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Evidence that Abnormal High Bone Mineralization in Growing Children with Osteogenesis Imperfecta is not Associated with Specific Collagen Mutations

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Abstract

Osteogenesis imperfecta type I (OI-I) represents the mildest form of OI. The collagen I mutations underlying the disorder can be classified as quantitative mutations that lead to formation of a decreased amount of normal collagen or qualitative mutations where structurally aberrant collagen chains are generated. However, the phenotypic consequences of a particular mutation are not well understood. Transiliac bone biopsies from 19 young OI-I patients (age range 2.0–14.1 years) and 19 age-matched controls were used to assess bone histomorphometric parameters and bone mineralization density distribution, measured by quantitative backscattered electron imaging. Thirteen of the OI-I patients were affected by quantitative and six patients by qualitative mutations. Compared to age-matched controls, iliac bone samples in the OI group were smaller and had thinner cortices and less trabecular bone. Resorption parameters were similar between groups, whereas surface-based parameters of bone formation were considerably higher in OI patients than in controls with the exception of bone formation rate per osteoblast surface, which was reduced in OI. Backscattered electron imaging revealed a higher mean mineralization density (+7%, P < 0.001) in OI-I patients than in age-matched controls, which was accompanied by a reduced heterogeneity of mineralization (−13%, P < 0.001). However, the increase of mean degree of mineralization in OI did not exceed the average level of normal adult bone. No differences were found between the two mutation types. In summary, the tissue- and material-level abnormalities found in OI-I (low bone mass and increased mineral content of the matrix) seem to be independent of the collagen mutations.

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Acknowledgements

We thank G. Dinst, Ph. Messmer, D. Gabriel, and S. Thon for careful sample preparations and qBEI measurements at the bone material laboratory of the Ludwig-Boltzmann-Institute of Osteology (Vienna, Austria) and Rose Travers for histomorphometric analyses at the Genetics Unit of the Shriners Hospital (Montreal, Canada). This study was supported by the AUVA (Research Funds of the Austrian Workers Compensation Board), by the WGKK (Viennese Sickness Insurance Funds), the FWF Project (P16880-B13), and the Shriners of North America. F. R. is a Chercheur-Boursier Clinicien of the Fonds de la Recherche en Santé du Québec.

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Authors and Affiliations

  1. Ludwig Boltzmann Institute of Osteology at the Hanusch Hospital of WGKK and AUVA Trauma Center Meidling, 4th Medical Department, Hanusch Hospital, Heinrich Collin Str. 30, 1140, Vienna, Austria

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

  2. Ludwig Boltzmann Institute of Osteology, UKH Meidling, Kundratstrasse 37, A-1120, Vienna, Austria

    Nadja Fratzl-Zelman

  3. Genetics Unit, Shriners Hospital for Children and McGill University, H3G 1A6, Montreal, Quebec, Canada

    Francis H. Glorieux & Frank Rauch

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  1. Paul Roschger
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  2. Nadja Fratzl-Zelman
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  3. Barbara M. Misof
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  4. Francis H. Glorieux
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  5. Klaus Klaushofer
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  6. Frank Rauch
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Correspondence to Nadja Fratzl-Zelman.

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Roschger, P., Fratzl-Zelman, N., Misof, B.M. et al. Evidence that Abnormal High Bone Mineralization in Growing Children with Osteogenesis Imperfecta is not Associated with Specific Collagen Mutations. Calcif Tissue Int 82, 263–270 (2008). https://doi.org/10.1007/s00223-008-9113-x

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  • DOI: https://doi.org/10.1007/s00223-008-9113-x

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