Abstract
The goal of the study was to compare the effects of minodronic acid on bone mineral density (BMD) and bone turnover in a rat ovariectomized (OVX) osteoporosis model, using two intermittent treatment regimens (weekly and 4 continuous days every 4 weeks) and a daily regimen. Female F344 rats (age 14 weeks) underwent ovariectomy or a sham operation. Minodronic acid was orally administered at 0.042, 0.21, and 1.05 mg/kg in the intermittent regimens, and at 0.03 and 0.15 mg/kg in the daily regimen for 12 weeks from the day after surgery. Minodronic acid dose-dependently ameliorated the decreases in areal BMD of the lumbar vertebrae and femur, and volumetric BMD of total and trabecular bone in the distal femur. Minodronic acid also suppressed the increase in urinary deoxypyridinoline levels and reduced serum osteocalcin levels. In bone histomorphometry, all three minodronic acid regimens suppressed OVX-induced increases in bone turnover at the tissue level and ameliorated all structural indices, except that an effect on trabecular thickness only occurred with daily treatment. In conclusion, minodronic acid administered weekly or for 4 continuous days every 4 weeks suppressed increased bone resorption and BMD to a similar extent to that of a similar total dose given daily in a rat OVX model.
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Acknowledgments
We thank H. Tsusaki (Shin Nippon Biomedical Laboratories, Ltd.) for their expertise and technical support in animal care and a BMD assessments, and staff of SkeleTech Inc. for performing histomorphometric analysis.
Human and Animal Rights and Informed Consent
This study was ethically approved by the Institutional Animal Care and Use Committee of Shin Nippon Biomedical Laboratories, Ltd. (Kagoshima, Japan) and performed in accordance with the criteria defined by the rules of the committee.
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All authors are research scientists at Ono Pharmaceutical Co., Ltd. Minodronic acid was launched by Ono Pharmaceutical Co., Ltd. and Astellas Pharma Inc. in Japan. MT and HM are applicants for use patent of intermittent regimen.
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Tanaka, M., Mori, H., Kayasuga, R. et al. Effect of Intermittent and Daily Regimens of Minodronic Acid on Bone Metabolism in an Ovariectomized Rat Model of Osteoporosis. Calcif Tissue Int 95, 166–173 (2014). https://doi.org/10.1007/s00223-014-9876-1
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DOI: https://doi.org/10.1007/s00223-014-9876-1