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Bone mass and mineralization in osteogenesis imperfecta

Knochenmasse und Mineralgehalt in Osteogenesis imperfecta

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Summary

The main clinical features of osteogenesis imperfecta (OI) are low bone mass and high bone fragility. While the decrease in bone mass is generally regarded as an indicator of disease severity, bone fragility appears as the hallmark of the disorder. Bone has a multiscale hierarchical structural organization and is optimized to resist to fractures. In OI, modifications at the molecular level affect the total mechanical integrity of the bone. A specific characteristic in OI is that the bone matrix is abnormally high mineralized independently of the underlying mutation or clinical severity. The increased matrix mineralization affects bone material quality, leading to increased stiffness and brittleness and making bone prone to fractures. The purpose of this review is to give further insights on bone matrix mineralization in OI and to discuss advantages and pitfalls of invasive and noninvasive imaging techniques.

Zusammenfassung

Die wichtigsten klinischen Merkmale der Glasknochenkrankheit (Osteogenesis Imperfecta, OI) sind eine geringe Knochenmasse und eine erhöhte Knochenbrüchigkeit. Während die verminderte Knochenmasse als Indikator des Schweregrads dient, ist die Fragilität des Knochens ein allgemeines Merkmal der Erkrankung. Knochen ist bis in den Nanometerbereich hierarchisch so aufgebaut, dass er Brüchen möglichst widersteht. Bei OI wirken sich molekulare Veränderungen auf die mechanische Integrität des Knochens aus: so ist die Kollagenmatrix in OI, unabhängig von der Mutation und vom klinischen Schweregrad, stärker mineralisiert als normal, wodurch das Knochenmaterial steifer und vermutlich auch spröder wird. Dieser Artikel fasst den Stand des Wissens zur Mineralisierung der Knochenmatrix in OI zusammen und diskutiert die Möglichkeiten und Probleme von invasiven und nicht-invasiven Abbildungstechniken.

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References

  1. Rauch F, Glorieux FH. Osteogenesis imperfecta. Lancet. 2004;363:1377–85.

    Article  CAS  PubMed  Google Scholar 

  2. Forlino A, Cabral WA, Barnes AM, Marini JC. New perspectives on osteogenesis imperfecta. Nat Rev Endocrinol. 2011;7:540–57.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  3. Braga V, Gatti D, Rossini M, Colapietro F, Battaglia E, Viapiana O, Adami S. Bone turnover markers in patients with osteogenesis imperfecta. Bone. 2004;34:1013–6.

    Article  CAS  PubMed  Google Scholar 

  4. Fratzl P, Gupta H, Paschalis E, Roschger P. Structure and mechanical quality of the collagen-mineral nano-composite in bone. J Mater Chem 2004;14:2115–23.

    Article  CAS  Google Scholar 

  5. Bouxsein ML, Seeman E. Quantifying the material and structural determinants of bone strength. Best Pract Res Clin Rheumatol. 2009;23:741–53.

    Article  PubMed  Google Scholar 

  6. Wagermaier W, Klaushofer K, Fratzl P. Fragility of bone material controlled by internal interfaces. Calcif Tissue Int. 2015 Mar 14 [epub ahead of print].

  7. Bouxsein ML. Technology insight: noninvasive assessment of bone strength in osteoporosis. Nat Clin Pract Rheumatol. 2008;4:310–8.

    Article  PubMed  Google Scholar 

  8. Fratzl P, Roschger P, Fratzl-Zelman N, Paschalis EP, Phipps R, Klaushofer K. Evidence that treatment with risedronate in women with postmenopausal osteoporosis affects bone mineralization and bone volume. Calcif Tissue Int. 2007;81:73–80.

    Article  CAS  PubMed  Google Scholar 

  9. Gatti D, Colapietro F, Fracassi E, Sartori E, Antoniazzi F, Braga V, Rossini M, Adami S. The volumetric bone density and cortical thickness in adult patients affected by osteogenesis imperfecta. J Clin Densitom. 2003;6:173–7.

    Article  PubMed  Google Scholar 

  10. Rauch F, Land C, Cornibert S, Schoenau E, Glorieux FH. High and low density in the same bone: a study on children and adolescents with mild osteogenesis imperfecta. Bone. 2005;37:634–41.

    Article  PubMed  Google Scholar 

  11. Folkestad L, Hald JD, Hansen S, Gram J, Langdahl B, Abrahamsen B, Brixen K. Bone geometry, density, and microarchitecture in the distal radius and tibia in adults with osteogenesis imperfecta type I assessed by high-resolution pQCT. J Bone Miner Res. 2012;27:1405–12.

    Article  PubMed  Google Scholar 

  12. Adams JE. Quantitative computed tomography. Eur J Radiol. 2009;71:415–24.

    Article  PubMed  Google Scholar 

  13. Rauch F. Watching bone cells at work: what we can see from bone biopsies. Pediatr Nephrol. 2006;21:457–62.

    Article  PubMed  Google Scholar 

  14. Rauch F, Travers R, Parfitt AM, Glorieux FH. Static and dynamic bone histomorphometry in children with osteogenesis imperfecta. Bone. 2000;26:581–9.

    Article  CAS  PubMed  Google Scholar 

  15. Roschger P, Fratzl-Zelman N, Misof BM, Glorieux FH, Klaushofer K, Rauch F. Evidence that abnormal high bone mineralization in growing children with osteogenesis imperfecta is not associated with specific collagen mutations. Calcif Tissue Int. 2008;82:263–70.

    Article  CAS  PubMed  Google Scholar 

  16. Roschger P, Paschalis EP, Fratzl P, Klaushofer K. Bone mineralization density distribution in health and disease. Bone. 2008;42:456–66.

    Article  CAS  PubMed  Google Scholar 

  17. Fratzl-Zelman N, Roschger P, Misof BM, Pfeffer S, Glorieux FH, Klaushofer K, Rauch F. Normative data on mineralization density distribution in iliac bone biopsies of children, adolescents and young adults. Bone. 2009;44:1043–8.

    Article  CAS  PubMed  Google Scholar 

  18. Shapiro JR, McCarthy EF, Rossiter K, Ernest K, Gelman R, Fedarko N, Santiago HT, Bober M. The effect of intravenous pamidronate on bone mineral density, bone histomorphometry, and parameters of bone turnover in adults with type IA osteogenesis imperfecta. Calcif Tissue Int. 2003;72:103–12.

    Article  CAS  PubMed  Google Scholar 

  19. Ben Amor M, Rauch F, Monti E, Antoniazzi F. Osteogenesis imperfecta. Pediatr Endocrinol Rev. 2013;10(Suppl. 2):397–405.

    PubMed  Google Scholar 

  20. Patel RM, Nagamani SC, Cuthbertson D, Campeau PM, Krischer JP, Shapiro JR, Steiner RD, Smith PA, Bober MB, Byers PH, Pepin M, Durigova M, Glorieux FH, Rauch F, Lee BH, Hart T, Sutton VR. A cross-sectional multicenter study of osteogenesis imperfecta in North America—results from the linked clinical research centers. Clin Genet. 2015;87(2):133–40.

  21. Kocijan R, Muschitz C, Fratzl-Zelman N, Haschka J, Dimai HP, Trubrich A, Bittighofer C, Resch H. Femoral geometric parameters and BMD measurements by DXA in adult patients with different types of osteogenesis imperfecta. Skeletal Radiol. 2013;42:187–94.

    Article  PubMed  Google Scholar 

  22. Wekre LL, Eriksen EF, Falch JA. Bone mass, bone markers and prevalence of fractures in adults with osteogenesis imperfecta. Arch Osteoporos. 2011;6:31–8.

    Article  PubMed Central  PubMed  Google Scholar 

  23. Gatti D, Viapiana O, Lippolis I, Braga V, Prizzi R, Rossini M, Adami S. Intravenous bisphosphonate therapy increases radial width in adults with osteogenesis imperfecta. J Bone Miner Res. 2005;20:1323–6.

    Article  CAS  PubMed  Google Scholar 

  24. Chevrel G, Schott AM, Fontanges E, Charrin JE, Lina-Granade G, Duboeuf F, Garnero P, Arlot M, Raynal C, Meunier PJ. Effects of oral alendronate on BMD in adult patients with osteogenesis imperfecta: a 3-year randomized placebo-controlled trial. J Bone Miner Res. 2006;21:300–6.

    Article  CAS  PubMed  Google Scholar 

  25. Lindahl K, Langdahl B, Ljunggren O, Kindmark A. Treatment of osteogenesis imperfecta in adults. Eur J Endocrinol. 2014;171:R79–90.

    Article  CAS  PubMed  Google Scholar 

  26. Traub W, Arad T, Vetter U, Weiner S. Ultrastructural studies of bones from patients with osteogenesis imperfecta. Matrix Biol. 1994;14:337–45.

    Article  CAS  PubMed  Google Scholar 

  27. Grabner B, Landis WJ, Roschger P, Rinnerthaler S, Peterlik H, Klaushofer K, Fratzl P. Age- and genotype-dependence of bone material properties in the osteogenesis imperfecta murine model (oim). Bone. 2001;29:453–7.

    Article  CAS  PubMed  Google Scholar 

  28. 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. 2014;29:1392–401.

    Article  PubMed Central  PubMed  Google Scholar 

  29. Rauch F, Lalic L, Roughley P, Glorieux FH. Relationship between genotype and skeletal phenotype in children and adolescents with osteogenesis imperfecta. J Bone Miner Res. 2010;25:1367–74.

    CAS  PubMed  Google Scholar 

  30. Ben Amor IM, Roughley P, Glorieux FH, Rauch F. Skeletal clinical characteristics of osteogenesis imperfecta caused by haploinsufficiency mutations in COL1A1. J Bone Miner Res. 2013;28:2001–7.

    Article  CAS  PubMed  Google Scholar 

  31. Marini JC, Forlino A, Cabral WA, Barnes AM, San Antonio JD, Milgrom S, Hyland JC, Korkko J, Prockop DJ, De Paepe A, Coucke P, Symoens S, Glorieux FH, Roughley PJ, Lund AM, Kuurila-Svahn K, Hartikka H, Cohn DH, Krakow D, Mottes M, Schwarze U, Chen D, Yang K, Kuslich C, Troendle J, Dalgleish R, Byers PH. Consortium for osteogenesis imperfecta mutations in the helical domain of type I collagen: regions rich in lethal mutations align with collagen binding sites for integrins and proteoglycans. Hum Mutat. 2007;28:209–21.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  32. Weber M, Roschger P, Fratzl-Zelman N, Schoberl T, Rauch F, Glorieux FH, Fratzl P, Klaushofer K. Pamidronate does not adversely affect bone intrinsic material properties in children with osteogenesis imperfecta. Bone. 2006;39:616–22.

    Article  CAS  PubMed  Google Scholar 

  33. Fratzl-Zelman N, Morello R, Lee B, Rauch F, Glorieux FH, Misof BM, Klaushofer K, Roschger P. CRTAP deficiency leads to abnormally high bone matrix mineralization in a murine model and in children with osteogenesis imperfecta type VII. Bone. 2010;46:820–6.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  34. Marini JC, Reich A, Smith SM. Osteogenesis imperfecta due to mutations in non-collagenous genes: lessons in the biology of bone formation. Curr Opin Pediatr. 2014;26:500–7.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  35. Fratzl-Zelman N, Schmidt I, Roschger P, Roschger A, Glorieux FH, Klaushofer K, Wagermaier W, Rauch F, Fratzl P. Unique micro- and nano-scale mineralization pattern of human osteogenesis imperfecta type VI bone. Bone. 2015;73:233–41

  36. Lindahl K, Barnes AM, Fratzl-Zelman N, Whyte MP, Hefferan TE, Makareeva E, Brusel M, Yaszemski MJ, Rubin CJ, Kindmark A, Roschger P, Klaushofer K, McAlister WH, Mumm S, Leikin S, Kessler E, Boskey AL, Ljunggren O, Marini JC. COL1 C-propeptide cleavage site mutations cause high bone mass osteogenesis imperfecta. Hum Mutat. 2011;32:598–609.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  37. Hoyer-Kuhn H, Semler O, Schoenau E, Roschger P, Klaushofer K, Rauch F. Hyperosteoidosis and hypermineralization in the same bone: bone tissue analyses in a boy with a homozygous BMP1 mutation. Calcif Tissue Int. 2013;93:565–70.

    Article  CAS  PubMed  Google Scholar 

  38. Palomo T, Al-Jallad H, Moffatt P, Glorieux FH, Lentle B, Roschger P, Klaushofer K, Rauch F. Skeletal characteristics associated with homozygous and heterozygous WNT1 mutations. Bone. 2014;67:63–70.

    Article  CAS  PubMed  Google Scholar 

  39. Fahiminiya S, Majewski J, Al-Jallad H, Moffatt P, Mort J, Glorieux FH, Roschger P, Klaushofer K, Rauch F. Osteoporosis caused by mutations in PLS3: clinical and bone tissue characteristics. J Bone Miner Res. 2014;29:1805–14.

    Article  CAS  PubMed  Google Scholar 

  40. Jones SJ, Glorieux FH, Travers R, Boyde A. The microscopic structure of bone in normal children and patients with osteogenesis imperfecta: a survey using backscattered electron imaging. Calcif Tissue Int. 1999;64:8–17.

    Article  CAS  PubMed  Google Scholar 

  41. Boyde A, Travers R, Glorieux FH, Jones SJ. The mineralization density of iliac crest bone from children with osteogenesis imperfecta. Calcif Tissue Int. 1999;64:185–90.

    Article  CAS  PubMed  Google Scholar 

  42. Fratzl-Zelman N, Schmidt I, Roschger P, Glorieux FH, Klaushofer K, Fratzl P, Rauch F, Wagermaier W. Mineral particle size in children with osteogenesis imperfecta type I is not increased independently of specific collagen mutations. Bone. 2014;60:122–8.

    Article  CAS  PubMed  Google Scholar 

  43. Fratzl P, Paris O, Klaushofer K, Landis WJ. Bone mineralization in an osteogenesis imperfecta mouse model studied by small-angle X-ray scattering. J Clin Invest. 1996;97:396–402.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  44. Vanleene M, Porter A, Guillot PV, Boyde A, Oyen M, Shefelbine S. Ultra-structural defects cause low bone matrix stiffness despite high mineralization in osteogenesis imperfecta mice. Bone. 2012;50:1317–23.

    Article  PubMed Central  PubMed  Google Scholar 

  45. Patsch JM, Burghardt AJ, Kazakia G, Majumdar S. Noninvasive imaging of bone microarchitecture. Ann N Y Acad Sci. 2011;1240:77–87.

    Article  PubMed Central  PubMed  Google Scholar 

  46. Nishiyama KK, Shane E. Clinical imaging of bone microarchitecture with HR-pQCT. Curr Osteoporos Rep. 2013;11:147–55.

    Article  PubMed Central  PubMed  Google Scholar 

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Acknowledgments

The authors are very grateful to Prof. Dr. Peter Fratzl (Max-Planck Institute of Colloids and Interfaces, Golm, Germany) for the long-standing cooperation and the helpful discussion during the preparation of this manuscript. The work at the Ludwig Boltzmann Institute of Osteology was supported by the AUVA (Austrian Social Insurance for Occupational Risk) and the WGKK (Social Health Insurance Vienna).

Conflict of interest

All authors state that they have no conflicts of interest.

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Authors and Affiliations

  1. Ludwig Boltzmann Institute of Osteology, Hanusch Hospital of WGKK and AUVA Trauma Centre Meidling 1st Med. Dept. Hanusch Hospital, Heinrich Collin Str. 30, 1140, Vienna, Austria

    Nadja Fratzl-Zelman PhD,  Barbara M. Misof PhD,  Klaus Klaushofer MD &  Paul Roschger PhD

  2. Ludwig Boltzmann Institute of Osteology, Trauma Center Meidling, Kundratstr. 37, A-1120, Vienna, Austria

    Nadja Fratzl-Zelman PhD

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  1. Nadja Fratzl-Zelman PhD
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  2. Barbara M. Misof PhD
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Correspondence to Nadja Fratzl-Zelman PhD.

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Fratzl-Zelman, N., Misof, B., Klaushofer, K. et al. Bone mass and mineralization in osteogenesis imperfecta. Wien Med Wochenschr 165, 271–277 (2015). https://doi.org/10.1007/s10354-015-0369-2

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  • DOI: https://doi.org/10.1007/s10354-015-0369-2

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