Skip to main content
SpringerLink
Log in

The Role of Collagen Organization on the Properties of Bone

  • Original Research
  • Published:
Calcified Tissue International Aims and scope Submit manuscript

An Erratum to this article was published on 13 May 2015

Abstract

Bone is a complex tissue constituted by a collagen matrix filled in with crystal of hydroxyapatite (HAP). Bone mechanical properties are influenced by the collagen matrix which is organized into hierarchical structures from the individual type I collagen heterotrimer flanked by linear telopeptides at each end to the collagen fibrils that are interconnected by enzymatic and non-enzymatic cross-links. Although most studies focused on the role of collagen cross-links in bone strength, other organizational features may also play a role. At the molecular level it has been shown that homotrimer of type I collagen found in bone tissue of some patients with osteogenesis imperfecta (OI) is characterized by decreased mechanical competence compared to the regular heterotrimer. The state of C-telopeptide isomerization—which can be estimated by the measurement in body fluids of the native and isomerized isoforms—has also been shown to be associated with bone strength, particularly the post-yield properties independent of bone size and bone mineral density. Other higher hierarchical features of collagen organization have shown to be associated with changes in bone mechanical behavior in ex vivo models and may also be relevant to explain bone fragility in diseases characterized by collagen abnormalities e.g., OI and Paget’s disease. These include the orientation of collagen fibrils in a regular longitudinal direction, the D-spacing period between collagen fibrils and the collagen-HAP interfacial bonding. Preliminary data indicate that some of these organizational features can change during treatment with bisphosphonate, raloxifene, and PTH suggesting that they may contribute to their anti-fracture efficacy. It remains however to be determined which of these parameters play a specific and independent role in bone matrix properties, what is the magnitude of mechanical strength explained by collagen organization, whether they are relevant to explain osteoporosis-induced bone fragility, and how they could be monitored non-invasively to develop efficient bone quality biomarkers.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Schuit SC, van der Klift M, Weel AE, de Laet CE, Burger H, Seeman E, Hofman A, Uitterlinden AG, van Leewen JP, Pols HA (2004) Fracture incidence and association with bone mineral density in elderly men and women: the Rotterdam Study. Bone 34:195–202

    Article  CAS  PubMed  Google Scholar 

  2. Sornay-Rendu E, Munoz F, Garnero P, Duboeuf F, Delmas PD (2005) Identification of osteopenic women at high risk of fracture: the OFELY Study. J Bone Miner Res 20:1813–1819

    Article  PubMed  Google Scholar 

  3. Nyman JS, Reyes M, Wang X (2005) Effect of ultrastructural changes on the toughness of bone. Micron 35:566–582

    Article  Google Scholar 

  4. Nyman JS, Roy A, Tyler JH, Acuna RL, Gayle HJ, Wang X (2007) Age-related factors affecting the postyield energy dissipation of human cortical bone. J Orthop Res 25:646–655

    Article  PubMed Central  PubMed  Google Scholar 

  5. Wang X, Bank RA, Tekoppele JM, Agrawal CM (2001) The role of collagen in determining bone mechanical properties. J Orthop Res 19:1021–1026

    Article  CAS  PubMed  Google Scholar 

  6. Stefan U, Michael B, Werner S (2010) Effects of three different preservation methods on the mechanical properties of human and bovine cortical bone. Bone 47:1048–1053

    Article  CAS  PubMed  Google Scholar 

  7. Currey JD, Foreman J, Laketic I, Mitchell J, Pegg DE, Reilly GC (1997) Effects of ionizing radiation on the mechanical properties of human bone. J Orthop Res 15:111–117

    Article  CAS  PubMed  Google Scholar 

  8. Barth HD, Launey ME, Macdowell AA, Ager JW 3rd, Ritchie RO (2010) On the effect of X-ray irradiation on the deformation and fracture behavior of human cortical bone. Bone 46:1475–1485

    Article  PubMed  Google Scholar 

  9. Burton B, Gaspar A, Josey D, Tupy J, Grynpas MD, Willet T (2014) Bone embrittlement and collagen modifications due to high—dose gamma-irradiation sterilization. Bone 61:71–81

    Article  CAS  PubMed  Google Scholar 

  10. Stroga GE, Vashishth D (2012) Effects of bone matrix proteins on fracture and fragility in osteoporosis. Curr Osteoporos Rep 10:141–150

    Article  Google Scholar 

  11. Niyibizi C, Eyre DR (1989) Bone type V collagen: chain composition and location of a trypsin cleavage site. Connect Tissue Res 20:247–250

    Article  CAS  PubMed  Google Scholar 

  12. Nimni ME (1993) Fibrillar collagens: their biosynthesis, molecular structure, and mode of assembly. In: Zern MA, Reid LM (eds) Extracellular matrix: chemistry, biology, and pathobiology with emphasis on the liver. Marcel Dekker Inc., New York, pp 121–148

    Google Scholar 

  13. Berg RA, Prockop DJ (1973) The thermal transition of a non-hydroxylated form of collagen. Evidence for a role for hydroxyproline in stabilizing the triple-helix of collagen. Biochem Biophys Res Commun 52:115–120

    Article  CAS  PubMed  Google Scholar 

  14. Harwood R, Grant ME, Jackson DS (1975) Studies on the glycosylation of hydroxylysine residues during collagen biosynthesis and the subcellular localization of collagen galactosyltransferase and collagen glucosyltransferase in tendon and cartilage cells. Biochem J 152:291–302

    CAS  PubMed Central  PubMed  Google Scholar 

  15. Gineyts E, Garnero P, Delmas PD (2001) Urinary excretion of glucosyl-galactosyl pyridinoline: a specific biochemical marker of synovium degradation. Rheumatology (Oxford) 40:315–323

    Article  CAS  Google Scholar 

  16. Pinnell SR, Fox R, Krane SM (1971) Human collagens: differences in glycosylated hydroxylysines in skin and bone. Biochim Biophys Acta 229:119–122

    Article  CAS  PubMed  Google Scholar 

  17. Petruska JA, Hodge AJ (1964) A subunit model for the tropocollagen macromolecule. Proc Natl Acad Sci USA 51:871–876

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  18. Fledelius C, Johnsen AH, Cloos PA, Bode M, Qvist P (1997) Characterization of urinary degradation products derived from type I collagen. Identification of a beta-isomerized Asp-Gly sequence within the C-terminal telopeptides (alpha 1) region. J Biol Chem 272(15):9755–9763

    Article  CAS  PubMed  Google Scholar 

  19. Cloos PA, Fledelius C (2000) Collagen fragments in urine derived from bone resorption are highly racemized and isomerized: a biological clock of protein aging with clinical potential. Biochem J 345:473–480

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  20. Borel O, Gineyts E, Bertholon C, Garnero P (2012) Cathepsin K preferentially solubilizes matured bone matrix. Calcif Tissue Int 911:32–39

    Article  Google Scholar 

  21. Garnero P, Borel O, Gineyts E, Duboeuf F, Solberg H, Bouxsein ML, Christiansen C, Delmas PD (2006) Extracellular post-translational modifications of collagen are major determinants of biomechanical properties of fetal bovine cortical bone. Bone 38:300–309

    Article  CAS  PubMed  Google Scholar 

  22. Garnero P, Fledelius C, Gineyts E, Serre CM, Vignot E, Delmas PD (1997) Decreased beta-isomerization of the C-terminal telopeptide of type I collagen alpha 1 chain in Paget’s disease of bone. J Bone Miner Res 12:1407–1415

    Article  CAS  PubMed  Google Scholar 

  23. Leeming DJ, Delling G, Koizumi M, Henriksen K, Karsdal MA, Li B, Qvist P, Tanko LB, Byrjalsen I (2006) Alpha CTX as a biomarker of skeletal invasion of breast cancer: immunolocalization and the load dependency of urinary excretion. Cancer Epidemiol Biomarkers Prev 15:1392–1395

    Article  CAS  PubMed  Google Scholar 

  24. Kuznetsova N, McBride DJ Jr, Leikin S (2001) Osteogenesis imperfecta murine: interaction between type I collagen homotrimers. J Mol Biol 309:807–815

    Article  CAS  PubMed  Google Scholar 

  25. Jimenez SA, Bashey RI, Yankowski R (1977) Identification of collagen alpha1(I) trimer in embryonic chick tendons and calvaria. Biochem Biophys Res Commun 78:1354–1361

    Article  CAS  PubMed  Google Scholar 

  26. Rojkind M, Giambrone MA, Biempica L (1979) Collagen types in normal and cirrhotic liver. Gastroenterology 76:710–719

    CAS  PubMed  Google Scholar 

  27. Makareeva E, Han S, Leikin S (2010) Carcinomas contain a matrix metalloproteinase-resistant isoform of type I collagen exerting selective support to invasion. Cancer Res 70:4366–4374

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  28. Rupard JH, Dimar SJ, Haralson MA (1988) Synthesis of type I homotrimer collagen molecules by cultured human lung adenocarcinoma cells. Am J Pathol 133:316–326

    CAS  PubMed Central  PubMed  Google Scholar 

  29. Bailey AJ, Sims TJ, Knott L (2002) Phenotypic expression of osteoblast collagen in osteoarthritic bone: production of type I homotrimer. Int J Biochem Cell Biol 34:176–182

    Article  CAS  PubMed  Google Scholar 

  30. Mann V, Hobson EE, Li B, Stewart TL, Grant SF, Robins SP, Aspden RM, Ralston SH (2001) A COL1A1 Sp1 binding site polymorphism predisposes to osteoporotic fracture by affecting bone density and quality. J Clin Invest 107:899–907

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  31. Grant SF, Reid DM, Blake G, Herd R, Fogelman I, Ralston SH (1996) Reduced bone density and osteoporosis associated with a polymorphic Sp1 binding site in the collagen type I alpha 1 gene. Nat Genet 14:203–205

    Article  CAS  PubMed  Google Scholar 

  32. Mann V, Ralston SH (2003) Meta-analysis of COL1A1 Sp1 polymorphism in relation to bone mineral density and osteoporotic fracture. Bone 32:711–717

    Article  CAS  PubMed  Google Scholar 

  33. Ralston SH, Uitterlinden AG, Brandi ML, Balcells S, Langdahl BL, Lips P, Lorenc R, Obermayer-Pietsch B, Scollen S, Bustamante M, Husted LB, Carey AH, Diez-Perez A, Dunning AM, Falchetti A, Karczmarewicz E, Kruk M, van Leeuwen JP, van Meurs JB, Mangion J, McGuigan FE, Mellibovsky L, del Monte F, Pols HA, Reeve J, Reid DM, Renner W, Rivadeneira F, van Schoor NM, Sherlock RE, Ioannidis JP (2006) Large-scale evidence for the effect of the COLIA1 Sp1 polymorphism on osteoporosis outcomes: the GENOMOS study. PLoS Med 3:e90

    Article  PubMed Central  PubMed  Google Scholar 

  34. Saban J, Zussman M, King D (1996) Heterozygous oim mice exhibit a mild form of osteogenesis imperfecta. Bone 19:575–579

    Article  CAS  PubMed  Google Scholar 

  35. Misof K, Landis WJ, Fratzl P (1997) Collagen from the osteogenesis imperfecta mouse model (oim) shows reduced resistance against tensile stress. J Clin Invest 100:40–45

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  36. Camacho NP, Hou L, Boskey AL (1999) The material basis for reduced mechanical properties in oim mice bones. J Bone Miner Res 14:264–272

    Article  CAS  PubMed  Google Scholar 

  37. Miller E, Delos D, Pleshko Camacho N (2007) Abnormal mineral-matrix interactions are a significant contributor to fragility in oim/oim bone. Calcif Tissue Int 81:206–214

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  38. McBride DJ, Choe V, Brodsky B (1997) Altered collagen structure in mouse tail tendon lacking the alpha 2(I) chain. J Mol Biol 270:275–284

    Article  CAS  PubMed  Google Scholar 

  39. Miles CA, Sims TJ, Bailey AJ (2002) The role of the alpha2 chain in the stabilization of the collagen type I heterotrimer: a study of the type I homotrimer in oim mouse tissues. J Mol Biol 321:797–805

    Article  CAS  PubMed  Google Scholar 

  40. Nelson MT, Humphrey W, Schulten K (1996) NAMD: a parallel, object-oriented molecular dynamics program. Int J High Perform Comput Appl 10:251–268

    Article  Google Scholar 

  41. MacKerell AD, Bashford D, Karplus M (1998) All-atom empirical potential for molecular modeling and dynamics studies of proteins. J Phys Chem B 102:3586–3616

    Article  CAS  PubMed  Google Scholar 

  42. Chang S-W, Shefelbine SJ, Buehler MJ (2012) Structural and mechanical differences between collagen homo- and heterotrimers: relevance for the molecular origin of brittle bone disease. Biophys J 102:640–648

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  43. Viguet-Carrin S, Roux JP, Arlot ME, Merabet Z, Leeming DJ, Byrjalsen I, Delmas PD, Bouxtein M (2006) Contribution of the advanced glycation end product pentosidine and of maturation of type I collagen to compressive biomechanical properties of human lumbar vertebrae. Bone 39:1073–1079

    Article  CAS  PubMed  Google Scholar 

  44. Goldman HM, Bromage TG, Thomas CD, Clement JG (2003) Preferred collagen fiber orientation in the human mid-shaft femur. Anat Rec A 272:434–445

    Article  Google Scholar 

  45. Hert J, Fiala P, Petryl M (1994) Osteon orientation of the diaphysis of the long bones in man. Bone 15:269–277

    Article  CAS  PubMed  Google Scholar 

  46. Martin RB, Boardman DL (1993) The effects of collagen fiber orientation, porosity, density, and mineralization bovine cortical bone bending properties. J Biomech 26:1047–1054

    Article  CAS  PubMed  Google Scholar 

  47. Martin RB, Lau ST, Mathews PV, Gibson VA, Stovert SM (1996) Collagen fiber organization is related to mechanical properties and remodelling in equine bone. A comparison of two methods. J Biomechanics 29:1515–1521

    Google Scholar 

  48. Ramasamya JG, Akkusb O (2007) Local variations in the micromechanical properties of mouse femur: the involvement of collagen fiber orientation and mineralization. J Biomech 40:910–918

    Article  Google Scholar 

  49. Silva MJ, Brodt MB, Ettner SL (2002) Long bones from the senescence accelerated mouse SAMP6 have increased size but reduced whole-bone strength and resistance to fracture. J Bone Miner Res 17:1597–1603

    Article  PubMed  Google Scholar 

  50. Silva MJ, Brodt MD, Wopenka B, Thomopoulos S, Williams D, Wassen MHM, Ko M, Kusano N, Bank RA (2006) Decreased collagen organization and content are associated with reduced strength of demineralized and intact bone in the SAMP6 mouse. J Bone Miner Res 21:78–88

    Article  PubMed  Google Scholar 

  51. Puustjarvi K, Nieminen J, Rasanen T, Hyttinen M, Helminen HJ, Kroger H, Huuskonen J, Alhava E, Kovanen V (2003) Do more highly organized collagen fibrils increase bone mechanical strength in loss of mineral density after one-year running training? J Bone Miner Res 14:321–329

    Article  Google Scholar 

  52. Mikkonen L, Tuominen T, Kulonen E (1960) Collagen fractions in lathyritic rats. Biochem Pharmacol 3:181–183

    Article  CAS  PubMed  Google Scholar 

  53. Lees S, Barnard S, Mook H (1987) Neutron studies of collagenic lathyritic bone. Int J Biol Macromol 9:32–38

    Article  CAS  Google Scholar 

  54. Rauch F, Glorieux FH (2004) Osteogenesis imperfecta. Lancet 363:1377–1385

    Article  CAS  PubMed  Google Scholar 

  55. Rauch F, Travers R, Parfitt AM, Glorieux FH (2000) Static and dynamic bone histomorphometry in children with osteogenesis imperfecta. Bone 26:581–589

    Article  CAS  PubMed  Google Scholar 

  56. Eyre DR, Weis MA (2013) Bone collagen: new clues to its mineralization mechanism from recessive osteogenesis imperfecta. Calcif Tissue Int 93:338–347

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  57. Cassela JP, Yousuf Ali S (1992) Abnormal collagen and mineral formation in osteogenesis imperfecta. Bone Miner 17:123–128

    Article  Google Scholar 

  58. Cassela JP, Stamp TCB, Ali SY (1996) A morphological and ultrastructural study of bone in osteogenesis imperfecta. Calcif Tissue Int 58:155–165

    Article  Google Scholar 

  59. Sarathchandra P, Pope FM, Ali SY (1999) Morphometric analysis of type I collagen fibrils in the osteoid of osteogenesis imperfecta. Calcif Tissue Int 65:390–395

    Article  CAS  PubMed  Google Scholar 

  60. Kirsch E, Krieg T, Remberger K, Fendel H, Bruckner P, Muller PK (1981) Disorder of collagen metabolism in a patient with osteogenesis imperfecta (lethal type): increased degree of hydroxylation of lysine in collagen type I and III. Eur J Clin Invest 11:39–47

    Article  CAS  PubMed  Google Scholar 

  61. Garnero P, Schott AM, Prockop D, Chevrel G (2009) Bone turnover and type I collagen C-telopeptide isomerization in adult osteogenesis imperfecta: associations with collagen gene mutations. Bone 44:461–466

    Article  CAS  PubMed  Google Scholar 

  62. Chipman SD, Sweet HO, McBride DJ Jr, Davisson MT, Marks SC Jr, Shuldiner AR, Wenstrup RJ, Rowe DW, Shapiro JR (1993) Defective pro alpha 2(I) collagen synthesis in a recessive mutation in mice: a model of human osteogenesis imperfecta. Proc Natl Acad Sci USA 90:1701–1705

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  63. Bonadio J, Saunders TL, Tsai E, Goldstein SA, Morris-Wiman J, Brinkley L, Dolan DF, Altschuler RA, Hawkins JE Jr, Bateman JF (1990) Transgenic mouse model of the mild dominant form of osteogenesis imperfecta. Proc Natl Acad Sci USA 87:7145–7149

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  64. Forlino A, Porter FD, Lee EJ, Westphal H, Marini JC (1999) Use of the Cre/lox recombination system to develop a non-lethal knock-in murine model for osteogenesis imperfecta with an alpha1(I) G349C substitution. Variability in phenotype in Brtl IV mice. J Biol Chem 274:37923–37931

    Article  CAS  PubMed  Google Scholar 

  65. Morello R, Bertin TK, Chen Y, Hicks J, Tonachini L, Monticone M, Castagnola P, Rauch F, Glorieux FH, Vranka J, Bächinger HP, Pace JM, Schwarze U, Byers PH, Weis M, Fernandes RJ, Eyre DR, Yao Z, Boyce BF, Lee B (2006) CRTAP is required for prolyl 3-hydroxylation and mutations cause recessive osteogenesis imperfecta. Cell 127:291–304

    Article  CAS  PubMed  Google Scholar 

  66. Sims TJ, Miles CA, Bailey AJ, Camacho NP (2003) Properties of collagen in oim mouse tissues. Connect Tissue Res 44(Suppl 1):202–205

    Article  CAS  PubMed  Google Scholar 

  67. Miller E, Delos D, Baldini T, Wright TM, Camacho NP (2007) Abnormal mineral-matrix interactions are a significant contributor to fragility in oim/oim bone. Calcif Tissue Int 81:206–214

    Article  Google Scholar 

  68. Jepsen KJ, Goldstein SA, Kuhn JL, Schaffler MB, Bonadio J (1996) Type-I collagen mutation compromises the post-yield behavior of Mov13 long bone. J Orthop Res 14:493–499

    Article  CAS  PubMed  Google Scholar 

  69. Kuznetsovaa NV, Forlinob A, Cabralb WA, Marinib JC, Leikina S (2004) Structure, stability and interactions of type I collagen with GLY349-CYS substitution in α1(I) chain in a murine Osteogenesis Imperfecta model. Matrix Biol 23:101–112

    Article  Google Scholar 

  70. Wallace JM, Orr BG, Marini JC, Banaszak Holl MM (2011) Nanoscale morphology of type I collagen is altered in the Brtl mouse model of Osteogenesis Imperfecta. J Struct Biol 173:146–152

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  71. Gutsmann T, Fantner GE, Kindt JH, Venturoni M, Danielsen S, Hansma PK (2004) Force spectroscopy of collagen fibers to investigate their mechanical properties and structural organization. Biophys J 86:3186–3193

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  72. van der Rijt JAJ, van der Werf KO, Bennink ML, Dijkstra PJ, Feijen J (2006) Micromechanical testing of individual collagen fibrils. Macromol Biosci 6:697–702

    Article  PubMed  Google Scholar 

  73. Wallace JM, Erickson B, Les CM, Orr BG, Banaszak Holl MM (2010) Distribution of type I collagen morphologies in bone: relation to estrogen depletion. Bone 46:1349–1354

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  74. Meunier PJ, Coindre JM, Edouard CM, Arlot ME (1980) Bone histomorphometry in Paget’s disease. Quantitative and dynamic analysis of Pagetic and non-Pagetic bone tissue. Arthritis Rheum 23:1095–1103

    Article  CAS  PubMed  Google Scholar 

  75. Garnero P, Gineyts E, Schaffer AV, Seaman J, Delmas PD (1998) Measurement of urinary excretion of nonisomerized an beta-isomerized forms of type I collagen breakdown products to monitor the effects of the bisphosphonate zoledronate in Paget’s disease. Arthritis Rheum 41:354–360

    Article  CAS  PubMed  Google Scholar 

  76. Nagaoka H, Terajima M, Yamada S, Azuma Y, Chida T, Yamauchi M (2014) Alfacalcidol enhances collagen quality in ovariectomized rat bones. J Orthop Res 32:1030–1036

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  77. Saito M, Grynpas MD, Burr DB, Allen MR, Smith SY, Doyle N, Amizuka N, Hasegawa T, Kida Y, Marumo K, Saito H (2015) Treatment with eldecalcitol positively affects mineralization, microdamage, and collagen crosslinks in primate bone. Bone 73:8–15

    Article  CAS  PubMed  Google Scholar 

  78. Nyman JS, Ni Q, Nicolella DP, Wang X (2008) Measurements of mobile and bound water by nuclear magnetic resonance correlate with mechanical properties of bone. Bone 42:193–199

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  79. Nyman JS, Roy A, Shen X, Acuna RL, Tyler JH, Wang X (2006) The influence of water removal on the strength and toughness of cortical bone. J Biomech 39:931–938

    Article  PubMed Central  PubMed  Google Scholar 

  80. Gallant MA, Brown DM, Hammond M, Wallace JM, Du J, Deymier-Black AC, Almer JD, Stock SR, Allen MR, Burr DB (2014) Bone cell-independent benefits of raloxifene on the skeleton: a novel mechanism for improving bone material properties. Bone 61:191–200

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  81. Luo Q, Nakade R, Dong X, Rong Q, Wang X (2011) Effect of mineral–collagen interfacial behavior on the microdamage progression in bone using a probabilistic cohesive finite element model. J Mech Behav Biomed Mater 4:943–952

    Article  CAS  PubMed  Google Scholar 

  82. Garnero P, Cloos P, Sornay-Rendu E, Qvist P, Delmas PD (2002) Type I collagen racemization and isomerization and the risk of fracture in postmenopausal women: the OFELY prospective study. J Bone Miner Res 17:826–833

    Article  CAS  PubMed  Google Scholar 

  83. Hoshino H, Takahashi M, Kushida K, Ohishi T, Inoue T (1999) The relationships between the degree of beta-isomerization of type I collagen degradation products in the urine and aging, menopause and osteoporosis with fractures. Osteoporos Int 9:405–409

    Article  CAS  PubMed  Google Scholar 

  84. Bauer DC, Garnero P, Litwack S, Cauley JA, Ensrud K, Eastell R, Orwoll E (2010) Type I collagen isomerization (alpha/beta CTX ratio) and the risk of new vertebral fracture in men: a prospective study. J Bone Miner Res 25(Suppl 1):1024

    Google Scholar 

  85. Byrjalsen I, Leeming DJ, Qvist P, Christiansen C, Karsdal MA (2008) Bone turnover and bone collagen maturation in osteoporosis: effects of antiresorptive therapies. Osteoporos Int 19:339–348

    Article  CAS  PubMed  Google Scholar 

  86. Garnero P, Bauer D, Mareau E, Bilezikian JP, Greenspan SL, Rosen C, Black D (2008) Effects of PTH and alendronate on type I collagen isomerization in postmenopausal women with osteoporosis: the PaTH study. J Bone Miner Res 23:1442–1448

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  87. Kauppila S, Jukkola A, Melkko J, Risteli L, Turpeeniemi-Hujanen T, Vuorinen K, Risteli J (2001) Aminoterminal propeptide of the alpha1-homotrimer variant of human type I procollagen (hotPINP) in malignant pleural effusion. Anticancer Res 21(4A):2293–2296

    CAS  PubMed  Google Scholar 

Download references

Conflict of interest

Patrick Garnero does not have any conflict of interest to disclose.

Human and Animal Rights and Informed Consent

All studies reviewed in this paper have been performed following regulatory requirements for human and animal rights and informed consent statements have been obtained from each patient.

Author information

Authors and Affiliations

  1. INSERM UMR 1033, Lyon, France

    Patrick Garnero

Authors
  1. Patrick Garnero
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Patrick Garnero.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Garnero, P. The Role of Collagen Organization on the Properties of Bone. Calcif Tissue Int 97, 229–240 (2015). https://doi.org/10.1007/s00223-015-9996-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00223-015-9996-2

Keywords

Search

Navigation