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Skeletal mineralization defects in adult hypophosphatasia—a clinical and histological analysis

Osteoporosis International volume 22, pages 2667–2675 (2011)Cite this article

Abstract

Summary

Histomorphometry and quantitative backscattered electron microscopy of iliac crest biopsies from patients with adult hypophosphatasia not only confirmed the expected enrichment of non-mineralized osteoid, but also demonstrated an altered trabecular microarchitecture, an increased number of osteoblasts, and an impaired calcium distribution within the mineralized bone matrix.

Introduction

Adult hypophosphatasia is an inherited disorder of bone metabolism caused by inactivating mutations of the ALPL gene, encoding tissue non-specific alkaline phosphatase. While it is commonly accepted that the increased fracture risk of the patients is the consequence of osteomalacia, there are only few studies describing a complete histomorphometric analysis of bone biopsies from affected individuals. Therefore, we analyzed iliac crest biopsies from eight patients and set them in direct comparison to biopsies from healthy donors or from individuals with other types of osteomalacia.

Methods

Histomorphometric analysis was performed on non-decalcified sections stained either after von Kossa/van Gieson or with toluidine blue. Bone mineral density distribution was quantified by backscattered electron microscopy.

Results

Besides the well-documented enrichment of non-mineralized bone matrix in individuals suffering from adult hypophosphatasia, our histomorphometric analysis revealed alterations of the trabecular microarchitecture and an increased number of osteoblasts compared to healthy controls or to individuals with other types of osteomalacia. Moreover, the analysis of the mineralized bone matrix revealed significantly decreased calcium content in patients with adult hypophosphatasia.

Conclusions

Taken together, our data show that adult hypophosphatasia does not solely result in an enrichment of osteoid, but also in a considerable degradation of bone quality, which might contribute to the increased fracture risk of the affected individuals.

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Acknowledgments

The authors thank Ms. Olga Winter for excellent technical assistance in preparing the samples for qualitative and quantitative histomorphometry.

Conflicts of interest

None.

Author information

Affiliations

  1. Department of Osteology and Biomechanics, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246, Hamburg, Germany

    F. Barvencik, F. Timo Beil, M. Gebauer, B. Busse, T. Koehne, S. Seitz, P. Pogoda, T. Schinke & M. Amling

  2. Department of Orthopaedics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

    F. Timo Beil & S. Seitz

  3. Materials Sciences Division, Lawrence Berkeley National Laboratory, University of California, Berkeley, USA

    B. Busse

  4. Institute of Bone Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

    J. Zustin

  5. Department of Trauma-, Hand- and Reconstructive Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

    P. Pogoda

Authors
  1. F. Barvencik
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  2. F. Timo Beil
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  9. T. Schinke
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  10. M. Amling
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Corresponding author

Correspondence to M. Amling.

Additional information

Florian Barvencik and Frank Timo Beil contributed equally to this work and therefore share first authorship.

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Barvencik, F., Beil, F.T., Gebauer, M. et al. Skeletal mineralization defects in adult hypophosphatasia—a clinical and histological analysis. Osteoporos Int 22, 2667–2675 (2011). https://doi.org/10.1007/s00198-011-1528-y

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  • DOI: https://doi.org/10.1007/s00198-011-1528-y

Keywords

  • Alkaline phosphatase
  • Histomorphometry
  • Osteoid
  • Osteomalacia
  • qBEI