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Reproductive toxicity of denosumab in cynomolgus monkeys

Jeanine L Bussiere1, Ian Pyrah, Rogely Boyce

  • 1Amgen Inc., One Amgen Center Dr., Thousand Oaks, CA 91320, United States.

Reproductive Toxicology (Elmsford, N.Y.)
|July 27, 2013
PubMed

Insights

Denosumab did not harm fetuses, but it increased stillbirths and infant mortality in monkeys. Effects on infant growth and development were observed, with most bone changes recovering by six months.

Area of Science:

  • Reproductive toxicology
  • Pharmacology
  • Skeletal biology

Background:

  • Denosumab is a monoclonal antibody inhibiting bone resorption by targeting RANKL.
  • RANKL is crucial for osteoclast development and function.

Purpose of the Study:

  • To assess the reproductive toxicity of denosumab in reproductive animal models.
  • To evaluate denosumab's effects on embryofetal development and pre- and postnatal outcomes.

Main Methods:

  • Reproductive toxicity was evaluated in cynomolgus monkeys through embryofetal development and pre-postnatal toxicity studies.
  • Dosing occurred between gestational day 20 and parturition.

Main Results:

  • Denosumab did not cause maternal toxicity, fetal harm, or teratogenicity in the embryofetal study.
  • The pre-postnatal study showed increased stillbirths and one maternal death.
  • Infants exposed in utero experienced increased postnatal mortality, reduced weight gain, and developmental issues, primarily affecting bones and lymph nodes.

Conclusions:

  • Denosumab's reproductive toxicity findings in monkeys are consistent with its pharmacological action.
  • While most bone effects in infants resolved by 6 months, postnatal mortality and developmental impacts were noted.
Keywords:
Cynomolgus monkeysDenosumabEmbryofetal toxicityPre-postnatal toxicityReproductive toxicity

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