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The Effects of Bone Remodeling Inhibition by Alendronate on Three-Dimensional Microarchitecture of Subchondral Bone Tissues in Guinea Pig Primary Osteoarthrosis

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Abstract

We assessed whether increase of subchondral bone density enhances cartilage stress during impact loading, leading to progressive cartilage degeneration and accelerated osteoarthrosis (OA) progression. Sixty-six male guinea pigs were randomly divided into six groups. During a 9-week treatment period, four groups received twice-weekly subcutaneous injections of alendronate (ALN) in two doses: two groups received 10 μg/kg and two groups received 50 μg/kg. The two control groups received vehicle. After 9 weeks, one 10 μg/kg ALN group, one 50 μg/kg ALN group, and one control group were killed. The remaining three groups (17-week groups) were left for an additional 8 weeks, receiving the same treatment regimen before death. The left proximal tibiae were scanned by micro-computed tomography to quantify the microarchitecture of subchondral bone, followed by mechanical testing and determination of collagen and mineral. The control groups had typical OA-related cartilage degeneration at 9 and 17 weeks, whereas the 50 μg/kg ALN group had even worse degeneration in the medial condyle. It is unclear whether there is a direct or a secondary effect of ALN on the cartilage. The 9-week ALN group had significantly greater subchondral plate thickness. The 9- and 17-week groups had similar changes of cancellous bone microarchitecture, with greater volume fraction and connectivity and an extremely plate-like structure. The 9-week ALN group had greater bone mineral concentration, and the 17-week ALN group had reduced collagen concentration and greater mineral concentration. Treatment with ALN did not significantly change the mechanical properties of the cancellous bone.

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Acknowledgment

This study was supported by the Danish Rheumatism Association (Gigtforeningen, grant 233-949-11.07.00), Hørslev-fonden, and Helga og Peter Kornings Fond. We thank Jane Pauli, Anette Milton, and Eva K. Mikkelsen for skillful technical assistance and Ulla Dansberg and Hilmar Hald for animal care.

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Authors and Affiliations

  1. Orthopedic Research Laboratory, Department of Orthopedics, Aarhus University Hospital, Aarhus, Denmark

    Ming Ding & Ivan Hvid

  2. Orthopedic Research Laboratory, Department of Orthopedics, Odense University Hospital, Winsløwparken 15, 3.sal 8, DK-500, Odense C, Denmark

    Ming Ding

  3. Department of Connective Tissue Biology, Institute of Anatomy, University of Aarhus, Aarhus, Denmark

    Carl Christian Danielsen

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  1. Ming Ding
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  2. Carl Christian Danielsen
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  3. Ivan Hvid
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Correspondence to Ming Ding.

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Ding, M., Danielsen, C.C. & Hvid, I. The Effects of Bone Remodeling Inhibition by Alendronate on Three-Dimensional Microarchitecture of Subchondral Bone Tissues in Guinea Pig Primary Osteoarthrosis. Calcif Tissue Int 82, 77–86 (2008). https://doi.org/10.1007/s00223-007-9093-2

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  • DOI: https://doi.org/10.1007/s00223-007-9093-2

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