The role of matrix composition in the mechanical behavior of bone

wbldb

Unal, Mustafa^1,2,3; Creecy, Amy^1,2,4; Nyman, Jeffry S.^1,2,3,4,5

The role of matrix composition in the mechanical behavior of bone

Curr Osteoporos Rep. June 2018;16(3):205-215

©2018 Springer Science+Business Media, LLC, part of Springer Nature

Affiliations

¹Department of Orthopaedic Surgery & Rehabilitation, Vanderbilt University Medical Center, Nashville, TN 37232, USA

²Center for Bone Biology, Vanderbilt University Medical Center, Nashville, TN 37232, USA

³Vanderbilt Biophotonics Center, Vanderbilt University, Nashville, TN 37232, USA

⁴Department of Biomedical Engineering, Vanderbilt University, Nashville, TN 37232, USA

⁵Vanderbilt Orthopedic Institute, Medical Center East, South Tower, Suite 4200, Nashville, TN 37232, USA
Abstract and keywords

Purpose of Review: While thinning of the cortices or trabeculae weakens bone, age-related changes in matrix composition also lower fracture resistance. This review summarizes how the organic matrix, mineral phase, and water compartments influence the mechanical behavior of bone, thereby identifying characteristics important to fracture risk.

Recent Findings: In the synthesis of the organic matrix, tropocollagen experiences various post-translational modifications that facilitate a highly organized fibril of collagen I with a preferred orientation giving bone extensibility and several toughening mechanisms. Being a ceramic, mineral is brittle but increases the strength of bone as its content within the organic matrix increases. With time, hydroxyapatite-like crystals experience carbonate substitutions, the consequence of which remains to be understood. Water participates in hydrogen bonding with organic matrix and in electrostatic attractions with mineral phase, thereby providing stability to collagen-mineral interface and ductility to bone.

Summary: Clinical tools sensitive to age- and disease-related changes in matrix composition that the affect mechanical behavior of bone could potentially improve fracture risk assessment.

Keywords: Mineral; Type 1 collagen; Bone quality; Advanced glycation end-product; Post-translation modifications; Water
Links

DOI: 10.1007/s11914-018-0433-0

PubMed: 29611037

WoS: 000431895600001
History

Online: 2018-04-03

Cited Works (41)

Year	Entry
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.
2013	Willett TL, Sutty S, Gaspar A, Avery N, Grynpas M. In vitro non-enzymatic ribation reduces post-yield strain accommodation in cortical bone. Bone. February 2013;52(2):611-622.
2015	Stock SR. The mineral–collagen interface in bone. Calcif Tiss Int. September 2015;97(3):262-280.
2015	Zimmermann EA, Busse B, Ritchie RO. The fracture mechanics of human bone: influence of disease and treatment. BoneKEy Rep. September 2015;4:743.
2017	Nilsson AG, Sundh D, Johansson L, Nilsson M, Mellström D, Rudäng R, Zoulakis M, Wallander M, Darelid A, Lorentzon M. Type 2 diabetes mellitus is associated with better bone microarchitecture but lower bone material strength and poorer physical function in elderly women: a population‐based study. J Bone Miner Res. May 2017;32(5):1062-1071.
2015	Granke M, Makowski AJ, Uppuganti S, Does MD, Nyman JS. Identifying novel clinical surrogates to assess human bone fracture toughness. J Bone Miner Res. July 2015;30(7):1290-1300.
2016	Furst JR, Bandeira LC, Fan W-W, Agarwal S, Nishiyama KK, McMahon DJ, Dworakowski E, Jiang H, Silverberg SJ, Rubin MR. Advanced glycation endproducts and bone material strength in type 2 diabetes. J Clin Endocrinol Metab. June 2016;101(6):2502-2510.
2015	Granke M, Does MD, Nyman JS. The role of water compartments in the material properties of cortical bone. Calcif Tiss Int. September 2015;97(3):292-307.
2013	Karim L, Tang SY, Sroga GE, Vashishth D. Differences in non-enzymatic glycation and collagen cross-links between human cortical and cancellous bone. Osteoporos Int. September 2013;24(9):2441-2447.
2010	Farlay D, Panczer G, Rey C, Delmas PD, Boivin G. Mineral maturity and crystallinity index are distinct characteristics of bone mineral. J Bone Min Metab. July 2010;28(4):433-445.
2014	Gallant MA, Brown DM, Hammond M, Wallace JM, Du J, Deymier-Black AC, Almer JD, Stock SR, Allen MR, Burr DB. Bone cell-independent benefits of raloxifene on the skeleton: a novel mechanism for improving bone material properties. Bone. April 2014;61:191-200.
2011	Donnelly E. Methods for assessing bone quality: a review. Clin Orthop Relat Res. August 2011;469:2128-2138.
2016	Diez-Perez A, Bouxsein M, Eriksen E, Khosla S, Nyman J, Papapoulos S, Tang S. Technical note: recommendations for a standard procedure to assess cortical bone at the tissue-level in vivo using impact microindentation. Bone Rep. December 2016;5:181-185.
2017	Lloyd AA, Gludovatz B, Riedel C, Luengo EA, Saiyed R, Marty E, Lorich DG, Lane JM, Ritchie RO, Busse B, Donnelly E. Atypical fracture with long-term bisphosphonate therapy is associated with altered cortical composition and reduced fracture resistance. Proc Natl Acad Sci USA. August 15, 2017;114(33):8722-8727.
1969	Currey JD. The mechanical consequences of variation in the mineral content of bone. J Biomech. March 1969;2(1):1-11.
2016	Granke M, Makowski AJ, Uppuganti S, Nyman JS. Prevalent role of porosity and osteonal area over mineralization heterogeneity in the fracture toughness of human cortical bone. J Biomech. September 6, 2016;49(13):2748-2755.
2006	Peterlik H, Roschger P, Klaushofer K, Fratzl P. From brittle to ductile fracture of bone. Nat Mater. January 2006;5(1):52-55.
2014	Farr JN, Drake MT, Amin S, Melton LJ III, McCready LK, Khosla S. In vivo assessment of bone quality in postmenopausal women with type 2 diabetes. J Bone Miner Res. April 2014;29(4):787-795.
2012	Bala Y, Depalle B, Farlay D, Douillard T, Meille S, Follet H, Chapurlat R, Chevalier J, Boivin G. Bone micromechanical properties are compromised during long-term alendronate therapy independently of mineralization. J Bone Miner Res. April 2012;27(4):825-834.
2015	Poundarik AA, Wu P-C, Evis Z, Sroga GE, Ural A, Rubin M, Vashishth D. A direct role of collagen glycation in bone fracture. J Mech Behav Biomed Mater. December 2015;52:120-130.
2004	Siris ES, Chen Y-T, Abbott TA, Barrett-Connor E, Miller PD, Wehren LE, Berger ML. Bone mineral density thresholds for pharmacological intervention to prevent fractures. Arch Intern Med. May 24, 2004;164(10):1108-1112.
2016	McCloskey EV, Odén A, Harvey NC, Leslie WD, Hans D, Johansson H, Barkmann R, Boutroy S, Brown J, Chapurlat R, Elders PJM, Fujita Y, Glüer C-C, Goltzman D, Iki M, Karlsson M, Kindmark A, Kotowicz M, Kurumatani N, Kwok T, Lamy O, Leung J, Lippuner K, Ljunggren Ö, Lorentzon M, Mellström D, Merlijn T, Oei L, Ohlsson C, Pasco JA, Rivadeneira F, Rosengren B, Sornay-Rendu E, Szulc P, Tamaki J, Kanis JA. A meta-analysis of trabecular bone score in fracture risk prediction and its relationship to FRAX. J Bone Miner Res. May 2016;31(5):940-948.
2000	Niebur GL, Feldstein MJ, Yuen JC, Chen TJ, Keaveny TM. High-resolution finite element models with tissue strength asymmetry accurately predict failure of trabecular bone. J Biomech. December 2000;33(12):1575-1583.
2003	Boskey A. Bone mineral crystal size. Osteoporos Int. September 2003;14(suppl 5):S16-S20.
2013	Gourion-Arsiquaud S, Lukashova L, Power J, Loveridge N, Reeve J, Boskey AL. Fourier transform infrared imaging of femoral neck bone: reduced heterogeneity of mineral-to-matrix and carbonate-to-phosphate and more variable crystallinity in treatment-naive fracture cases compared with fracture-free controls. J Bone Miner Res. January 2013;28(1):150-161.
2016	Demirtas A, Curran E, Ural A. Assessment of the effect of reduced compositional heterogeneity on fracture resistance of human cortical bone using finite element modeling. Bone. October 2016;91:92-101.
2008	Hansen U, Zioupos P, Simpson R, Currey JD, Hynd D. The effect of strain rate on the mechanical properties of human cortical bone. J Biomech Eng. February 2008;130(1):011011.
2012	Poundarik AA, Diab T, Sroga GE, Ural A, Boskey AL, Gundberg CM, Vashishth D. Dilatational band formation in bone. Proc Natl Acad Sci USA. November 20, 2012;109(47):19178-19183.
2008	Yerramshetty JS, Akkus O. The associations between mineral crystallinity and the mechanical properties of human cortical bone. Bone. March 2008;42(3):476-482.
2014	Carriero A, Zimmermann EA, Paluszny A, Tang SY, Bale H, Busse B, Alliston T, Kazakia G, Ritchie RO, Shefelbine SJ. How tough is brittle bone? investigating osteogenesis imperfecta in mouse bone. J Bone Miner Res. June 2014;29(6):1392-1401.
2008	Koester KJ, Ager JW III, Ritchie RO. The true toughness of human cortical bone measured with realistically short cracks. Nat Mater. August 2008;7(8):672-677.
2016	Torres AM, Matheny JB, Keaveny TM, Taylor D, Rimnac CM, Hernandez CJ. Material heterogeneity in cancellous bone promotes deformation recovery after mechanical failure. Proc Natl Acad Sci USA. March 15, 2016;113(11):2892-2897.
2004	Akkus O, Adar F, Schaffler MB. Age-related changes in physicochemical properties of mineral crystals are related to impaired mechanical function of cortical bone. Bone. March 2004;34(4):443-453.
2011	Gautieri A, Vesentini S, Redaelli A, Buehler MJ. Hierarchical structure and nanomechanics of collagen microfibrils from the atomistic scale up. Nano Lett. February 9, 2011;11(2):757-766.
2015	McNerny EMB, Gong B, Morris MD, Kohn DH. Bone fracture toughness and strength correlate with collagen cross-link maturity in a dose-controlled lathyrism mouse model. J Bone Miner Res. March 2015;30(3):455-464.
2005	Fantner GE, Hassenkam T, Kindt JH, Weaver JC, Birkedal H, Pechenik L, Cutroni JA, Cidade GAG, Stucky GD, Morse DE, Hansma PK. Sacrificial bonds and hidden length dissipate energy as mineralized fibrils separate during bone fracture. Nat Mater. August 2005;4(8):612-616.
2017	Paschalis EP, Gamsjaeger S, Klaushofer K. Vibrational spectroscopic techniques to assess bone quality. Osteoporos Int. August 2017;28(8):2275-2291.
2007	Almer JD, Stock SR. Micromechanical response of mineral and collagen phases in bone. J Struct Biol. February 2007;157(2):365-370.
2013	Nair AK, Gautieri A, Chang S-W, Buehler MJ. Molecular mechanics of mineralized collagen fibrils in bone. Nat Commun. 2013;r:1724.
2015	Unal M, Akkus O. Raman spectral classification of mineral- and collagen-bound water's associations to elastic and post-yield mechanical properties of cortical bone. Bone. December 2015;81:315-326.
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.

Cited By (24)

Year	Entry
2021	Peña Fernández M, Kao AP, Bonithon R, Howells D, link="bodey-andrew-j"Bodey AJ, Wanelik K, Witte F, Johnston R, Arora H, Tozzi G. Time-resolved in situ synchrotron-microct: 4D deformation of bone and bone analogues using digital volume correlation. Acta Biomater. September 1, 2021;131:424.
2020	Creecy A, Uppuganti S, Girard MR, Schlunk SG, Amah C, Granke M, Unal M, Does MD, Nyman JS. The age-related decrease in material properties of BALB/c mouse long bones involves alterations to the extracellular matrix. Bone. January 2020;130:115126.
2020	Zioupos P, Kirchner HOK, Peterlik H. Ageing bone fractures: the case of a ductile to brittle transition that shifts with age. Bone. February 2020;131:115176.
2021	Creecy A, Brown KL, Rose KL, Voziyan P, Nyman JS. Post-translational modifications in collagen type I of bone in a mouse model of aging. Bone. February 2021;143:115763.
2021	Mandair GS, Akhter MP, Esmonde-White FW, Lappe JM, Bare SP, Lloyd WR, Long JP, Lopez J, Kozloff KM, Recker RR, Morris MD. Altered collagen chemical compositional structure in osteopenic women with past fractures: a case-control Raman spectroscopic study. Bone. July 2021;148:115962.
2022	Willett TL, Voziyan P, Nyman JS. Causative or associative: a critical review of the role of advanced glycation end-products in bone fragility. Bone. October 2022;163:116485.
2023	Pendyala M, Stephen SJ, Vashishth D, Blaber EA, Chan DD. Loss of hyaluronan synthases impacts bone morphology, quality, and mechanical properties. Bone. July 2023;172:116779.
2023	Kochetkova T, Hanke MS, Indermaur M, Groetsch A, Remund S, Neuenschwander B, Michler J, Siebenrock KA, Zysset P, Schwiedrzik J. Composition and micromechanical properties of the femoral neck compact bone in relation to patient age, sex and hip fracture occurrence. Bone. December 2023;177:116920.
2019	Gustafsson A, Wallin M, Isaksson H. Age-related properties at the microscale affect crack propagation in cortical bone. J Biomech. October 11, 2019;95:109326.
2021	Unal M. Raman spectroscopic determination of bone matrix quantity and quality augments prediction of human cortical bone mechanical properties. J Biomech. April 15, 2021;119:110342.
2021	Karali A, Kao AP, Zekonyte J, Blunn G, Tozzi G. Micromechanical evaluation of cortical bone using in situ XCT indentation and digital volume correlation. J Mech Behav Biomed Mater. March 2021;115:104298.
2020	Aguirre TG, Ingrole A, Fuller L, Seek TW, Fiorillo AR, Sertich JJW, Donahue SW. Differing trabecular bone architecture in dinosaurs and mammals contribute to stiffness and limits on bone strain. PLoS One. August 19, 2020;15(8):e0237042.
2020	Sridevan SM. Genetic Determinants of Bone Growth [Master's thesis]. Boston University; 2020.
2020	Aguirre TG. Bio-Inspired Design for Engineering Applications: Empirical and Finite Element Studies of Biomechanically Adapted Porous Bone Architectures [PhD thesis]. Colorado State University; Summer 2020.
2022	Peruzzi CRP. Nanoscale Deformation Mechanisms and Yield Prediction of Lamellar Bone [PhD thesis]. Swiss Federal Institute of Technology Zürich; 2022.
2019	Gustafsson A. The Role of Microstructure for Crack Propagation in Cortical Bone [PhD thesis]. Lund, Sweden: Lund University; December 2019.
2022	Gupta SD. Mineralized Tissues At the Osteochondral Junction in Healthy and Osteoarthritic Joints: Advanced Microimaging and Mechanical Studies [PhD thesis]. University of Oulu; 2022.
2018	Peña Fernández M. X-Ray Biomechanical Imaging and Digital Volume Correlation of Bone: From Regeneration to Structure [PhD thesis]. Portsmouth, England: University of Portsmouth; December 2018.
2020	Karali A. Multi-Scale Evaluation of Bone Combining Indentation, in Situ XCT Mechanics and Digital Volume Correlation [PhD thesis]. Portsmouth, England: University of Portsmouth; 2020.
2022	Pendyala M. The Interplay Between Mechanics and Joint Health: A Focus on Hyaluronan and Inflammation [PhD thesis]. Troy, NY: Rensselaer Polytechnic Institute; December 2022.
2022	Tice MJL. Loss and Modulation of Bone Matrix and Fragility During Diabetes Mellitus [PhD thesis]. Troy, NY: Rensselaer Polytechnic Institute; May 2022.
2022	Blank MA. Defining Mechanisms by Which EphrinB2 in Osteocytes Controls Bone Strength and Material Quality [PhD thesis]. University of Melbourne; September 2022.
2018	Creecy A. Age- and Diabetes-Related Changes in the Matrix and Fracture Resistance of Bone [PhD thesis]. Nashville, TN: Vanderbilt University; August 10, 2018.
2020	Mancuso ME. Defining the Multiscale Relationship Between Subject-Specific Bone Strain and Structural Adaptation in the Distal Radius of Women [PhD thesis]. Worcester, MA: Worcester Polytechnic Institute; July 2020.