Bone material properties in actively bone-forming trabeculae in postmenopausal women with osteoporosis after three years of treatment with once-yearly Zoledronic acid

Authors

  • Sonja Gamsjaeger,

    1. Ludwig Boltzmann Institute of Osteology, Hanusch Hospital of WGKK (Viennese Sickness Insurance Funds) and AUVA (Austrian Social Insurance for Occupational Risks) Trauma Center Meidling, 4th Medical Department, Hanusch Hospital, Vienna, Austria
    Search for more papers by this author
  • Birgit Buchinger,

    1. Ludwig Boltzmann Institute of Osteology, Hanusch Hospital of WGKK (Viennese Sickness Insurance Funds) and AUVA (Austrian Social Insurance for Occupational Risks) Trauma Center Meidling, 4th Medical Department, Hanusch Hospital, Vienna, Austria
    Search for more papers by this author
  • Elizabeth Zwettler,

    1. Ludwig Boltzmann Institute of Osteology, Hanusch Hospital of WGKK (Viennese Sickness Insurance Funds) and AUVA (Austrian Social Insurance for Occupational Risks) Trauma Center Meidling, 4th Medical Department, Hanusch Hospital, Vienna, Austria
    Search for more papers by this author
  • Robert Recker,

    1. Osteoporosis Research Center, Creighton University, Omaha, NE, USA
    Search for more papers by this author
  • Dennis Black,

    1. Division of Clinical Trials and Multicenter Studies, University of California, San Francisco, San Francisco, CA, USA
    Search for more papers by this author
  • Juerg A Gasser,

    1. Novartis Institutes for BioMedical Research, Basel, Switzerland
    Search for more papers by this author
  • Erik F Eriksen,

    1. Hormonlaboratoriet, AUS Aker Universitetssykehus Trondheimsveien, Oslo, Norway
    Search for more papers by this author
  • Klaus Klaushofer,

    1. Ludwig Boltzmann Institute of Osteology, Hanusch Hospital of WGKK (Viennese Sickness Insurance Funds) and AUVA (Austrian Social Insurance for Occupational Risks) Trauma Center Meidling, 4th Medical Department, Hanusch Hospital, Vienna, Austria
    Search for more papers by this author
  • Eleftherios P Paschalis

    Corresponding author
    1. Ludwig Boltzmann Institute of Osteology, Hanusch Hospital of WGKK (Viennese Sickness Insurance Funds) and AUVA (Austrian Social Insurance for Occupational Risks) Trauma Center Meidling, 4th Medical Department, Hanusch Hospital, Vienna, Austria
    2. University General Hospital “Attikon,” National and Kapodistrian University of Athens, School of Medicine, 1st Department of Orthopaedic Surgery, Athens, Greece
    • Ludwig Boltzmann Institute of Osteology, Hanusch Krankenhaus, Heinrich Collin Street 30, A-1140 Vienna, Austria.
    Search for more papers by this author

Abstract

Zoledronic acid (ZOL), a third-generation aminobisphosphonate, showed pronounced antifracture efficacy in a phase III clinical trial [Health Outcomes and Reduced Incidence with Zoledronic Acid Once Yearly—Pivotal Fracture Trial (HORIZON-PFT)] when administered yearly (5-mg infusions of ZOL), producing significant reductions in morphometric vertebral, clinical vertebral, hip, and nonvertebral fractures by 70%, 77%, 41%, and 25%, respectively, over a 3-year period. The purpose of this study was to analyze the biopsies obtained during the HORIZON clinical trial (152 patients, 82 ZOL and 70 placebo) by means of Raman microspectroscopy (a vibrational spectroscopic technique capable of analyzing undecalcified bone tissue with a spatial resolution of approximately 0.6 µm) to determine the effect of ZOL therapy on bone material properties (in particular mineral/matrix ratio, lamellar organization, carbonate and proteoglycan (based on spectral identification of glycosaminoglycan) content, and mineral maturity/crystallinity) at similar tissue age (based on the presence of tetracycline double labels). The results indicated that while ZOL administration increased the mineral/matrix ratio compared with placebo, it also resulted in mineral crystallites with a quality profile (based on carbonate content and maturity/crystallinity characteristics) of younger (with respect to tissue age) bone. Since the comparisons between ZOL- and placebo-treated patients were performed at similar tissue age at actively forming bone surfaces, these results suggest that ZOL may be exerting an effect on bone matrix formation in addition to its well-established antiresorptive effect, thereby contributing to its antifracture efficacy. © 2011 American Society for Bone and Mineral Research.

Ancillary