Effects of tissue age on bone tissue material compositionand nanomechanical properties in the rat cortex

wbldb

Donnelly, Eve¹; Boskey, Adele L.^2,3,4; Baker, Shefford P.⁵; van der Meulen, Marjolein C. H.^1,2

Effects of tissue age on bone tissue material compositionand nanomechanical properties in the rat cortex

J Biomed Mater Res. March 1, 2010;A92(3):1048-1056

©2009 Wiley Periodicals, Inc.

Affiliations

¹Sibley School of Mechanical and Aerospace Engineering, Cornell University, Ithaca, New York

²Musculoskeletal Integrity Program, Hospital for Special Surgery, New York, New York

³Department of Biochemistry, Weill Medical College of Cornell University, New York, New York

⁴Graduate Program in Physiology, Biophysics, and Systems Biology, Weill Medical College of Cornell University, New York, New York

⁵Department of Materials Science and Engineering, Cornell University, Ithaca, New York
Abstract and keywords

Although osteoporosis is known to alter bone tissue composition, the effects of such compositional changes On tissue material properties have not yet been examined. The natural gradient in tissue mineral content arising from skeletal appositional growth provides a basic model for investigation of relationships between tissue composition and mechanical properties. The purpose of this study was to examine the effects of tissue age on bone tissue composition and nanomechanical properties. The nanomechanical properties and composition of regions of differing tissue age were characterized in the femoral cortices of growing rats using nanoindentation and Raman spectroscopy. In addition, spatial maps of the properties of periosteal tissue were examined to investigate in detail the spatial gradients in the properties of newly formed tissue. Newly formed tissue (0-4, days) was 84% less stiff and had 79% lower mineral:matrix ratio than older intracortical (15-70 days) tissue. Tissue modulus, hardness, mineral:matrix ratio, and carbonate:phosphate ratio increased sharply with distance from the periosteum and attained the properties of intracortical tissue within 4 days of formation. The mineral: matrix ratio explained 54% and 62%, of the variation in tissue indentation modulus and hardness, respectively. Our data demonstrate significant variations in tissue mechanical properties with tissue age and relate mechanical properties to composition at the microscale.

Keywords: bone mineralization; mechanical properties;nanoindentation; Raman spectroscopy; rat
Links

DOI: 0.1002/jbm.a.32442

PubMed: 19301272

WoS: 000274307600025
History

Received: 2008-02-20

Revised: 2008-09-26

Accepted: 2008-11-13

Online: 2009-03-19

Cited Works (35)

Year	Entry
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.
2003	Currey JD. Role of collagen and other organics in the mechanical properties of bone. Osteoporos Int. September 2003;14(suppl 5):S29-S36.
2006	Gupta HS, Stachewicz U, Wagermaier W, Roschger P, Wagner HD, Fratzl P. Mechanical modulation at the lamellar level in osteonal bone. J Mater Res. August 2006;21(8):1913-1921.
1995	Liberman UA, Weiss SR, Bröll J, Minne HW, Quan H, Bell NH, Rodriguez-Portales J, Downs RW Jr, Dequeker J, Favus M, Seeman E, Recker RR, Capizzi T, Santora AC, Lombardi A, Shah RV, Hirsch LJ, Karpf DB; Group, Alendronate Phase III Osteoporosis Treatment Study. Effect of oral alendronate on bone mineral density and the incidence of fractures in postmenopausal osteoporosis. NEJM. November 30, 1995;333(22):1437-1443.
1999	Ettinger B, Black DM, Mitlak BH, Knickerbocker RK, Nickelsen T, Genant HK, Christiansen C, Delmas PD, Zanchetta JR, Stakkestad J, Glüer CC, Krueger K, Cohen FJ, Eckert S, Ensrud KE, Avioli LV, Lips P, Cummings SR; Multiple Outcomes of Raloxifene Evaluation (MORE) Investigators. Reduction of vertebral fracture risk in postmenopausal women with osteoporosis treated with raloxifene: results from a 3-year randomized clinical trial. JAMA. August 18, 1999;282(7):637-645.
2006	Donnelly E, Williams RM, Downs SA, Dickinson ME, Baker SP, van der Meulen MCH. Quasistatic and dynamic nanomechanical properties of cancellous bone tissue relate to collagen content and organization. J Mater Res. August 2006;21(8):2106-2117.
2003	Roschger P, Gupta HS, Berzlanovich A, Ittner G, Dempster DW, Fratzl P, Cosman F, Parisien M, Lindsay R, Nieves JW, Klaushofer K. Constant mineralization density distribution in cancellous human bone. Bone. March 2003;32(3):316-323.
1969	Currey JD. The relationship between the stiffness and the mineral content of bone. J Biomech. October 1969;2(4):477-480.
2001	Laib A, Kumer JL, Majumdar S, Lane NE. The temporal changes of trabecular architecture in ovariectomized rats assessed by MicroCT. Osteoporos Int. November 2001;12(11):936-941.
2008	Roschger P, Paschalis EP, Fratzl P, Klaushofer K. Bone mineralization density distribution in health and disease. Bone. March 2008;42(3):456-466.
2006	Kazanci M, Roschger P, Paschalis EP, Klaushofer K, Fratzl P. Bone osteonal tissues by Raman spectral mapping: orientation–composition. J Struct Biol. December 2006;156(3):489-496.
2005	Boskey AL, Mendelsohn R. Infrared analysis of bone in health and disease. J Biomed Opt. May–June 2005;10(3):031102.
1998	Akiva U, Wagner HD, Weiner S. Modelling the three-dimensional elastic constants of parallel-fibred and lamellar bone. J Mater Sci. March 15, 1998;33(6):1497-1509.
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.
2002	Cummings SR, Melton LJ III. Epidemiology and outcomes of osteoporotic fractures. Lancet. May 18, 2002;359(9319):1761-1767.
1969	Currey JD. The mechanical consequences of variation in the mineral content of bone. J Biomech. March 1969;2(1):1-11.
2000	Guo XE, Goldstein SA. Vertebral trabecular bone microscopic tissue elastic modulus and hardness do not change in ovariectomized rats. J Orthop Res. March 2000;18(2):333-336.
2002	Cummings SR, Karpf DB, Harris F, Genant HK, Ensrud K, LaCroix AZ, Black DM. Improvement in spine bone density and reduction in risk of vertebral fractures during treatment with antiresorptive drugs. Am J Med. March 2002;112(4):281-289.
1988	Currey JD. The effect of porosity and mineral content on the Young's modulus of elasticity of compact bone. J Biomech. 1988;21(2):131-139.
2007	Miller LM, Little W, Schirmer A, Sheik F, Busa B, Judex S. Accretion of bone quantity and quality in the developing mouse skeleton. J Bone Miner Res. July 2007;22(7):1037-1045.
1999	Rho JY, Zioupos P, Currey JD, Pharr GM. Variations in the individual thick lamellar properties within osteons by nanoindentation. Bone. September 1999;25(3):295-300.
1999	Rho J-Y, Pharr GM. Effects of drying on the mechanical properties of bovine femur measured by nanoindentation. J Mater Sci Mater Med. 1999;10(8):485-488.
2002	Nuzzo S, Lafage‐Proust MH, Martin‐Badosa E, Boivin G, Thomas T, Alexandre C, Peyrin F. Synchrotron radiation microtomography allows the analysis of three‐dimensional microarchitecture and degree of mineralization of human iliac crest biopsy specimens: effects of etidronate treatment. J Bone Miner Res. August 2002;17(8):1372-1382.
2007	Tai K, Dao M, Suresh S, Palazoglu A, Ortiz C. Nanoscale heterogeneity promotes energy dissipation in bone. Nat Mater. June 2007;6(6):454-462.
1996	Ziv V, Wagner HD, Weiner S. Microstructure-microhardness relations in parallel-fibered and lamellar bone. Bone. May 1996;18(5):417-428.
2002	Hengsberger S, Kulik A, Zysset P. Nanoindentation discriminates the elastic properties of individual human bone lamellae under dry and physiological conditions. Bone. 2002;30(1):178-184.
2006	Lane NE, Yao W, Balooch M, Nalla RK, Balooch G, Habelitz S, Kinney JH, Bonewald LF. Glucocorticoid‐treated mice have localized changes in trabecular bone material properties and osteocyte lacunar size that are not observed in placebo‐treated or estrogen‐deficient mice. J Bone Miner Res. March 2006;21(3):466-476.
1992	Oliver WC, Pharr GM. An improved technique for determining hardness and elastic modulus using load and displacement sensing indentation experiments. J Mater Res. 1992;7(6):1564-1583.
2006	Donnelly E, Baker SP, Boskey AL, van der Meulen MC. Effects of surface roughness and maximum load on the mechanical properties of cancellous bone measured by nanoindentation. J Biomed Mater Res. May 2006;A77(2):426-435.
2002	Tarnowski CP, Ignelzi MA Jr, Morris MD. Mineralization of developing mouse calvaria as revealed by Raman microspectroscopy. J Bone Miner Res. June 2002;17(6):1118-1126.
1975	Burstein AH, Zika JM, Heiple KG, Klein L. Contribution of collagen and mineral to the elastic-plastic properties of bone. J Bone Joint Surg. October 1975;57A(7):956-961.
1992	Frost HM, Jee WSS. On the rat model of human osteopenias and osteoporoses. Bone Miner. September 1992;18(3):227-236.
1997	Paschalis EP, Betts F, DiCarlo E, Mendelsohn R, Boskey AL. FTIR microspectroscopic analysis of human iliac crest biopsies from untreated osteoporotic bone. Calcif Tiss Int. December 1997;61(6):487-492.
2004	Bushby AJ, Ferguson VL, Boyde A. Nanoindentation of bone: comparison of specimens tested in liquid and embedded in polymethylmethacrylate. J Bone Miner Res. January 2004;19(1):249-259.
2005	Busa B, Miller LM, Rubin CT, Qin Y-X, Judex S. Rapid establishment of chemical and mechanical properties during lamellar bone formation. Calcif Tiss Int. December 2005;77(6):386-394.

Cited By (55)

Year	Entry
2010	Isaksson H, Malkiewicz M, Nowak R, Helminen HJ, Jurvelin JS. Rabbit cortical bone tissue increases its elastic stiffness but becomes less viscoelastic with age. Bone. December 2010;47(6):1030-1038.
2013	Burket JC, Brooks DJ, MacLeay JM, Baker SP, Boskey AL, van der Meulen MCH. Variations in nanomechanical properties and tissue composition within trabeculae from an ovine model of osteoporosis and treatment. Bone. January 2013;52(1):326-336.
2020	Taylor EA, Donnelly E. Raman and Fourier transform infrared imaging for characterization of bone material properties. Bone. October 2020;139:115490.
2021	Vahidi G, Rux C, Sherk VD, Heveran CM. Lacunar-canalicular bone remodeling: impacts on bone quality and tools for assessment. Bone. February 2021;143:115663.
2021	Sherk VD, Heveran CM, Foright RM, Johnson GC, Presby DM, Ferguson VL, MacLean PS. Sex differences in the effect of diet, obesity, and exercise on bone quality and fracture toughness. Bone. April 2021;145:115840.
2022	Paschalis E, Gamsjaeger S, Burr D. Bone quality in an ovariectomized monkey animal model treated with two doses of teriparatide for either 18 months, or 12 months followed by withdrawal for 6 months. Bone. May 2022;158:116366.
2022	Gamsjaeger S, Rauch F, Glorieux FH, Paschalis EP. Cortical bone material / compositional properties in growing children and young adults aged 1.5–23 years, as a function of gender, age, metabolic activity, and growth spurt. Bone. December 2022;165:116548.
2015	Mandair GS, Morris MD. Contributions of Raman spectroscopy to the understanding of bone strength. BoneKEy Rep. January 7, 2015;4:620.
2010	Donnelly E, Chen DX, Boskey AL, Baker SP, van der Meulen MCH. Contribution of mineral to bone structural behavior and tissue mechanical properties. Calcif Tiss Int. November 2010;87(5):450-460.
2011	Morris MD, Mandair GS. Raman assessment of bone quality. Clin Orthop Relat Res. August 2011;469:2160-2169.
2011	Cole JH, van der Meulen MCH. Whole bone mechanics and bone quality. Clin Orthop Relat Res. August 2011;469(8):2139-2149.
2011	Burket J, Gourion-Arsiquaud S, Havill LM, Baker SP, Boskey AL, van der Meulen MCH. Microstructure and nanomechanical properties in osteons relate to tissue and animal age. J Biomech. January 11, 2011;44(2):277-284.
2011	Paietta RC, Campbell SE, Ferguson VL. Influences of spherical tip radius, contact depth, and contact area on nanoindentation properties of bone. J Biomech. January 2011;44(2):285-290.
2011	Bi X, Patil CA, Lynch CC, Pharr GM, Mahadevan-Jansen A, Nyman JS. Raman and mechanical properties correlate at whole bone- and tissue-levels in a genetic mouse model. J Biomech. January 11, 2011;44(2):297-303.
2012	Feng L, Chittenden M, Schirer J, Dickinson M, Jasiuk I. Mechanical properties of porcine femoral cortical bone measured by nanoindentation. J Biomech. June 26, 2012;45(10):1775-1782.
2019	Grover K, Hu M, Lin L, Muir J, Qin Y-X. Functional disuse initiates medullary endosteal micro-architectural impairment in cortical bone characterized by nanoindentation. J Bone Min Metab. November 2019;37(6):1048-1057.
2020	Törnquist E, Isaksson H, Turunen MJ. Mineralization of cortical bone during maturation and growth in rabbits. J Bone Min Metab. May 2020;38(3):289-298.
2016	Boskey AL, Donnelly E, Boskey E, Spevak L, Ma Y, Zhang W, Lappe J, Recker RR. Examining the relationships between bone tissue composition, compositional heterogeneity, and fragility fracture: a matched case-controlled FTIRI study. J Bone Miner Res. May 2016;31(5):1070-1081.
2021	Hunt HB, Miller NA, Hemmerling KJ, Koga M, Lopez KA, Taylor EA, Sellmeyer DE, Moseley KF, Donnelly E. Bone tissue composition in postmenopausal women varies with glycemic control from normal glucose tolerance to type 2 diabetes mellitus. J Bone Miner Res. February 2021;36(2):334-346.
2022	Damrath JG, Moe SM, Wallace JM. Calcimimetics alter periosteal and perilacunar bone matrix composition and material properties in early chronic kidney disease. J Bone Miner Res. July 2022;37(7):1297-1306.
2022	Dixit M, Louis LD, Basta-Pljakic J, Yildirim G, Poudel S-B, Kumararaja F, List EO, Duran SO, Kopchick JJ, Ruff RR, Schaffler MB, Yakar S. Lifelong excess in gh elicits sexually dimorphic effects on skeletal morphology and bone mechanical properties. J Bone Miner Res. November 2022;37(11):2201-2214.
2023	Lekkala S, Sacher SE, Taylor EA, Williams RM, Moseley KF, Donnelly E. Increased advanced glycation endproducts, stiffness, and hardness in iliac crest bone from postmenopausal women with type 2 diabetes mellitus on insulin. J Bone Miner Res. February 2023;38(2):261-277.
2012	Pathak S, Vachhani SJ, Jepsen KJ, Goldman HM, Kalidindi SR. Assessment of lamellar level properties in mouse bone utilizing a novel spherical nanoindentation data analysis method. J Mech Behav Biomed Mater. September 2012;13:102-117.
2015	Chittenden M, Najafi AR, Li J, Jasiuk I. Nanoindentation and ash content study of age dependent changes in porcine cortical bone. J Mech Med Biol. October 2015;15(5):1550074.
2017	Paschalis EP, Gamsjaeger S, Klaushofer K. Vibrational spectroscopic techniques to assess bone quality. Osteoporos Int. August 2017;28(8):2275-2291.
2018	Imbert L, Gourion-Arsiquaud S, Villarreal-Ramirez E, Spevak L, Taleb H, van der Meulen MCH, Mendelsohn R, Boskey AL. Dynamic structure and composition of bone investigated by nanoscale infrared spectroscopy. PLoS One. September 4, 2018;11(9):e0202833.
2017	Akbas AS. Local Bone Tissue Mechanical Property Changes Without Bone Remodeling: Regulation At the Osteocyte Level [PhD thesis]. New York, NY: The City College of New York; 2017.
2020	Mehraban Alvandi L. Diffuse Damage Repair Mechanism in Bone [PhD thesis]. New York, NY: The City College of New York; 2020.
2013	Paietta RC. Microscale Material Properties of Bone and the Mineralized Tissues of the Intervertebral Disc-Vertebral Body Interface [PhD thesis]. Boulder, CO: University of Colorado; 2013.
2017	Heveran CM. Bone Tissue Material Properties Are Altered in Chronic Kidney Disease to Lower Fracture Resistance Determining Bone Quality [PhD thesis]. University of Colorado; 2017.
2017	Yu Y. Contributions of Anisotropic and Heterogeneous Tissue Modulus to Apparent Trabecular Bone Mechanical Properties [PhD thesis]. New York, NY: Columbia University; 2017.
2013	Burket JC. Alterations in Tissue Composition and Nanomechanical Properties With Ageing, Osteoporosis, and Treatment [PhD thesis]. Ithaca, NY: Cornell University; January 2013.
2013	Kim G. The Effects of Mineralization and Crystallinity on the Mechanical Behavior of Bone [PhD thesis]. Ithaca, NY: Cornell University; May 2013.
2018	Chen JTH. Alterations in Bone Tissue Properties With Parathyroid Hormone Treatment [PhD thesis]. Ithaca, NY: Cornell University; May 2018.
2018	Guss JD. The Role of the Gut Microbiome in Bone and Joint [PhD thesis]. Ithaca, NY: Cornell University; December 2018.
2020	Luna M. The Influence of the Gut Microbiome on Bone and Joint Disease [PhD thesis]. Ithaca, NY: Cornell University; August 2020.
2020	Taylor EA. Validation and Implementation of Vibrational Spectroscopic Measures of Bone Composition [PhD thesis]. Ithaca, NY: Cornell University; December 2020.
2023	Maghami E. Fracture Micromechanics Analyses of Hard Tissues: Study of Increased Glycation Through Diabetes and Age-Related Changes [PhD thesis]. Drexel University; January 2023.
2011	Wu Z. Measures of Bone Quality and Their Relationship to Bone Mechanical Properties [PhD thesis]. University of Notre Dame; December 2011.
2018	Johnson TB. Effect of Guided Bone Regeneration With RhBMP-2 on Bone Quality Surrounding Dental Implants [Master's thesis]. The Ohio State University; 2018.
2010	Gurkan UA. Engineering of Bone Marrow in Vitro for Investigating the Role of Growth Factors and Their Mechanoresponsiveness in Osteogenesis [PhD thesis]. Purdue University; May 2010.
2019	Beltejar M-JG. Understanding the Genetic Basis for Bone-Matrix Quality [PhD thesis]. University of Rochester; 2019.
2010	Edwards L. Assessment of Bone Mineralization in Rats Treated With Sclerostin Antibody [Master's thesis]. Rush University; 2010.
2015	Grover K. Osteopenia Uncovered by Remodeling in Spatial Distribution of Elastic Moduli in Orthogonal Orientations: A Nanoindentation Study [Master's thesis]. Stony Brook, NY: Stony Brook University; May 2015.
2013	Wu Y. Compositional and Material Properties of Rat Bone After Drug Treatment [PhD thesis]. Edmonton, AB: University of Alberta; 2013.
2011	Raghavan M. Investigation of Mineral and Collagen Organization in Bone Using Raman Spectroscopy [PhD thesis]. University of Michigan; 2011.
2012	McElderry J-DP. Dynamics of Mineralization During Bone Development [PhD thesis]. University of Michigan; 2012.
2014	Sinder BP. Sclerostin Antibody as a Treatment for Osteogenesis Imperfecta [PhD thesis]. University of Michigan; 2014.
2016	Vrahna C. Investigating the Effects of Downstream Parathyroid Hormone (PTH) Targets on Bone Strength and Quality [PhD thesis]. Melbourne, Australia: The University of Melbourne; December 2016.
2022	Blank MA. Defining Mechanisms by Which EphrinB2 in Osteocytes Controls Bone Strength and Material Quality [PhD thesis]. University of Melbourne; September 2022.
2015	Lin C-L. A Study of Human and Bovine Trabecular Bones Using Nanoindentation and Quantitative Backscattered Electron Imaging [PhD thesis]. Brisbane, Australia: University of Queensland; 2015.
2020	Singleton RC. A Study of Aging in Male Cortical Bone Using Nanoindentation [PhD thesis]. Knoxville, University of Tennessee; August 2020.
2015	Ng AH-M. A Mouse Model of Adynamic Bone Disease (ABD) and Its Consequences on Bone Quality With Age [PhD thesis]. University of Toronto; 2015.
2014	Makowski AJ. Evaluation of Raman Spectroscopy for Fracture Resistance Assessment [PhD thesis]. Nashville, TN: Vanderbilt University; December 2014.
2014	Schwartz AG. Ihh Signaling and Muscle Forces Are Required for Enthesis Development [PhD thesis]. St. Louis, MO: Washington University in St. Louis; May 2014.