Cortical Bone Growth in Response to Local Strain Environment

Osteoporosis is a disease characterized by skeletal fragility resulting in increased risk of fracture. Millions of people are affected by osteoporotic fractures every year. Pharmaceutical drugs available in the current market have side-effects coming from long-term administration and adherence. While mechanical loading is known to be a critical factor during cortical bone growth, the type of mechanical loading a bone is subjected to during normal physiological condition can also affect bone development process.

It still is unclear whether tensile or compressive strains have better outcome in young cortical bone growth. In this study, juvenile sheep femur were scanned using micro-Computed Tomography (CT). Thickness and density were computed via image processing in MATLAB. Bone volume fraction (BV/TV) was determined through image processing in Amira. Samples along the longitudinal axis of diaphysis were machined and mechanically tested in three-point bending. Mechanical testing was done in two configurations: stain mode specific (SMS) (testing samples in habitual loading) and non-strain mode specific (testing samples in loading they are normally subjected to). Structure, composition, and material properties were investigated in two specific quadrants of femur diaphysis: anterior side subjected to tensile loading, and posterior side subjected to compressive loading during physiological activities.

There was no significant difference between cortical thickness and density of anterior and posterior quadrants. BV/TV was significantly higher in anterior quadrant compared to posterior quadrant in proximal diaphysis (p=0.016). Flexural modulus of anterior quadrant was higher than posterior only in distal diaphysis when tested in non-SMS condition (p=8E3). Anterior quadrant was always stronger than posterior quadrant regardless of testing mode (SMS: p=8E-3 proximal and middle diaphysis, non-SMS: p=8E-3 middle and distal diaphysis). Poor correlation was detected between density-modulus and density-strength (R² = 7.6% and R² = 11.3% respectively). BV/TV was more important in explaining the material properties than density: BV/TV-modulus R² = 10.7% and BV/TV-strength R² = 30.7%.

Year	Entry
2013	Weatherholt AM, Fuchs RK, Warden SJ. Cortical and trabecular bone adaptation to incremental load magnitudes using the mouse tibial axial compression loading model. Bone. January 2013;52(1):372-379.
1993	Riggs CM, Lanyon LE, Boyde A. Functional associations between collagen fibre orientation and locomotor strain direction in cortical bone of the equine radius. Anat Embryol. March 1993;187(3):231-238.
1979	Lanyon LE, Magee PT, Baggott DG. The relationship of functional stress and strain to the processes of bone remodelling: an experimental study on the sheep radius. J Biomech. 1979;12(8):593-600.
1976	Lanyon LE, Baggott DG. Mechanical function as an influence on the structure and form of bone. J Bone Joint Surg. November 1976;58B(4):436-443.
2015	Zimmermann EA, Busse B, Ritchie RO. The fracture mechanics of human bone: influence of disease and treatment. BoneKEy Rep. September 2015;4:743.
1994	Torrance AG, Mosley JR, Suswillo RFL, Lanyon LE. Noninvasive loading of the rat ulna in vivo induces a strain-related modeling response uncomplicated by trauma or periostal pressure. Calcif Tiss Int. March 1994;54(3):241-247.
2000	Knothe Tate ML, Steck R, Forwood MR, Niederer P. In vivo demonstration of load-induced fluid flow in the rat tibia and its potential implications for processes associated with functional adaptation. J Exp Biol. September 2000;203(18):2737-2745.
2003	Lieberman DE, Pearson OM, Polk JD, Demes B, Crompton AW. Optimization of bone growth and remodeling in response to loading in tapered mammalian limbs. J Exp Biol. September 15, 2003;206(18):3125-3138.
2002	Bass SL, Saxon L, Daly RM, Turner CH, Robling AG, Seeman E, Stuckey S. The effect of mechanical loading on the size and shape of bone in pre-, peri-, and postpubertal girls: a study in tennis players. J Bone Miner Res. December 2002;17(12):2274-2280.
2005	De Souza RL, Matsuura M, Eckstein F, Rawlinson SCF, 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. December 2005;37(6):810-818.
1974	Evans FG, Vincentelli R. Relations of the compressive properties of human cortical bone to histological structure and calcification. J Biomech. January 1974;7(1):1-10.
2017	Khosla S, Hofbauer LC. Osteoporosis treatment: recent developments and ongoing challenges. Lancet Diabetes Endocrinol. November 2017;5(11):898-907.
2014	Warden SJ, Roosa SMM, Kersh ME, Hurd AL, Fleisig GS, Pandy MG, Fuchs RK. Physical activity when young provides lifelong benefits to cortical bone size and strength in men. Proc Natl Acad Sci USA. April 8, 2014;111(14):5337-5342.
1990	Frost HM. Skeletal structural adaptations to mechanical usage (SATMU), I: redefining Wolff's law: the bone modeling problem. Anat Rec. 1990;226(4):403-413.
2011	Rachner TD, Khosla S, Hofbauer LC. Osteoporosis: now and the future. Lancet. April 9, 2011;377(9773):1276-1287.
1993	Turner CH, Burr DB. Basic biomechanical measurements of bone: a tutorial. Bone. 1993;14(4):595-608.
2004	Warden SJ, Turner CH. Mechanotransduction in the cortical bone is most efficient at loading frequencies of 5–10 hz. Bone. February 2004;34(2):261-270.
1986	Wolff J. The Law of Bone Remodelling. Maquet P, Furlong R, trans. New York, NY: Springer; 1986.
2015	Wegst UGK, Bai H, Saiz E, Tomsia AP, Ritchie RO. Bioinspired structural materials. Nat Mater. January 2015;14(1):23-36.
2001	Robling AG, Duijvelaar KM, Geevers JV, Ohashi N, Turner CH. Modulation of appositional and longitudinal bone growth in the rat ulna by applied static and dynamic force. Bone. August 2001;29(2):105-113.
2008	Seeman E. Bone quality: the material and structural basis of bone strength. J Bone Min Metab. 2008;26(1):1-8.
2013	Andersen TL, Abdelgawad ME, Kristensen HB, Hauge EM, Rolighed L, Bollerslev J, Kjærsgaard-Andersen P, Delaisse J-M. Understanding coupling between bone resorption and formation: are reversal cells the missing link? Am J Pathol. July 2013;183(1):235-246.
1997	Gross TS, Edwards JL, Mcleod KJ, Rubin CT. Strain gradients correlate with sites of periosteal bone formation. J Bone Miner Res. June 1997;12(6):982-988.
2009	Robling AG, Turner CH. Mechanical signaling for bone modeling and remodeling. Crit Rev Eukaryot Gene Expr. 2009;19(4):319-338.
2013	Li S, Demirci E, Silberschmidt VV. Variability and anisotropy of mechanical behavior of cortical bone in tension and compression. J Mech Behav Biomed Mater. May 2013;21:109-120.
1987	Frost HM. Bone “mass” and the “mechanostat”: a proposal. Anat Rec. September 1987;219(1):1-9.
2018	Kersh ME, Martelli S, Zebaze R, Seeman E, Pandy MG. Mechanical loading of the femoral neck in human locomotion. J Bone Miner Res. November 2018;33(11):1999-2006.
2007	Wallace JM, Rajachar RM, Allen MR, Bloomfield SA, Robey PG, Young MF, Kohn DH. Exercise-induced changes in the cortical bone of growing mice are bone- and gender-specific. Bone. April 2007;40(4):1120-1127.
2004	Han Y, Cowin SC, Schaffler MB, Weinbaum S. Mechanotransduction and strain amplification in osteocyte cell processes. Proc Natl Acad Sci USA. November 23, 2004;101(47):16689-16694.
1983	Biewener AA, Thomason J, Goodship A, Lanyon LE. Bone stress in the horse forelimb during locomotion at different gaits: a comparison of two experimental methods. J Biomech. 1983;16(8):565-576.

Year

Entry

2013

Weatherholt AM, Fuchs RK, Warden SJ. Cortical and trabecular bone adaptation to incremental load magnitudes using the mouse tibial axial compression loading model. Bone. January 2013;52(1):372-379.

1993

Riggs CM, Lanyon LE, Boyde A. Functional associations between collagen fibre orientation and locomotor strain direction in cortical bone of the equine radius. Anat Embryol. March 1993;187(3):231-238.

1979

Lanyon LE, Magee PT, Baggott DG. The relationship of functional stress and strain to the processes of bone remodelling: an experimental study on the sheep radius. J Biomech. 1979;12(8):593-600.

1976

Lanyon LE, Baggott DG. Mechanical function as an influence on the structure and form of bone. J Bone Joint Surg. November 1976;58B(4):436-443.

2015

Zimmermann EA, Busse B, Ritchie RO. The fracture mechanics of human bone: influence of disease and treatment. BoneKEy Rep. September 2015;4:743.