01; 1 wk), 25% (p < 0.001; 2 wk), and 15% (p < 0.01; 3 wk). Second, pQCT data indicated that total BMD and BMC and cortical BMD and BMC were significantly increased in the third postoperative week. Last, bone histomorphometry revealed that bone formation was stimulated from the site proximal (close to the knee) to the wound. The reparative and remodeling phases of wound healing were enhanced by loads applied to the knee without inducing significant in situ strain at the site of wounds. Noninvasive knee loading might therefore be useful clinically to stimulate bone healing in the entire tibia along its length (including cast immobilized wounds).