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Background <p>Evocalcet is an allosteric modulator of the calcium-sensing receptor (CaSR) that effectively suppresses parathyroid hormone (PTH) secretion in both primary and secondary hyperparathyroidism. However, its effects on the PTH-calcium setpoint and parathyroid cell proliferation remain unclear.</p> Methods <p>We investigated these effects using the PC mouse model of primary hyperparathyroidism, which is characterized by parathyroid-targeted cyclin D1 overexpression . Evocalcet was administered orally at a dose of 0.025 mg/g diet. The PTH-calcium setpoint was evaluated, and the antiproliferative effect of evocalcet on parathyroid cells was assessed using 5-bromo-2′-deoxyuridine (BrdU) incorporation assays. The effects of evocalcet were compared with those of cinacalcet. Expression levels of the vitamin D receptor (VDR) and CaSR in parathyroid glands were also examined.</p> Results <p> Evocalcet significantly reduced the PTH-calcium setpoint in PC mice, restoring it to levels comparable to those observed in wild-type controls. Evocalcet treatment markedly decreased the proportion of BrdU-positive parathyroid cells, indicating suppression of parathyroid cell proliferation. This antiproliferative effect was comparable to that observed with cinacalcet. Neither evocalcet nor cinacalcet altered VDR or CaSR expression in the parathyroid glands.</p> Conclusions <p>Evocalcet, similar to cinacalcet, lowers the PTH-calcium setpoint and inhibits parathyroid cell proliferation in a mouse model of primary hyperparathyroidism. These findings suggest that evocalcet may not only reduce PTH secretion but also attenuate disease progression in hyperparathyroidism.</p>

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Evocalcet improved the PTH–calcium setpoint and suppressed parathyroid proliferation in mice model of primary hyperparathyroidism

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年2月17日

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  • Yasuo Imanishi,
  • Tomoe Hirakawa,
  • Waka Haruyama,
  • Keigo Tsushida,
  • Mariko Sakai,
  • Tetsuya Kitayama,
  • Takehisa Kawata,
  • Emi Donoue,
  • Keisuke Inoue,
  • Ikue Kobayashi,
  • Yuki Nagata,
  • Masafumi Kurajoh,
  • Tetsuo Shoji,
  • Andrew Arnold,
  • Masanori Emoto

摘要

Background

Evocalcet is an allosteric modulator of the calcium-sensing receptor (CaSR) that effectively suppresses parathyroid hormone (PTH) secretion in both primary and secondary hyperparathyroidism. However, its effects on the PTH-calcium setpoint and parathyroid cell proliferation remain unclear.

Methods

We investigated these effects using the PC mouse model of primary hyperparathyroidism, which is characterized by parathyroid-targeted cyclin D1 overexpression . Evocalcet was administered orally at a dose of 0.025 mg/g diet. The PTH-calcium setpoint was evaluated, and the antiproliferative effect of evocalcet on parathyroid cells was assessed using 5-bromo-2′-deoxyuridine (BrdU) incorporation assays. The effects of evocalcet were compared with those of cinacalcet. Expression levels of the vitamin D receptor (VDR) and CaSR in parathyroid glands were also examined.

Results

Evocalcet significantly reduced the PTH-calcium setpoint in PC mice, restoring it to levels comparable to those observed in wild-type controls. Evocalcet treatment markedly decreased the proportion of BrdU-positive parathyroid cells, indicating suppression of parathyroid cell proliferation. This antiproliferative effect was comparable to that observed with cinacalcet. Neither evocalcet nor cinacalcet altered VDR or CaSR expression in the parathyroid glands.

Conclusions

Evocalcet, similar to cinacalcet, lowers the PTH-calcium setpoint and inhibits parathyroid cell proliferation in a mouse model of primary hyperparathyroidism. These findings suggest that evocalcet may not only reduce PTH secretion but also attenuate disease progression in hyperparathyroidism.