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BMC Musculoskeletal Disorders

Open AccesResearch article

Knee loading stimulates cortical bone formation in murine femursPing Zhang1,2, Min Su1, Shigeo M Tanaka3and Hiroki Yokota*1,2

Address: 1Departments of Biomedical Engineering, Indiana University Purdue University Indianapolis, Fesler Hall 115, 1120 South Drive,Indianapolis IN 46202, USA, 2Department of Anatomy and Cell Biology, Indiana University School of Medicine, Fesler Hall 115, 1120 SouthDrive, Indianapolis IN 46202, USA and 3Graduate School of Natural Science and Technology, Kanazawa University, Ishikawa, Japan

Email: Ping Zhang - pizhang@iupui.edu; Min Su - su5@purdue.edu; Shigeo M Tanaka - shigeo@t.kanazawa-u.ac.jp;Hiroki Yokota* - hyokota@iupui.edu

* Corresponding author

Abstract

Background: Bone alters its architecture and mass in response to the mechanical environment,

and thus varying loading modalities have been examined for studying load-driven bone formation.

The current study aimed to evaluate the anabolic effects of knee loading on diaphyseal cortical bone

in the femur.

Methods: Using a custom-made piezoelectric loader, 0.5-N loads were laterally applied to the left

knee of C57/BL/6 mice at 5, 10, 15, and 20 Hz for 3 minutes per day for 3 consecutive days. Animals

were sacrificed for examination 13 days after the last loading. The contralateral femur was used asa non-loading control, and the statistical significance of loading effects was evaluated with p < 0.05.

Results: Although diaphyseal strains were measured as small as 12 strains, bone

histomorphometry clearly demonstrated frequency-dependent enhancement of bone formation.

Compared to a non-loading control, bone formation on the periosteal surface was significantlyenhanced. The loading at 15 Hz was most effective in elevating the mineralizing surface (1.7 x; p 30 Hz) can stimulate bone formation with alower level of strain [33,34]. Although the anabolicresponses at 20 Hz were insignificant, we do not have anyinformation on the effects of loading frequencies above20 Hz. Dependence of the observed anabolic responseson loading frequencies requires further investigationssince a daily loading cycle and a strain rate are consideredimportant factors, and mechanical testing should be con-

ducted to examine strengthening of bones with knee load-ing. Note that although loading at 20 Hz has the highestcycle number as well as the strain rate, it did not exhibitsuperior capability of bone formation. We did not detectany morphological damage on loaded knees, but morecareful inspection using molecular markers such asexpression and activities of matrix metalloproteinases willbe useful for detecting the maximum loads that do notcause any inflammation or evaluating potential regionalacceleratory phenomena [35-37]. Our preliminary studiesindicate that knee loading is able to enhance bone forma-

(A) Micro CT images (anterior and posterior views) of the mouse kneeFigure 7(A) Micro CT images (anterior and posterior views) of the mouse knee. The point "a" (femoral epicondyle) is located awayfrom the loader, compared to the point "b" in the tibial side. (B) Potential contributors involved in cortical bone formation withknee loading. The illustration includes alteration in intramedullary pressure, interstitial fluid flow, muscle contraction, andblood perfusion.

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tion throughout the femur including the femoral neck,and it can stimulate healing of wounded bone. Our futureanalyses include the role of osteoclastic activities as well asosteoblastic activities with knee loading. A prototypehuman knee joint loading supporter, designed and fabri-

cated for mechanical characterization, could be used infuture for a clinical trial [38].

ConclusionIn summary, the current mouse femur study demonstratesthat knee loading is an effective means to enhance corticalbone formation on the periosteal surface in the femoraldiaphysis with an in situ strain as small as ~10 strain atthe site of bone formation. Furthermore, the efficacy ofthe observed anabolic responses was dependent on theloading frequency. The results here extend our knowledgeof load-driven bone formation and the interplay betweenthe epiphysis and the diaphysis in the femur. Strengthen-

ing femurs contributes to preventing femoral fractures,and the described knee loading might provide a novelstrategy to develop mechanical therapies.

Competing interestsThe author(s) declare that they have no competing inter-ests.

Authors' contributionsPZ performed the animal experiments as well as bone his-tomorphometry and drafted the manuscript. MS carriedout the strain measurements. ST conducted part of theanimal experiments. HY designed the project and edited

the manuscript. All authors read and approved the finalmanuscript.

AcknowledgementsThe authors appreciate Dr. G.M. Malacinski for critical reading of the man-

uscript. This study was in part supported by NIH R03AG024596 and NIH

R01AR52144.

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Pre-publication historyThe pre-publication history for this paper can be accessedhere:

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