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Ibandronate Increases Sclerostin Levels and Bone Strength in Male Patients with Idiopathic Osteoporosis

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Abstract

The pathomechanism of male idiopathic osteoporosis (MIO) differs from postmenopausal osteoporosis with regard to alterations in osteoblast activity. We evaluated intravenous ibandronate (IBN) in 25 MIO patients with fragility fractures in a prospective, monocentric, single-arm, and open-label study for 24 months. The impact and changes of sclerostin (Scl), Dickkopf-1 (DKK-1), CTX, and PINP were examined. Additionally, volumetric cortical, trabecular and areal bone mineral density (BMD), trabecular bone score (TBS), and finite element analyses (FEA) were evaluated. Compared to baseline, median Scl levels were increased after 1 month (Δ 121 %, p < 0.0001) and remained elevated for 12 months. DKK-1 decreased (p < 0.001) to a lesser extent until month 9 with values comparable to baseline at study endpoint. Early changes (baseline–month 1) of Scl negatively correlated with early changes of DKK-1 (−0.72), CTX (−0.82), and PINP (−0.55; p < 0.005 for all). The overall changes over the 24 months study period of Scl negatively correlated with decreased CTX (−0.32) and DKK-1 levels (−0.57, p < 0.0001 for both); CTX and PINP changes positively correlated at each time point (p < 0.001). Volumetric hip BMD increased by 12 and 18 %, respectively (p < 0.0001 for both). Cross-sectional moment of inertia and section modulus for total hip significantly improved (p < 0.05 for all). Areal BMD at total hip, spine, and TBS increased. FEA displayed an increase in bone strength both in the hip (17 %) and vertebrae (13 %, all p < 0.0001) at anatomical sites susceptible for fragility fracture. IBN increases Scl and improves cortical and trabecular bone strength with early and ongoing vigorous suppression of bone resorption.

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Acknowledgements

The authors cordially thank Dr. Heike von Krempelhuber at Tutzing/Germany for assistance in editing the manuscript, Sabine Klauss and Xenia Steiner at Ulm/Germany for graphic design of the figures. The authors further acknowledge the work of the staff of the central laboratory and of the Department of Diagnostic and Interventional Radiology at St. Vincent Hospital Vienna, Austria. QCT DICOM data were calculated without knowledge of the study protocol by Dr. Wolfram Timm at Kiel/Germany. FEA calculations were performed by Dr. Enrico Dall’Ara at the Institute of Lightweight Design and Structural Biomechanics, University of Technology, Vienna, Austria. TBS scores were calculated without knowledge of the study protocol by Prf. Didier Hans at Lausanne/CH.

Conflict of interest

Christian Muschitz has received speaker honoraria from Amgen, Novartis, Servier, Eli Lilly, Nycomed/Takeda, and has received educational grants/research support from the Austrian Society for Bone and Mineral Research, Roche Austria, Eli Lilly Austria, and Amgen Austria. Heinrich Resch has received speaker honoraria from Amgen, Novartis, Servier, Eli Lilly, Nycomed/Takeda, Merck (MSD), and has received educational grants/research support from Eli Lilly and Roche Austria. Peter Pietschmann has received research support and/or honoraria from Amgen GmbH, Eli Lilly GmbH, Fresenius Kabi Austria GmbH, Merck, Sharp and Dohme GmbH, Novartis Pharma, Nycomed Pharma, Roche Austria, Servier Austria, Sanofi-Austria, and Sinapharm. Karin Amrein reports scientific support from Fresenius Kabi Austria. Dieter Pahr is the owner of a consultancy company for FEA calculations and has received a fee for the QCT segmentation, but not for the FEA calculations in this study. Roland Kocijan, Janina M. Patsch, Barbara M. Misof, and Alexandra Kaider have nothing to disclose.

Human and Animal Rights and Informed Consent

This study was planned and conducted according to the Helsinki Declaration of 2000 and was approved by the Ethics Committee of the Medical University of Vienna/Austria (AUT – 25/2006) and by the Ethics Committee of the St. Vincent Hospital Vienna/Austria (EK-Nr: 2006/12). The study was also registered at EudraCT:2006-006692-20. Informed and written consent was obtained from all patients prior to any study related procedure.

Competing interest

This investigator-initiated study was supported by an independent research grant from Roche Austria. Roche Austria was not involved in the study design or had any admission to patient-related data and findings.

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Authors and Affiliations

  1. Medical Department II, St. Vincent Hospital, Academic Teaching Hospital of the Medical University of Vienna, Stumpergasse 13, 1060, Vienna, Austria

    Christian Muschitz, Roland Kocijan & Heinrich Resch

  2. Institute of Lightweight Design and Structural Biomechanics, University of Technology, Vienna, Austria

    Dieter Pahr

  3. Department of Diagnostic Radiology, Medical University of Vienna, Vienna, Austria

    Janina M. Patsch

  4. Division of Endocrinology and Metabolism, Department of Internal Medicine, Medical University of Graz, Graz, Austria

    Karin Amrein

  5. Ludwig Boltzmann Institute of Osteology, Hanusch Hospital of WGKK and AUVA Trauma Center Meidling, 1st Medical Department, Hanusch Hospital, Vienna, Austria

    Barbara M. Misof

  6. Center for Medical Statistics, Informatics and Intelligent Systems, Medical University of Vienna, Vienna, Austria

    Alexandra Kaider

  7. Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria

    Peter Pietschmann

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  1. Christian Muschitz
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  2. Roland Kocijan
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  3. Dieter Pahr
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  4. Janina M. Patsch
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  8. Heinrich Resch
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  9. Peter Pietschmann
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Correspondence to Christian Muschitz.

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Muschitz, C., Kocijan, R., Pahr, D. et al. Ibandronate Increases Sclerostin Levels and Bone Strength in Male Patients with Idiopathic Osteoporosis. Calcif Tissue Int 96, 477–489 (2015). https://doi.org/10.1007/s00223-015-0003-8

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