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Novel bisphosphonate compound FYB-931 preferentially inhibits aortic calcification in vitamin D3-treated rats

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Abstract

In patients with chronic kidney disease (CKD) or those undergoing hemodialysis, pathological calcific deposition known as ectopic calcification occurs in soft tissue, resulting in a life-threatening disorder. A potent and effective inhibitor of ectopic calcification is eagerly expected. In the current study, the effects of FYB-931, a novel bisphosphonate compound synthesized for the prevention of ectopic calcification, were compared with those of etidronate using both in vitro and in vivo models. In vitro, FYB-931 inhibited calcification of human aortic smooth muscle cells induced by high phosphate medium in a concentration-dependent manner, and the effect was slightly more potent than that of etidronate. In vivo, rats were administered with three subcutaneous injections of vitamin D3 to induce vascular calcification, and were given FYB-931 (1.5, 5, or 10 mg/kg) or etidronate (9, 30, or 60 mg/kg) orally once daily for 14 days. The increased aortic phosphorus content as an index of vascular calcification was inhibited by both FYB-931 and etidronate in a dose-dependent manner; however, FYB-931 was 10 times more potent than etidronate. FYB-931 inhibited serum tartrate-resistant acid phosphatase (TRACP) activity as a bone resorption marker 5.2 times more potently than etidronate. FYB-931, but not etidronate, significantly decreased serum phosphorus levels. The preferential inhibition of aortic calcification by FYB-931 suggested that possible additional effect including a decline in serum phosphorus may lead to an advantage in terms of its efficacy.

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Authors and Affiliations

  1. Research Laboratories 2, Fuji Yakuhin Co., Ltd., 636-1 Iidashinden, Nishi-ku, Saitama, Saitama, 331-0068, Japan

    Koichi Ishida, Naoki Ashizawa, Koji Matsumoto, Seiichi Kobashi, Naoki Kurita & Takashi Iwanaga

  2. Department of Nephrology, Wakayama Medical University, 811-1 Kimiidera, Wakayama, Wakayama, 641-8509, Japan

    Takashi Shigematsu

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  1. Koichi Ishida
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  2. Naoki Ashizawa
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  4. Seiichi Kobashi
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  6. Takashi Shigematsu
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Correspondence to Koichi Ishida.

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Dr. Takashi Shigematsu serves as a consultant for Fuji Yakuhin. The manuscript does not contain clinical studies or patient data.

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Ishida, K., Ashizawa, N., Matsumoto, K. et al. Novel bisphosphonate compound FYB-931 preferentially inhibits aortic calcification in vitamin D3-treated rats. J Bone Miner Metab 37, 796–804 (2019). https://doi.org/10.1007/s00774-019-00987-0

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  • DOI: https://doi.org/10.1007/s00774-019-00987-0

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