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Effect of Combined Teriparatide and Monthly Risedronate Therapy on Cancellous Bone Mass in Orchidectomized Rats: A Bone Histomorphometry Study

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Abstract

This study investigated the effects of combined teriparatide (an anabolic agent) and monthly risedronate (an anti-resorptive agent) therapy on cancellous bone mass in orchidectomized (ORX) rats. Fifty 14-week-old male Sprague–Dawley rats were randomized into five groups of ten animals each: sham-operation + vehicle; ORX + vehicle; ORX + risedronate (90 μg/kg subcutaneous, every 4 weeks); ORX + teriparatide (30 μg/kg subcutaneous, three times per week); and ORX + risedronate + teriparatide. After the 12-week experimental period, cancellous bone in the tibial proximal metaphysis was examined by static and dynamic histomorphometric analyses. ORX decreased bone volume per total volume (BV/TV) and trabecular number (Tb.N), and increased trabecular separation (Tb.Sp). Risedronate increased BV/TV and Tb.N above the sham control values, while teriparatide prevented the ORX-induced decrease in BV/TV and increased trabecular width (Tb.Wi) above sham control levels. Risedronate decreased Tb.Sp below control values, while teriparatide prevented the ORX-induced increase in Tb.Sp. The combination of teriparatide and risedronate further increased BV/TV and Tb.N and decreased Tb.Sp as a result of suppression of bone remodeling, compared with teriparatide alone. These results suggest that teriparatide and monthly risedronate exert different effects on cancellous bone structure and thus have additive effects on cancellous bone mass in ORX rats.

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Acknowledgments

This research was supported by Asahi Kasei Pharma, Co. Ltd., Tokyo, Japan.

Conflict of interest

J. Iwamoto and A. Seki declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

This experiment was performed at the laboratory of Hamri Co., Ltd. (Ibaraki, Japan), which was approved by the Association for the Assessment and Accreditation of Laboratory Animal Care (AAALAC) International. All procedures performed in the experiment involving animals were in accordance with the ethical standards of the institution or practice at Hamri Co., Ltd. (Ibaraki, Japan). The experimental protocol was approved by the Institutional Animal Care and Use Committee (IACUC) of Hamri Co., Ltd. (Ibaraki, Japan).

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Authors and Affiliations

  1. Institute for Integrated Sports Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan

    Jun Iwamoto

  2. Hamri Co., Ltd., Koga, Ibaraki, Japan

    Azusa Seki

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  1. Jun Iwamoto
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  2. Azusa Seki
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Correspondence to Jun Iwamoto.

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Iwamoto, J., Seki, A. Effect of Combined Teriparatide and Monthly Risedronate Therapy on Cancellous Bone Mass in Orchidectomized Rats: A Bone Histomorphometry Study. Calcif Tissue Int 97, 23–31 (2015). https://doi.org/10.1007/s00223-015-0006-5

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  • DOI: https://doi.org/10.1007/s00223-015-0006-5

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