Bone composition:​ relationship to bone fragility and antiosteoporotic drug effects

Boskey, Adele L<sup>1,2</sup>

Affiliations

¹Musculoskeletal Integrity Program, Hospital for Special Surgery, affiliated with Weill Medical College of Cornell University, New York, NY, USA

²Department of Biophysics and Systems Biology, Weill Medical College of Cornell University, New York, NY, USA

Abstract and keywords

The composition of a bone can be described in terms of the mineral phase, hydroxyapatite, the organic phase, which consists of collagen type I, noncollagenous proteins, other components and water. The relative proportions of these various components vary with age, site, gender, disease and treatment. Any drug therapy could change the composition of a bone. This review, however, will only address those pharmaceuticals used to treat or prevent diseases of bone: fragility fractures in particular, and the way they can alter the composition. As bone is a heterogeneous tissue, its composition must be discussed in terms of the chemical makeup, properties of its chemical constituents and their distributions in the ever-changing bone matrix. Emphasis, in this review, is placed on changes in composition as a function of age and various diseases of bone, particularly osteoporosis. It is suggested that while some of the antiosteoporotic drugs can and do modify composition, their positive effects on bone strength may be balanced by negative ones.

Keywords:

Links

DOI: 10.1038/bonekey.2013.181. eCollection 2013

PubMed: 24501681

PubMedCentral: PMC3909232

WoS: 000375691500002

History

Received: 2013-07-09

Accepted: 2013-09-27

Online: 2013-12-04

Cited Works (33)

Year	Entry
2003	Paschalis EP, Boskey AL, Kassem M, Eriksen EF. Effect of hormone replacement therapy on bone quality in early postmenopausal women. J Bone Miner Res. June 2003;18(6):955-959.
2002	Currey JD. Bones: Structure and Mechanics. Princeton, NJ: Princeton University Press; 2002.
2010	Burghardt AJ, Kazakia GJ, Sode M, de Papp AE, Link TM, Majumdar S. A longitudinal HR-pQCT study of alendronate treatment in postmenopausal women with low bone density: relations among density, cortical and trabecular microarchitecture, biomechanics, and bone turnover. J Bone Miner Res. December 2010;25(12):2558-2571.
2010	Gourion-Arsiquaud S, Allen MR, Burr DB, Vashishth D, Tang SY, Boskey AL. Bisphosphonate treatment modifies canine bone mineral and matrix properties and their heterogeneity. Bone. March 2010;46(3):666-672.
2010	Boskey AL, Coleman R. Aging and bone. J Dent Res. December 2010;89(2):1333-1348.
2011	Gamsjaeger S, Buchinger B, Zwettler E, Recker R, Black D, Gasser JA, Eriksen EF, Klaushofer K, Paschalis EP. Bone material properties in actively bone-forming trabeculae in postmenopausal women with osteoporosis after three years of treatment with once-yearly zoledronic acid. J Bone Miner Res. January 2011;26(1):12-18.
2006	McCreadie BR, Morris MD, Chen T-c, Rao DS, Finney WF, Widjaja E, Goldstein SA. Bone tissue compositional differences in women with and without osteoporotic fracture. Bone. December 2006;39(6):1190-1195.
2008	Allen MR, Gineyts E, Leeming DJ, Burr DB, Delmas PD. Bisphosphonates alter trabecular bone collagen cross-linking and isomerization in beagle dog vertebra. Osteoporos Int. March 2008;19(3):329-337.
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.
2001	Roschger P, Rinnerthaler S, Yates J, Rodan GA, Fratzl P, Klaushofer K. Alendronate increases degree and uniformity of mineralization in cancellous bone and decreases the porosity in cortical bone of osteoporotic women. Bone. August 2001;29(2):185-191.
2012	Donnelly E, Meredith DS, Nguyen JT, Gladnick BP, Rebolledo BJ, Shaffer AD, Lorich DG, Lane JM, Boskey AL. Reduced cortical bone compositional heterogeneity with bisphosphonate treatment in postmenopausal women with intertrochanteric and subtrochanteric fractures. J Bone Miner Res. March 2012;27(3):672-678.
2008	Roschger P, Paschalis EP, Fratzl P, Klaushofer K. Bone mineralization density distribution in health and disease. Bone. March 2008;42(3):456-466.
2012	Estrada K, Styrkarsdottir U, Evangelou E, Hsu Y-H, Duncan EL, Ntzani EE, Oei L, Albagha OME, Amin N, Kemp JP, Koller DL, Li G, Liu C-T, Minster RL, Moayyeri A, Vandenput L, Willner D, Xiao S-M, Yerges-Armstrong LM, Zheng H-F, Alonso N, Eriksson J, Kammerer CM, Kaptoge SK, Leo PJ, Thorleifsson G, Wilson SG, Wilson JF, Aalto V, Alen M, Aragaki AK, Aspelund T, Center JR, Dailiana Z, Duggan DJ, Garcia M, Garcia-Giralt N, Giroux S, Hallmans G, Hocking LJ, Husted LB, Jameson KA, Khusainova R, Kim GS, Kooperberg C, Koromila T, Kruk M, Laaksonen M, Lacroix AZ, Lee SH, Leung PC, Lewis JR, Masi L, Mencej-Bedrac S, Nguyen TV, Nogues X, Patel MS, Prezelj J, Rose LM, Scollen S, Siggeirsdottir K, Smith AV, Svensson O, Trompet S, Trummer O, van Schoor NM, Woo J, Zhu K, Balcells S, Brandi ML, Buckley BM, Cheng S, Christiansen C, Cooper C, Dedoussis G, Ford I, Frost M, Goltzman D, González-Macías J, Kähönen M, Karlsson M, Khusnutdinova E, Koh J-M, Kollia P, Langdahl BL, Leslie WD, Lips P, Ljunggren Ö, Lorenc RS, Marc J, Mellström D, Obermayer-Pietsch B, Olmos JM, Pettersson-Kymmer U, Reid DM, Riancho JA, Ridker PM, Rousseau F, Slagboom PE, Tang NLS, Urreizti R, Van Hul W, Viikari J, Zarrabeitia MT, Aulchenko YS, Castano-Betancourt M, Grundberg E, Herrera L, Ingvarsson T, Johannsdottir H, Kwan T, Li R, Luben R, Medina-Gómez C, Palsson ST, Reppe S, Rotter JI, Sigurdsson G, van Meurs JBJ, Verlaan D, Williams FMK, Wood AR, Zhou Y, Gautvik KM, Pastinen T, Raychaudhuri S, Cauley JA, Chasman DI, Clark GR, Cummings SR, Danoy P, Dennison EM, Eastell R, Eisman JA, Gudnason V, Hofman A, Jackson RD, Jones G, Jukema JW, Khaw K-T, Lehtimäki T, Liu Y, Lorentzon M, McCloskey E, Mitchell BD, Nandakumar K, Nicholson GC, Oostra BA, Peacock M, Pols HAP, Prince RL, Raitakari O, Reid IR, Robbins J, Sambrook PN, Sham PC, Shuldiner AR, Tylavsky FA, van Duijn CM, Wareham NJ, Cupples LA, Econs MJ, Evans DM, Harris TB, Kung AWC, Psaty BM, Reeve J, Spector TD, Streeten EA, Zillikens MC, Thorsteinsdottir U, Ohlsson C, Karasik D, Richards JB, Brown MA, Stefansson K, Uitterlinden AG, Ralston SH, Ioannidis JPA, Kiel DP, Rivadeneira F. Genome-wide meta-analysis identifies 56 bone mineral density loci and reveals 14 loci associated with risk of fracture. Nat Genet. April 15, 2012;44(5):491-501.
2008	Techawiboonwong A, Song HK, Leonard MB, Wehrli FW. Cortical bone water: in vivo quantification with ultrashort echo-time MR imaging. Radiology. September 2008;248(3):824-833.
2005	Boskey AL, Mendelsohn R. Infrared analysis of bone in health and disease. J Biomed Opt. May–June 2005;10(3):031102.
2011	Paschalis EP, Tatakis DN, Robins S, Fratzl P, Manjubala I, Zoehrer R, Gamsjaeger S, Buchinger B, Roschger A, Phipps R, Boskey AL, Dall'Ara E, Varga P, Zysset P, Klaushofer K, Roschger P. Lathyrism-induced alterations in collagen cross-links influence the mechanical properties of bone material without affecting the mineral. Bone. December 2011;49(6):1232-1241.
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.
2001	Dempster DW, Cosman F, Kurland ES, Zhou H, Nieves J, Woelfert L, Shane E, Plavetić K, Müller R, Bilezikian J, Lindsay R. Effects of daily treatment with parathyroid hormone on bone microarchitecture and turnover in patients with osteoporosis: a paired biopsy study. J Bone Miner Res. October 2001;16(10):1846-1853.
2005	Odetti P, Rossi S, Monacelli F, Poggi A, Cirnigliaro M, Federici M, Federici A. Advanced glycation end products and bone loss during aging. Annals NY Acad Sci. 2005;1043:710-717.
2000	Carden A, Morris MD. Application of vibrational spectroscopy to the study of mineralized tissues (review). J Biomed Opt. July 2000;5(3):259-268.
2008	Recker RR, Delmas PD, Halse J, Reid IR, Boonen S, García-Hernandez PA, Supronik J, Lewiecki EM, Ochoa L, Miller P, Hu H, Mesenbrink P, Hartl F, Gasser J, Eriksen EF. Effects of intravenous zoledronic acid once yearly on bone remodeling and bone structure. J Bone Miner Res. January 2008;23(1):6-16.
2009	Gourion‐Arsiquaud S, Burket JC, Havill LM, DiCarlo E, Doty SB, Mendelsohn R, van der Meulen MCH, Boskey AL. Spatial variation in osteonal bone properties relative to tissue and animal age. J Bone Miner Res. July 2009;24(7):1271-1281.
2008	Ruppel ME, Miller LM, Burr DB. The effect of the microscopic and nanoscale structure on bone fragility. Osteoporos Int. September 2008;19(9):1251-1265.
2006	Zoehrer R, Roschger P, Paschalis EP, Hofstaetter JG, Durchschlag E, Fratzl P, Phipps R, Klaushofer K. Effects of 3- and 5-year treatment with risedronate on bone mineralization density distribution in triple biopsies of the iliac crest in postmenopausal women. J Bone Miner Res. July 2006;21(7):1106-1112.
2013	Spatz JM, Ellman R, Cloutier AM, Louis L, van Vliet M, Suva LJ, Dwyer D, Stolina M, Ke HZ, Bouxsein ML. Sclerostin antibody inhibits skeletal deterioration due to reduced mechanical loading. J Bone Miner Res. April 2013;28(4):865-874.
2009	Gourion‐Arsiquaud S, Faibish D, Myers E, Spevak L, Compston J, Hodsman A, Shane E, Recker RR, Boskey ER, Boskey AL. Use of FTIR spectroscopic imaging to identify parameters associated with fragility fracture. J Bone Miner Res. September 2009;24(9):1565-1571.
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.
2003	Young MF. Bone matrix proteins: their function, regulation, and relationship to osteoporosis. Osteoporos Int. March 2003;14(suppl 3):S35-S42.
2012	Sroga GE, Vashishth D. Effects of bone matrix proteins on fracture and fragility in osteoporosis. Curr Osteoporos Rep. June 2012;10(2):141-150.
2011	Morris MD, Mandair GS. Raman assessment of bone quality. Clin Orthop Relat Res. August 2011;469:2160-2169.
2004	Paschalis EP, Shane E, Lyritis G, Skarantavos G, Mendelsohn R, Boskey AL. Bone fragility and collagen cross‐links. J Bone Miner Res. December 2004;19(12):2000-2004.
2007	Vashishth D. The role of the collagen matrix in skeletal fragility. Curr Osteoporos Rep. June 2007;5(2):62-66.
2006	Durchschlag E, Paschalis EP, Zoehrer R, Roschger P, Fratzl P, Recker R, Phipps R, Klaushofer K. Bone material properties in trabecular bone from human iliac crest biopsies after 3‐ and 5‐year treatment with risedronate. J Bone Miner Res. October 2006;21(10):1581-1590.

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2020	Maghsoudi-Ganjeh M, Wang X, Zeng X. Nanomechanics and ultrastructure of bone: a review. Comput Model Eng Sci. 2020;125(1):1-32.
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.
2018	Frank M, Marx D, Nedelkovski V, Fischer J-T, Pahr DH, Thurner PJ. Dehydration of individual bovine trabeculae causes transition from ductile to quasi-brittle failure mode. J Mech Behav Biomed Mater. November 2018;87:296-305.
2020	Huo SH, Jiang C, Cui X, Liu GR. A high-fidelity 3D S-FEM stress analysis of a highly heterogeneous swine skull. Med Biol Eng Comput. March 2020;58(3):625-641.
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	Billington E. Emerging Issues in Osteoporosis [MD thesis]. Auckland, New Zealand: University of Auckland; 2017.
2017	Unal M. Classification of Bound Water and Collagen Denaturation Status of Cortical Bone by Raman Spectroscopy [PhD thesis]. Cleveland, OH: Case Western Reserve University; January 2017.
2015	Cabahug-Zuckerman P. A Β₃ Integrin Based Mechanosome in Bone Tissue Osteocytes: Plasticity to Changes in Mechanical Loading [PhD thesis]. New York, NY: The City College of New York; 2015.
2017	Cresswell EN. Spatial Regulation of Bone Formation in Functional Adaptation of Cancellous Bone [PhD thesis]. Ithaca, NY: Cornell University; May 2017.
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.
2018	Hunt HB. Characterization of Material Properties, Microarchitecture, and Mechanics of Bone from Subjects With Type 2 Diabetes Mellitus [PhD thesis]. Ithaca, NY: Cornell University; December 2018.
2018	Torres AM. Fatigue Behavior of Cancellous Bone, Microdamage Accumulation, and Biologically Inspired Cellular Solids [PhD thesis]. Ithaca, NY: Cornell University; August 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.
2018	Huynh NPT. Bioinformatics and Molecular Approaches for the Development of Biological Artificial Cartilage [PhD thesis]. Duke University; 2018.
2018	Raina DB. Biomaterials as Carriers for Bone Active Molecules: An Approach to Create Off-the-Shelf Bone Substitutes [PhD thesis]. Lund, Sweden: Lund University; 2018.
2019	Nobakhti S. Multiscale Characteristics of Bone Toughness [PhD thesis]. Northeastern University; July 2019.
2020	O’Sullivan LM. Time-Sequence of Biomechanical Adaption in Trabecular Tissue During Estrogen Deficiency [PhD thesis]. National University of Ireland Galway; March 2020.
2019	Beltejar M-JG. Understanding the Genetic Basis for Bone-Matrix Quality [PhD thesis]. University of Rochester; 2019.
2019	Maynard RD. Establishing the Functional Role of Cped1* in the Genetic Regulation of the Osteoblast* [PhD thesis]. University of Rochester; 2019.
2016	Bailey SM. The Role of Extra-Cellular Matrix Proteins and Post-Translational Modifications on Bone Fracture [PhD thesis]. Troy, NY: Rensselaer Polytechnic Institute; September 2016.
2020	Marinho L. The Relationship Between Fracture Morphology and Bone Biomechanics: A Study of Changes Occurring in Juvenile Porcine Ribs Over the Early Postmortem Interval [PhD thesis]. Simon Fraser University; 2020.
2016	Wittkowske C. The Role of Mechanical Forces in Bone Formation: Evaluation of Long-Term Responses by Osteoblasts to Low Fluid Shear Stress in Vitro [PhD thesis]. University of Sheffield; September 2016.
2017	Gonzalez Fernandez T. Integrating Non-Viral Gene Therapy and 3D Bioprinting for Bone, Cartilage and Osteochondral Tissue Engineering [PhD thesis]. Trinity College Dublin; December 2017.
2021	Frank M. Mechanical Characterization of Individual Trabeculae [PhD thesis]. Vienna University of Technology; February 2021.
2019	Colón-Bernal ID. Unraveling Chemical Composition Heterogeneity of Type I Collagen in Trabecular Bone as a Function of Disease and Treatment [PhD thesis]. University of Michigan; 2019.
2020	Sun Y. Investigation of Actions of Parathyroid Hormone-Related Protein (PTHrP) Independent of PTH1R [PhD thesis]. University of Melbourne; June 2020.
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.
2016	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; 2016.
2021	Harrison KD. A Novel in Vivo Synchrotron Radiation Micro-CT Imaging Platform for the Direct Tracking of Remodeling Events in Cortical Bone [PhD thesis]. University of Saskatchewan; December 2021.
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.
2018	Zhang L. Effects of Osteoblast-Specific Gα_S Overexpression on Skeletal Development and Response to Catabolic and Anabolic Stimuli Using a Transgenic Mouse Model [PhD thesis]. University of Toronto; 2018.
2020	Maghsoudi-Ganjeh M. Computational Investigation of Ultrastructural Behavior of Bone and Bone-Inspired Materials [PhD thesis]. San Antionio, TX: University of Texas at San Antonio; May 2020.
2019	Demirtas A. Assessment of the Influence of Possible Side Effects of Long-Term Bisphosphonate Treatment on Cortical Bone Fracture Resistance Using Finite Element Modeling [PhD thesis]. Villanova, PA: Villanova University; July 2019.
2018	Buettmann E. The Role of Bisphosphonates and Osteoblast Lineage Cells in Promoting Osteogenic and Angiogenic Processes Necessary for Bone Repair [PhD thesis]. St. Louis, MO: Washington University in St. Louis; December 2018.
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