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Hyperosteoidosis and Hypermineralization in the Same Bone: Bone Tissue Analyses in a Boy with a Homozygous BMP1 Mutation

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Abstract

Recently, homozygous mutations in BMP1 were identified as a cause of bone fragility in children with high areal bone mineral density. We examined iliac bone tissue from a 12-year-old boy with a homozygous mutation that leads to a p.Gly12Arg change in the signal peptide of BMP1, an enzyme that cleaves C-propeptide off the procollagen type I molecule. Histomorphometric analyses revealed marked hyperosteoidosis, with osteoid volume per bone volume at approximately 11 SD above the mean value for controls. At the same time, quantitative backscattered electron imaging showed drastic hypermineralization of mineralized bone matrix. CaPeak, representing the most frequently observed calcium content of mineralized matrix in trabecular bone, was 9 SD above the mean for the control population, corresponding to a 21 % higher calcium content in the patient specimen than in the average control sample. These results are similar to those that were previously reported in an individual who had a mutation in the C-propeptide cleavage site of procollagen type I. It thus appears that disturbed C-propeptide cleavage impairs mineralization in two ways: first, the onset of mineralization is delayed, leading to an increased amount of unmineralized osteoid, and second, once mineralization starts, too much mineral is incorporated into the bone matrix, resulting in hypermineralization.

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Acknowledgement

All procedures were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000. Informed consent was obtained from the legal guardians. We thank Mark Lepik for preparation of the figures. We additionally thank Prof. Dr. Troebs from Marienhospital Herne for taking the bone biopsy during surgery. Frank Rauch received support from the Chercheur-Boursier Clinicien program of the Fonds de Recherche du Québec-Santé. In addition, this study was supported by the Shriners of North America, and Paul Roschger and Klaus Klaushofer were supported by the AUVA (Research Funds of the Austrian Workers Compensation Board), and the WGKK (Viennese Sickness Insurance Funds).

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Authors and Affiliations

  1. Department of Pediatrics and Adolescent Medicine, University Hospital Cologne, Kerpenerstr. 62, 50924, Cologne, Germany

    Heike Hoyer-Kuhn, Oliver Semler & Eckhard Schoenau

  2. 1st Medical Department, Ludwig Boltzmann Institute of Osteology at the Hanusch Hospital of WGKK and AUVA Trauma Center Meidling, Hanusch Hospital, Heinrich Collin-Str. 30, 1140, Vienna, Austria

    Paul Roschger & Klaus Klaushofer

  3. Shriners Hospital for Children, McGill University, 1529 Cedar Avenue, Montreal, QC, H3G 1A6, Canada

    Frank Rauch

Authors
  1. Heike Hoyer-Kuhn
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  2. Oliver Semler
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  3. Eckhard Schoenau
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  4. Paul Roschger
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  5. Klaus Klaushofer
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  6. Frank Rauch
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Correspondence to Heike Hoyer-Kuhn.

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The authors declare that they have no conflict of interest.

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Hoyer-Kuhn, H., Semler, O., Schoenau, E. et al. Hyperosteoidosis and Hypermineralization in the Same Bone: Bone Tissue Analyses in a Boy with a Homozygous BMP1 Mutation. Calcif Tissue Int 93, 565–570 (2013). https://doi.org/10.1007/s00223-013-9799-2

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  • DOI: https://doi.org/10.1007/s00223-013-9799-2

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