Knee loading accelerates bone healing in mice.
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.


BACKGROUND
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?


METHODS
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.


RESULTS
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.


CONCLUSIONS
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).
Zhang
Ping
P
Department of Biomedical Engineering, Indiana University-Purdue University, Indianapolis, IN 46202, USA.
Sun
Qiwei
Q
Turner
Charles H
CH
Yokota
Hiroki
H
D000818:Animals; D001861:Bone Regeneration / Q000502:physiology*; D005260:Female; D051379:Mice; D013977:Tibia / Q000293:injuries*; D016474:Weight-Bearing / Q000502:physiology*; D014945:Wound Healing / Q000502:physiology*
J Bone Joint Surg Am. 1998 Jun;80(6):868-78
9655105
J Bone Joint Surg Br. 2001 Mar;83(2):157-64
11284556
Clin Orthop Relat Res. 1989 Apr;(241):36-47
2924478
J Orthop Res. 2006 Aug;24(8):1679-86
16788988
Ann Biomed Eng. 2006 Oct;34(10):1600-6
17029032
Bone. 2003 Dec;33(6):960-9
14678856
Clin Orthop Relat Res. 2001 Apr;(385):192-8
11302314
J Bone Miner Metab. 2005;23(4):302-8
15981026
J Orthop Res. 2004 Sep;22(5):1079-85
15304282
J Orthop Res. 1984;1(4):431-49
6491792
Clin Orthop Relat Res. 1998 Oct;(355 Suppl):S163-78
9917637
Clin Orthop Relat Res. 1994 Apr;(301):281-90
8156689
J Orthop Res. 2003 Nov;21(6):1011-7
14554213
Osteoporos Int. 2002 Sep;13(9):688-700
12195532
J Orthop Trauma. 2001 Jan;15(1):54-60
11147689
Calcif Tissue Int. 2003 Jul;73(1):49-55
14506954
Bone. 2007 Feb;40(2):538-43
17070127
Calcif Tissue Int. 2003 Apr;72(4):498-504
12522665
Med Eng Phys. 2004 Jul;26(6):493-501
15234685
J Orthop Res. 2005 Sep;23(5):1022-8
15878254
Bone. 2007 May;40(5):1320-8
17344109
Clin Orthop Relat Res. 1998 Oct;(355 Suppl):S105-15
9917631
J Bone Joint Surg Am. 2003 Aug;85(8):1446-53
12925623
Osteoporos Int. 2005 Mar;16 Suppl 2:S36-43
15372141
Clin Orthop Relat Res. 1998 Oct;(355 Suppl):S132-47
9917634
J Orthop Sci. 2001;6(6):571-5
11793181
Alcohol Clin Exp Res. 2005 Oct;29(10):1769-76
16269906
J Bone Joint Surg Br. 1991 Jul;73(4):654-9
2071654
J Orthop Res. 1996 Jan;14(1):80-4
8618171
J Bone Joint Surg Br. 1985 Aug;67(4):650-5
4030869
J Orthop Res. 2002 Sep;20(5):1099-105
12382978
J Appl Physiol (1985). 2006 May;100(5):1441-2
16614362
J Orthop Res. 1987;5(1):29-35
3819909
Bone. 2001 Apr;28(4):423-9
11336924
J Bone Joint Surg Am. 1955 Oct;37-A(5):1035-68
13263349
J Appl Physiol (1985). 2006 May;100(5):1452-9
16410382