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
Rauch F, Glorieux FH. Osteogenesis imperfecta. Lancet. 2004;363:1377–85.
Forlino A, Cabral WA, Barnes AM, Marini JC. New perspectives on osteogenesis imperfecta. Nat Rev Endocrinol. 2011;7:540–57.
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.
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.
Bouxsein ML, Seeman E. Quantifying the material and structural determinants of bone strength. Best Pract Res Clin Rheumatol. 2009;23:741–53.
Wagermaier W, Klaushofer K, Fratzl P. Fragility of bone material controlled by internal interfaces. Calcif Tissue Int. 2015 Mar 14 [epub ahead of print].
Bouxsein ML. Technology insight: noninvasive assessment of bone strength in osteoporosis. Nat Clin Pract Rheumatol. 2008;4:310–8.
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.
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.
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.
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.
Adams JE. Quantitative computed tomography. Eur J Radiol. 2009;71:415–24.
Rauch F. Watching bone cells at work: what we can see from bone biopsies. Pediatr Nephrol. 2006;21:457–62.
Rauch F, Travers R, Parfitt AM, Glorieux FH. Static and dynamic bone histomorphometry in children with osteogenesis imperfecta. Bone. 2000;26:581–9.
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.
Roschger P, Paschalis EP, Fratzl P, Klaushofer K. Bone mineralization density distribution in health and disease. Bone. 2008;42:456–66.
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.
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.
Ben Amor M, Rauch F, Monti E, Antoniazzi F. Osteogenesis imperfecta. Pediatr Endocrinol Rev. 2013;10(Suppl. 2):397–405.
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.
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.
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.
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.
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.
Lindahl K, Langdahl B, Ljunggren O, Kindmark A. Treatment of osteogenesis imperfecta in adults. Eur J Endocrinol. 2014;171:R79–90.
Traub W, Arad T, Vetter U, Weiner S. Ultrastructural studies of bones from patients with osteogenesis imperfecta. Matrix Biol. 1994;14:337–45.
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.
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.
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.
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.
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.
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.
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.
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.
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
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.
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.
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.
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.
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.
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.
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.
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.
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.
Patsch JM, Burghardt AJ, Kazakia G, Majumdar S. Noninvasive imaging of bone microarchitecture. Ann N Y Acad Sci. 2011;1240:77–87.
Nishiyama KK, Shane E. Clinical imaging of bone microarchitecture with HR-pQCT. Curr Osteoporos Rep. 2013;11:147–55.
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).
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All authors state that they have no conflicts of interest.
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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
Keywords
- Osteogenesis imperfecta
- Bone mass
- Bone matrix mineralization
- Imaging techniques
- Transiliac bone biopsies