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Short-Term Effects of High-Dose Zoledronic Acid Treatment on Bone Mineralization Density Distribution After Orthotopic Liver Transplantation

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Abstract

Patients with “hepatic” bone disease exhibit increased fracture incidence. The effects on bone material properties, their changes due to orthotopic liver transplantation (OLT), as well as zolendronate (ZOL) treatment have not yet been investigated. We studied bone mineralization density distribution (BMDD) in paired transiliacal biopsies (at and 6 months after OLT) from patients (control CON n = 18, treatment group ZOL n = 21, the latter treated with i.v. ZOL at doses of 4 mg/month) for how bone at the material level was affected by the “hepatic” disease in general, as well as by OLT and ZOL in particular. (1) BMDD parameters at baseline reflected disturbed bone matrix mineralization in “hepatic” bone disease combined with low turnover. Trabecular bone displayed a decrease in mean and most frequent calcium concentration (CaMEAN −2.9% and CaPEAK −2.8%, respectively; both P < 0.001), increased heterogeneity of mineralization (CaWIDTH +12.2%, P = 0.01), and increased percentage of bone areas with low mineralization (CaLOW +32.4%, P = 0.02) compared to normal; however, there were no differences compared to cortical bone. (2) Six months after OLT, ZOL-treated trabecular bone displayed reduced CaLOW (−32.0%, P = 0.047), cortical bone increased CaMEAN (+4.2%, P = 0.009), increased CaPEAK (+3.3%, P = 0.040), and decreased CaLOW (−55.7, P = 0.038) compared to CON and increased CaMEAN compared to baseline (+1.9, P = 0.032) without any signs of hyper- or defective mineralization. These changes as consequence of the antiresorptive action of ZOL visible already after 6 months result in beneficial effects on bone matrix mineralization, likely contributing to the significant decrease in fracture incidence observed in these patients 2 years post transplantation.

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Acknowledgments

The authors thank G. Dinst, D. Gabriel, P. Messmer, and S. Thon for careful sample preparation and qBEI measurements and histomorphometric analyses at the bone material laboratory of the Ludwig Boltzmann Institute of Osteology, Vienna, Austria. This study was supported by the AUVA (Austrian Social Insurance for Occupational Risk), the WGKK (Social Health Insurance Vienna), the Austrian Science Fund (FWF P-18325), and the Austrian Academy of Science (OELZELT EST370/04).

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Authors and Affiliations

  1. Ludwig Boltzmann Institute of Osteology at Hanusch Hospital of WGKK and AUVA Trauma Center Meidling, 4th Medical Department at Hanusch Hospital, UKH Meidling, Kundratstr. 37, 1120, Vienna, Austria

    B. M. Misof, P. Roschger & K. Klaushofer

  2. Division of Transplantation, Department of Surgery, Medical University of Vienna, Vienna, Austria

    M. Bodingbauer, T. Wekerle & F. Mühlbacher

  3. Department of Neurosurgery, KA Rudolfstiftung, Vienna, Austria

    B. Pakrah

  4. Department of Internal Medicine III, Division of Nephrology, Medical University of Vienna, Vienna, Austria

    M. Haas, A. Kainz & R. Oberbauer

  5. KH Elisabethinen, Linz, Austria

    A. Kainz & R. Oberbauer

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  1. B. M. Misof
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  2. M. Bodingbauer
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Correspondence to B. M. Misof.

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B. M. Misof and M. Bodingbauer contributed equally.

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Misof, B.M., Bodingbauer, M., Roschger, P. et al. Short-Term Effects of High-Dose Zoledronic Acid Treatment on Bone Mineralization Density Distribution After Orthotopic Liver Transplantation. Calcif Tissue Int 83, 167–175 (2008). https://doi.org/10.1007/s00223-008-9161-2

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