Osteoporosis International

, Volume 22, Issue 10, pp 2667–2675

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

  • F. Barvencik
  • F. Timo Beil
  • M. Gebauer
  • B. Busse
  • T. Koehne
  • S. Seitz
  • J. Zustin
  • P. Pogoda
  • T. Schinke
  • M. Amling
Original Article

DOI: 10.1007/s00198-011-1528-y

Cite this article as:
Barvencik, F., Beil, F.T., Gebauer, M. et al. Osteoporos Int (2011) 22: 2667. doi:10.1007/s00198-011-1528-y

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.

Keywords

Alkaline phosphataseHistomorphometryOsteoidOsteomalaciaqBEI

Copyright information

© International Osteoporosis Foundation and National Osteoporosis Foundation 2011

Authors and Affiliations

  • F. Barvencik
    • 1
  • F. Timo Beil
    • 1
    • 2
  • M. Gebauer
    • 1
  • B. Busse
    • 1
    • 3
  • T. Koehne
    • 1
  • S. Seitz
    • 1
    • 2
  • J. Zustin
    • 4
  • P. Pogoda
    • 1
    • 5
  • T. Schinke
    • 1
  • M. Amling
    • 1
  1. 1.Department of Osteology and BiomechanicsUniversity Medical Center Hamburg-EppendorfHamburgGermany
  2. 2.Department of OrthopaedicsUniversity Medical Center Hamburg-EppendorfHamburgGermany
  3. 3.Materials Sciences Division, Lawrence Berkeley National LaboratoryUniversity of CaliforniaBerkeleyUSA
  4. 4.Institute of Bone PathologyUniversity Medical Center Hamburg-EppendorfHamburgGermany
  5. 5.Department of Trauma-, Hand- and Reconstructive SurgeryUniversity Medical Center Hamburg-EppendorfHamburgGermany