Biomechanical Origins of Osteoporosis

The contention of this thesis is that a pathological change in bone tissue material properties during osteoporosis ahers the mechanical stimuli to bone remodelling cells and drives them to adapt the trabecular architecture resulting in a reduction in bone strength. To argue the case for this thesis, three separate but inter-related hypotheses with respect to the regulatory mechanisms governing bone remodelling are tested. These hypotheses are (1) A pathological change in the material properties of bone tissue occurs during osteoporosis, (2) Bone remodelling is regulated by a combination of strain and damage, and (3) Suppressing bone turnover in drug treated bone results in weaker bone tissue than that of normal and osteoporotic bone.

A method to evaluate mechanical behaviour of single bone trabeculae is developed to assess the mechanical properties of normal, osteoporotic and drug treated bone tissue. A micro-tensile testing apparatus is developed that minimizes errors due to misalignment and stress concentrations at the grips. The method is used to test the hypothesis that the strength of single trabeculae will differ for normal, ovarectomized, and drug treated rat bones over the course of ageing (hypotheses 1 and 3).

A method of producing accurate solid models of individual trabeculae, through the use of serial sectioning at micro resolutions and micro-CT scanning, is developed. These models are used to analyse the stress distribution within trabeculae and the effects of the presence of resorption lacunae on these distributions in order to determine whether the structure of the individual trabecula may be maintained by strain or by the presence of microdamage, or a combination of both (hypothesis 2).

A mechano-regulation rule for bone remodelling is developed that relates the mechanical stimuli to the change in bone mass. This rule is applied to a computational model of a bone trabecula to predict bone remodelling along trabecular surfaces. These simulations reveal the regulatory mechanisms that govern initiation, propagation and termination of the normal bone remodelling process (hypothesis 2).

Finally, this rule is applied to models with material properties of osteoporotic bone tissue to investigate the main contention of this thesis.

Year	Entry
1990	Beaupré GS, Orr TE, Carter DR. An approach for time‐dependent bone modeling and remodeling: theoretical development. J Orthop Res. September 1990;8(5):651-661.
2000	Boivin GY, Chavassieux PM, Santora AC, Yates J, Meunier PJ. Alendronate increases bone strength by increasing the mean degree of mineralization of bone tissue in osteoporotic women. Bone. November 2000;27(5):687-694.
2002	Currey JD. Bones: Structure and Mechanics. Princeton, NJ: Princeton University Press; 2002.
1997	Keaveny TM, Pinilla TP, Crawford RP, Kopperdahl DL, Lou A. Systematic and random errors in compression testing of trabecular bone [published correction appears in J Orthop Res. 1995;17(1):151]. J Orthop Res. 1997;15(1):101-110.
1952	Dempster WT, Liddicoat RT. Compact bone as a non-isotropic material. Am J Anat. 1952;91(3):331-362.
1975	Townsend PR, Rose RM, Radin EL. Buckling studies of single human trabeculae. J Biomech. July 1975;8(3-4):199-200.
2001	Keaveny TM. Strength of trabecular bone. In: Cowin SC, ed. Bone Mechanics Handbook. 2nd ed. Boca Raton, FL: CRC Press; 2001:16-1–16-42.
1997	Meunier PJ, Boivin G. Bone mineral density reflects bone mass but also the degree of mineralization of bone: therapeutic implications. Bone. November 1997;21(5):373-377.
1996	Prendergast PJ, Huiskes R. Microdamage and osteocyte-lacuna strain in bone: a microstructural finite element analysis. J Biomech Eng. May 1996;118(2):240-246.
1994	Prendergast P, Taylor D. Prediction of bone adaptation using damage accumulation. J Biomech. August 1994;27(8):1067-1076.
1993	Boyde A, Elliott JC, Jones SJ. Stereology and histogram analysis of backscattered electron images: age changes in bone. Bone. May–June 1993;14(3):205-210.
1976	Carter DR, Hayes WC, Schurman DJ. Fatigue life of compact bone, II: effects of microstructure and density. J Biomech. 1976;9(4):211-218.
1988	Harrigan TP, Jasty M, Mann RW, Harris WH. Limitations of the continuum assumption in cancellous bone. J Biomech. 1988;21(4):269-275.
1989	Mente PL, Lewis JL. Experimental method for the measurement of the elastic modulus of trabecular bone tissue. J Orthop Res. 1989;7(3):456-461.
1996	Wenzel TE, Schaffler MB, Fyhrie DP. In vivo trabecular microcracks in human vertebral bone. Bone. August 1996;19(2):89-95.
2003	Burger EH, Klein-Nulend J, Smit TH. Strain-derived canalicular fluid flow regulates osteoclast activity in a remodelling osteon: a proposal. J Biomech. October 2003;36(10):1453-1459.
2000	Smit TH, Burger EH. Is BMU-coupling a strain-regulated phenomenon? a finite element analysis. J Bone Miner Res. February 2000;12(2):301-307.
2002	Smit TH, Huyghe JM, Cowin SC. Estimation of the poroelastic parameters of cortical bone. J Biomech. June 2002;35(6):829-835.
2001	Lucchinetti E. Dense bone tissue as a molecular composite. In: Cowin SC, ed. Bone Mechanics Handbook. 2nd ed. Boca Raton, FL: CRC Press; 2001:13-1–13-15.
1994	Weinbaum S, Cowin SC, Zeng Y. A model for the excitation of osteocytes by mechanical loading-induced bone fluid shear stresses. J Biomech. March 1994;27(3):339-360.
1989	Martin RB, Burr DB. Structure, Function, and Adaptation of Compact Bone. New York, NY: Raven Press; 1989.
2001	Jee WSS. Integrated bone tissue physiology: anatomy and physiology. In: Cowin SC, ed. Bone Mechanics Handbook. 2nd ed. Boca Raton, FL: CRC Press; 2001:1-1–1-68.
1997	Odgaard A. Three-dimensional methods for quantification of cancellous bone architecture. Bone. 1997;20(4):315-328.
1990	Beaupré GS, Orr TE, Carter DR. An approach for time‐dependent bone modeling and remodeling—application: a preliminary remodeling simulation. J Orthop Res. September 1990;8(5):662-670.
1999	Burger EH, Klein-Nulend J. Mechanotransduction in bone: role of the lacunocanalicular network. FASEB J. May 1999;12(9001):S101-S112.
2000	Hirano T, Turner CH, Forwood MR, Johnston CC, Burr DB. Does suppression of bone turnover impair mechanical properties by allowing microdamage accumulation? Bone. July 2000;27(1):13-20.
1993	Recker RR. Architecture and vertebral fracture. Calcif Tiss Int. 1993;53(suppl 1):S139-S142.
1994	Mullender MG, Huiskes R, Weinans H. A physiological approach to the simulation of bone remodeling as a self-organizational control process. J Biomech. November 1994;27(11):1389-1394.
1989	Ryan SD, Williams JL. Tensile testing of rodlike trabeculae excised from bovine femoral bone. J Biomech. 1989;22(4):351-355.
1997	Mullender MG, Huiskes R. Osteocytes and bone lining cells: which are the best candidates for mechano-sensors in cancellous bone? Bone. June 1997;20(6):527-532.
1993	Lanyon LE. Osteocytes, strain detection, bone modeling and remodeling. Calcif Tiss Int. February 1993;53(suppl 1):S102-S107.
1993	Goldstein SA, Goulet R, McCubbrey D. Measurement and significance of three-dimensional architecture to the mechanical integrity of trabecular bone. Calcif Tiss Int. February 1993;53(suppl 1):S127-S133.
1996	Parfitt AM, Mundy GR, Roodman GD, Hughes DE, Boyce BF. A new model for the regulation of bone resorption, with particular reference to the effects of bisphosphonates. J Bone Miner Res. February 1996;11(2):150-159.
2001	van der Linden JC, Homminga J, Verhaar JAN, Weinans H. Mechanical consequences of bone loss in cancellous bone. J Bone Miner Res. March 2001;16(3):457-465.
1981	Carter DR, Caler WE, Spengler DM, Frankel VH. Uniaxial fatigue of human cortical bone: the influence of tissue physical characteristics. J Biomech. 1981;14(7):461-470.
1993	Mori S, Burr DB. Increased intracortical remodeling following fatigue damage. Bone. March–April 1993;14(2):103-109.
1997	Mori S, Harruff R, Ambrosius W, Burr DB. Trabecular bone volume and microdamage accumulation in the femoral heads of women with and without femoral neck fractures. Bone. December 1997;21(6):521-526.
1998	Martin RB, Burr DB, Sharkey NA. Skeletal Tissue Mechanics. New York, NY: Springer-Verlag; 1998.
1989	Kuhn JL, Goldstein SA, Choi K, London M, Feldkamp LA, Matthews LS. Comparison of the trabecular and cortical tissue moduli from human iliac crests. J Orthop Res. November 1989;7(6):876-884.
1998	Ulrich D, van Rietbergen B, Weinans H, Rüegsegger P. Finite element analysis of trabecular bone structure: a comparison of image-based meshing techniques. J Biomech. December 1998;31(12):1187-1192.
1989	Hodgskinson R, Currey JD, Evans GP. Hardness, an indicator of the mechanical competence of cancellous bone. J Orthop Res. September 1989;7(5):754-758.
1994	Guo X-DE, McMahon TA, Keaveny TM, Hayes WC, Gibson LJ. Finite element modeling of damage accumulation in trabecular bone under cyclic loading. J Biomech. February 1994;27(2):145-155.
1999	Cowin SC. Bone poroelasticity. J Biomech. March 1999;32(3):217-238.
1989	Carter DR, Orr TE, Fyhrie DP. Relationships between loading history and femoral cancellous bone architecture. J Biomech. 1989;22(3):231-244.
1981	Carter DR, Caler WE, Spengler DM, Frankel VH. Fatigue behavior of adult cortical bone: the influence of mean strain and strain range. Acta Orthop Scand. 1981;52(5):481-490.
1999	Sugita H, Oka M, Toguchida J, Nakamura T, Ueo T, Hayami T. Anisotropy of osteoporotic cancellous bone. Bone. May 1999;24(5):513-516.
1987	Carter DR, Fyhrie DP, Whalen RT. Trabecular bone density and loading history: regulation of connective tissue biology by mechanical energy. J Biomech. 1987;20(8):785-794.
1984	Currey JD. Effects of differences in mineralization on the mechanical properties of bone. Philos Trans R Soc Lond B Biol Sci. February 13, 1984;304(1121):509-518.
1984	Carter DR. Mechanical loading histories and cortical bone remodeling. Calcif Tiss Int. March 1984;36(suppl 1):S19-S24.
1992	Weinans H, Huiskes R, Grootenboer HJ. The behavior of adaptive bone-remodeling simulation models. J Biomech. December 1992;25(12):1425-1441.
2001	van der Linden JC, Birkenhäger-Frenkel DH, Verhaar JAN, Weinans H. Trabecular bone's mechanical properties are affected by its non-uniform mineral distribution. J Biomech. December 2001;34(12):1573-1580.
1985	Cummings SR, Kelsey JL, Nevitt MC, O'Dowd KJ. Epidemiology of osteoporosis and osteoporotic fractures. Epidemiol Rev. 1985;7:178-208.
1993	Linde F, Sørensen HCF. The effect of different storage methods on the mechanical properties of trabecular bone. J Biomech. 1993;26(10):1249-1252.
2000	Huiskes R, Ruimerman R, van Lenthe GH, Janssen JD. Effects of mechanical forces on maintenance and adaptation of form in trabecular bone. Nature. June 8, 2000;405(6787):704-706.
1986	Dempster DW, Shane E, Horbert W, Lindsay R. A simple method for correlative light and scanning electron microscopy of human iliac crest bone biopsies: qualitative observations in normal and osteoporotic subjects. J Bone Miner Res. February 1986;1(1):15-21.
1998	Rho J-Y, Kuhn-Spearing L, Zioupos P. Mechanical properties and the hierarchical structure of bone. Med Eng Phys. 1998;20(2):92-102.
1997	Nicholson PHF, Cheng XG, Lowet G, Boonen S, Davie MWJ, Dequeker J, Van der Perre G. Structural and material mechanical properties of human vertebral cancellous bone. Med Eng Phys. October 1997;19(8):729-737.
1997	Li B, Aspden R. Material properties of bone from the femoral neck and calcar femorale of patients with osteoporosis or osteoarthritis. Osteoporos Int. September 1997;7(5):450-456.
1960	Frost HM. Presence of microscopic cracks in vivo in bone. Henry Ford Hosp Med Bull. 1960;8(1):25-35.
2000	Vashishth D, Verborgt O, Divine G, Schaffler MB, Fyhrie DP. Decline in osteocyte lacunar density in human cortical bone is associated with accumulation of microcracks with age. Bone. April 2000;26(4):375-380.
2002	Cummings SR, Melton LJ III. Epidemiology and outcomes of osteoporotic fractures. Lancet. May 18, 2002;359(9319):1761-1767.
2002	Hu JH, Ding M, Søballe K, Bechtold JE, Danielsen CC, Day JS, Hvid I. Effects of short-term alendronate treatment on the three-dimensional microstructural, physical, and mechanical properties of dog trabecular bone. Bone. November 2002;31(5):591-597.
1991	Cowin SC, Moss-Salentijn L, Moss ML. Candidates for the mechanosensory system in bone. J Biomech Eng. May 1991;113(2):191-197.
1999	Huja SS, Hasan MS, Pidaparti R, Turner CH, Garetto LP, Burr DB. Development of a fluorescent light technique for evaluating microdamage in bone subjected to fatigue loading. J Biomech. November 1999;32(11):1243-1249.
1995	Cowin SC, Weinbaum S, Zeng Y. A case for bone canaliculi as the anatomical site of strain generated potentials. J Biomech. November 1995;28(11):1281-1297.
2000	Gadeleta SJ, Boskey AL, Paschalis E, Carlson C, Menschik F, Baldini T, Peterson M, Rimnac CM. A physical, chemical, and mechanical study of lumbar vertebrae from normal, ovariectomized, and nandrolone decanoate-treated cynomolgus monkeys (macaca fascicularis). Bone. October 2000;27(4):541-550.
2003	Homminga J, McCreadie BR, Weinans H, Huiskes R. The dependence of the elastic properties of osteoporotic cancellous bone on volume fraction and fabric. J Biomech. October 2003;36(10):1461-1467.
1993	Michel MC, Guo X-DE, Gibson LJ, McMahon TA, Hayes WC. Compressive fatigue behavior of bovine trabecular bone. J Biomech. April–May 1993;26(4-5):453-463.
2000	O’Brien FJ, Taylor D, Dickson GR, Lee TC. Visualisation of three‐dimensional microcracks in compact bone. J Anat. October 2000;197(3):413-420.
2004	Homminga J, Van-Rietbergen B, Lochmüller EM, Weinans H, Eckstein F, Huiskes R. The osteoporotic vertebral structure is well adapted to the loads of daily life, but not to infrequent “error” loads. Bone. March 2004;34(3):510-516.
1994	Keaveny TM, Wachtel EF, Ford CM, Hayes WC. Differences between the tensile and compressive strengths of bovine tibial trabecular bone depend on modulus. J Biomech. 1994;27(9):1137-1146.
1976	Cowin SC, Hegedus DH. Bone remodeling, I: theory of adaptive elasticity. J Elast. 1976;6(3):313-326.
1992	Choi K, Goldstein SA. A comparison of the fatigue behavior of human trabecular and cortical bone tissue. J Biomech. 1992;25(12):1371-1381.
1979	Cowin SC, Van Buskirk WC. Surface bone remodeling induced by a medullary pin. J Biomech. 1979;12(4):269-276.
2000	Verborgt O, Gibson GJ, Schaffler MB. Loss of osteocyte integrity in association with microdamage and bone remodeling after fatigue in vivo. J Bone Miner Res. January 2000;15(1):60-67.
1989	Compston JE, Mellish RWE, Croucher P, Newcombe R, Garrahan NJ. Structural mechanisms of trabecular bone loss in man. Bone Miner. July 1989;6(3):339-350.
2002	Ito M, Nishida A, Nakamura T, Uetani M, Hayashi K. Differences of three-dimensional trabecular microstructure in osteopenic rat models caused by ovariectomy and neurectomy. Bone. April 2002;30(4):594-598.
1995	van Rietbergen B, Weinans H, Huiskes R, Odgaard A. A new method to determine trabecular bone elastic properties and loading using micromechanical finite-element models. J Biomech. January 1995;28(1):69-81.
2000	Reilly GC. Observations of microdamage around osteocyte lacunae in bone. J Biomech. September 2000;33(9):1131-1134.
1999	Van Rietbergen B, Müller R, Ulrich D, Rüegsegger P, Huiskes R. Tissue stresses and strain in trabeculae of a canine proximal femur can be quantified from computer reconstructions. J Biomech. February 1999;32(2):165-173.
1997	Rho J-Y, Tsui TY, Pharr GM. Elastic properties of human cortical and trabecular lamellar bone measured by nanoindentation. Biomaterials. 1997;18(20):1325-1330.
2000	Vashishth D, Koontz J, Qiu SJ, Lundin-Cannon D, Yeni YN, Schaffler MB, Fyhrie DP. In vivo diffuse damage in human vertebral trabecular bone. Bone. February 2000;26(2):147-152.
1987	Huiskes R, Weinans H, Grootenboer HJ, Dalstra M, Fudala B, Slooff TJ. Adaptive bone-remodeling theory applied to prosthetic-design analysis. J Biomech. 1987;20(11-12):1135-1150.
1999	Kothari M, Keaveny TM, Lin JC, Newitt DC, Majumdar S. Measurement of intraspecimen variations in vertebral cancellous bone architecture. Bone. August 1999;25(2):245-250.
1993	Rho JY, Ashman RB, Turner CH. Young's modulus of trabecular and cortical bone material: ultrasonic and microtensile measurements. J Biomech. February 1993;26(2):111-119.
1994	Currey JD, Brear K, Zioupos P. Dependence of mechanical properties on fibre angle in narwhal tusk, a highly oriented biological composite. J Biomech. July 1994;27(7):885-897.
2000	Lee TC, Arthur TL, Gibson LJ, Hayes WC. Sequential labelling of microdamage in bone using chelating agents. J Orthop Res. March 2000;18(2):322-325.
2000	Lee TC, O'Brien FJ, Taylor D. The nature of fatigue damage in bone. Int J Fract. November 2000;22(10):847-853.
1998	Burr DB, Turner CH, Naick P, Forwood MR, Ambrosius W, Hasan MS, Pidaparti R. Does microdamage accumulation affect the mechanical properties of bone? J Biomech. April 1998;31(4):337-345.
1993	Keaveny TM, Borchers RE, Gibson L, Hayes WC. Trabecular bone modulus and strength can depend on specimen geometry. J Biomech. August 1993;26(8):991-995.
1990	Choi K, Kuhn JL, Ciarelli MJ, Goldstein SA. The elastic moduli of human subchondral, trabecular, and cortical bone tissue and the size-dependency of cortical bone modulus. J Biomech. 1990;23(11):1103-1113.
1975	Runkle JC, Pugh J. The micro-mechanics of cancellous bone, II: determination of the elastic modulus of individual trabeculae by a buckling analysis. Bull Hosp Joint Dis. April 1975;36(1):2-10.
1984	Parfitt AM. The cellular basis of bone remodeling: the quantum concept reexamined in light of recent advances in the cell biology of bone. Calcif Tiss Int. March 1984;36(suppl 1):S37-S45.
1999	Turner CH, Rho J, Takano Y, Tsui TY, Pharr GM. The elastic properties of trabecular and cortical bone tissues are similar: results from two microscopic measurement techniques. J Biomech. April 1999;32(4):437-441.
1990	Fyhrie DP, Carter DR. Femoral head apparent density distribution predicted from bone stresses. J Biomech. 1990;23(1):1-10.
2002	Martin RB. Is all cortical bone remodeling initiated by microdamage? Bone. January 2002;30(1):8-13.
1998	Kopperdahl DL, Keaveny TM. Yield strain behavior of trabecular bone. J Biomech. July 1998;31(7):601-608.
1993	Huiskes R, Hollister SJ. From structure to process, from organ to cell: recent developments of FE-analysis in orthopaedic biomechanics. J Biomech Eng. November 1993;115(4B):520-527.
1985	Burr DB, Martin RB, Schaffler MB, Radin EL. Bone remodeling in response to in vivo fatigue microdamage. J Biomech. 1985;18(3):189-200.
2004	Waarsing JH, Day JS, van der Linden JC, Ederveen AG, Spanjers C, De Clerck N, Sasov A, Verhaar JAN, Weinans H. Detecting and tracking local changes in the tibiae of individual rats: a novel method to analyse longitudinal in vivo micro-ct data. Bone. January 2004;34(1):163-169.
1996	Pidaparti RMV, Chandran A, Takano Y, Turner CH. Bone mineral lies mainly outside collagen fibrils: predictions of a composite model for osternal bone. J Biomech. July 1996;29(7):909-916.
1986	Frost HM. Intermediary Organization of the Skeleton. Vols. 1-2. Boca Raton, FL: CRC Press; 1986.
1991	Cohen‐Solal ME, Shih M, Lundy MW, Parfitt AM. A new method for measuring cancellous bone erosion depth: application to the cellular mechanisms of bone loss in postmenopausal osteoporosis. J Bone Miner Res. December 1991;6(12):1331-1338.
1998	Lane NE, Thompson JM, Haupt D, Kimmel DB, Modin G, Kinney JH. Acute changes in trabecular bone connectivity and osteoclast activity in the ovariectomized rat in vivo. J Bone Miner Res. February 1998;13(2):229-236.
1980	Gottesman T, Hashin Z. Analysis of viscoelastic behaviour of bones on the basis of microstructure. J Biomech. 1980;13(2):89-96.
1986	Wolff J. The Law of Bone Remodelling. Maquet P, Furlong R, trans. New York, NY: Springer; 1986.
1998	Boyde A, Compston JE, Reeve J, Bell KL, Noble BS, Jones SJ, Loveridge N. Effect of estrogen suppression on the mineralization density of iliac crest biopsies in young women as assessed by backscattered electron imaging. Bone. March 1998;22(3):241-250.
1981	Dickenson RP, Hutton WC, Stott JRR. The mechanical properties of bone in osteoporosis. J Bone Joint Surg. August 1981;63B(2):233-238.
2001	Hart RT. Bone modeling and remodeling: theories and computation. In: Cowin SC, ed. Bone Mechanics Handbook. 2nd ed. Boca Raton, FL: CRC Press; 2001:31-1–31-42.
2000	Lucchinetti E, Thomann D, Danuser G. Micromechanical testing of bone trabeculae: potentials and limitations. J Mater Sci. December 2000;35(24):6057-6064.
2000	Lee TC, Staines A, Taylor D. Bone adaptation to load: microdamage as a stimulus for bone remodelling. J Anat. December 2000;201(6):437-446.

Year

Entry

1990

Beaupré GS, Orr TE, Carter DR. An approach for time‐dependent bone modeling and remodeling: theoretical development. J Orthop Res. September 1990;8(5):651-661.

2000

Boivin GY, Chavassieux PM, Santora AC, Yates J, Meunier PJ. Alendronate increases bone strength by increasing the mean degree of mineralization of bone tissue in osteoporotic women. Bone. November 2000;27(5):687-694.

2002

Currey JD. Bones: Structure and Mechanics. Princeton, NJ: Princeton University Press; 2002.

1997

Keaveny TM, Pinilla TP, Crawford RP, Kopperdahl DL, Lou A. Systematic and random errors in compression testing of trabecular bone [published correction appears in J Orthop Res. 1995;17(1):151]. J Orthop Res. 1997;15(1):101-110.

1952

Dempster WT, Liddicoat RT. Compact bone as a non-isotropic material. Am J Anat. 1952;91(3):331-362.

1975

Townsend PR, Rose RM, Radin EL. Buckling studies of single human trabeculae. J Biomech. July 1975;8(3-4):199-200.

2001

Keaveny TM. Strength of trabecular bone. In: Cowin SC, ed. Bone Mechanics Handbook. 2nd ed. Boca Raton, FL: CRC Press; 2001:16-1–16-42.

1997

Meunier PJ, Boivin G. Bone mineral density reflects bone mass but also the degree of mineralization of bone: therapeutic implications. Bone. November 1997;21(5):373-377.

1996

Prendergast PJ, Huiskes R. Microdamage and osteocyte-lacuna strain in bone: a microstructural finite element analysis. J Biomech Eng. May 1996;118(2):240-246.

1994

Prendergast P, Taylor D. Prediction of bone adaptation using damage accumulation. J Biomech. August 1994;27(8):1067-1076.

1993

Boyde A, Elliott JC, Jones SJ. Stereology and histogram analysis of backscattered electron images: age changes in bone. Bone. May–June 1993;14(3):205-210.

1976

Carter DR, Hayes WC, Schurman DJ. Fatigue life of compact bone, II: effects of microstructure and density. J Biomech. 1976;9(4):211-218.

1988

Harrigan TP, Jasty M, Mann RW, Harris WH. Limitations of the continuum assumption in cancellous bone. J Biomech. 1988;21(4):269-275.

1989

Mente PL, Lewis JL. Experimental method for the measurement of the elastic modulus of trabecular bone tissue. J Orthop Res. 1989;7(3):456-461.

1996

Wenzel TE, Schaffler MB, Fyhrie DP. In vivo trabecular microcracks in human vertebral bone. Bone. August 1996;19(2):89-95.

2003

Burger EH, Klein-Nulend J, Smit TH. Strain-derived canalicular fluid flow regulates osteoclast activity in a remodelling osteon: a proposal. J Biomech. October 2003;36(10):1453-1459.

2000

Smit TH, Burger EH. Is BMU-coupling a strain-regulated phenomenon? a finite element analysis. J Bone Miner Res. February 2000;12(2):301-307.

2002

Smit TH, Huyghe JM, Cowin SC. Estimation of the poroelastic parameters of cortical bone. J Biomech. June 2002;35(6):829-835.

2001

Lucchinetti E. Dense bone tissue as a molecular composite. In: Cowin SC, ed. Bone Mechanics Handbook. 2nd ed. Boca Raton, FL: CRC Press; 2001:13-1–13-15.

1994

Weinbaum S, Cowin SC, Zeng Y. A model for the excitation of osteocytes by mechanical loading-induced bone fluid shear stresses. J Biomech. March 1994;27(3):339-360.

1989

Martin RB, Burr DB. Structure, Function, and Adaptation of Compact Bone. New York, NY: Raven Press; 1989.

2001

Jee WSS. Integrated bone tissue physiology: anatomy and physiology. In: Cowin SC, ed. Bone Mechanics Handbook. 2nd ed. Boca Raton, FL: CRC Press; 2001:1-1–1-68.

1997

Odgaard A. Three-dimensional methods for quantification of cancellous bone architecture. Bone. 1997;20(4):315-328.

1990

Beaupré GS, Orr TE, Carter DR. An approach for time‐dependent bone modeling and remodeling—application: a preliminary remodeling simulation. J Orthop Res. September 1990;8(5):662-670.

1999

Burger EH, Klein-Nulend J. Mechanotransduction in bone: role of the lacunocanalicular network. FASEB J. May 1999;12(9001):S101-S112.

2000

Hirano T, Turner CH, Forwood MR, Johnston CC, Burr DB. Does suppression of bone turnover impair mechanical properties by allowing microdamage accumulation? Bone. July 2000;27(1):13-20.

1993

Recker RR. Architecture and vertebral fracture. Calcif Tiss Int. 1993;53(suppl 1):S139-S142.

1994

Mullender MG, Huiskes R, Weinans H. A physiological approach to the simulation of bone remodeling as a self-organizational control process. J Biomech. November 1994;27(11):1389-1394.

1989

Ryan SD, Williams JL. Tensile testing of rodlike trabeculae excised from bovine femoral bone. J Biomech. 1989;22(4):351-355.

1997

Mullender MG, Huiskes R. Osteocytes and bone lining cells: which are the best candidates for mechano-sensors in cancellous bone? Bone. June 1997;20(6):527-532.

1993

Lanyon LE. Osteocytes, strain detection, bone modeling and remodeling. Calcif Tiss Int. February 1993;53(suppl 1):S102-S107.

1993

Goldstein SA, Goulet R, McCubbrey D. Measurement and significance of three-dimensional architecture to the mechanical integrity of trabecular bone. Calcif Tiss Int. February 1993;53(suppl 1):S127-S133.

1996

Parfitt AM, Mundy GR, Roodman GD, Hughes DE, Boyce BF. A new model for the regulation of bone resorption, with particular reference to the effects of bisphosphonates. J Bone Miner Res. February 1996;11(2):150-159.

2001

van der Linden JC, Homminga J, Verhaar JAN, Weinans H. Mechanical consequences of bone loss in cancellous bone. J Bone Miner Res. March 2001;16(3):457-465.

1981

Carter DR, Caler WE, Spengler DM, Frankel VH. Uniaxial fatigue of human cortical bone: the influence of tissue physical characteristics. J Biomech. 1981;14(7):461-470.

1993

Mori S, Burr DB. Increased intracortical remodeling following fatigue damage. Bone. March–April 1993;14(2):103-109.

1997

Mori S, Harruff R, Ambrosius W, Burr DB. Trabecular bone volume and microdamage accumulation in the femoral heads of women with and without femoral neck fractures. Bone. December 1997;21(6):521-526.

1998

Martin RB, Burr DB, Sharkey NA. Skeletal Tissue Mechanics. New York, NY: Springer-Verlag; 1998.

1989

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Year	Entry
2007	Scannell PT. Mechanoregulation Algorithms Predicting Peri-Prosthetic Bone Adaptations [PhD thesis]. Trinity College Dublin; 2007.
2008	Mulvihill BMC. Computational Investigation Into the Mechanoregulation of Osteoporosis [PhD thesis]. Trinity College Dublin; December 2008.

Year

Entry

2007

Scannell PT. Mechanoregulation Algorithms Predicting Peri-Prosthetic Bone Adaptations [PhD thesis]. Trinity College Dublin; 2007.

2008

Mulvihill BMC. Computational Investigation Into the Mechanoregulation of Osteoporosis [PhD thesis]. Trinity College Dublin; December 2008.