Pregnancy and newborn outcomes after exposure to bisphosphonates: a case-control study

Osteoporos Int. 2019 Jan;30(1):221-229. doi: 10.1007/s00198-018-4672-9. Epub 2018 Aug 31.


We analyzed women and newborn outcome after maternal exposure to BPs. BPs have no teratogenic effect on the 36 analyzed pregnancies compared to unexposed controls matched on women underlying diseases (either systemic disease, either "bone" disease) but some outcome differed: neonatal complications rate in systemic diseases and live birth rate in bone diseases).

Introduction: The effect of bisphosphonates (BPs) during pregnancy remains unclear. We aimed to study pregnancy outcomes in women exposed to BPs during pregnancy.

Methods: Data for cases and controls were from the French Reference Centre of Teratogenic Agents. Cases were women who received BPs in the 6 weeks before or during a pregnancy and had systemic or bone diseases. We included two respectively matched control groups: women with systemic diseases not exposed to BPs and healthy women not exposed to BPs or any teratogenic agent. Four controls were assigned to each case.

Results: Thirty-six women were exposed to BPs including 5 just before pregnancy and 30 during the first trimester; 23 had systemic diseases (systemic lupus erythematosus, n = 5; rheumatoid arthritis, n = 5; other, n = 13) and 13 had bone diseases. Rate of observed congenital malformations did not differ in women with a systemic or a bone disease compared to their respective controls (respectively 2/23 [8.7%] vs 2/92 [2.2%], p = 0.178 and 0/13 [0%] vs 0/52 [0%], p = 1.00). Among women with systemic diseases, non-specific neonatal complications were more frequent for cases (4/16 [25.0%] vs 4/64 [6.3%], p = 0.027). Among women with bone disorders, the live birth rate was lower for cases than healthy controls (8/10 [80%] vs 50/50 [100%], p = 0.025).

Conclusion: We found no major teratogenic effects of BPs, but rates of neonatal complications were increased for women with systemic diseases, as were spontaneous abortions for women with bone diseases likely linked to the severity of the underlying diseases and concomitant medications.

Keywords: Bisphosphonates; Osteoporosis; Pregnancy; Teratogenicity.

MeSH terms

  • Adult
  • Bone Density Conservation Agents / adverse effects*
  • Bone Density Conservation Agents / therapeutic use
  • Case-Control Studies
  • Congenital Abnormalities / etiology
  • Databases, Factual
  • Diphosphonates / adverse effects*
  • Diphosphonates / therapeutic use
  • Female
  • Humans
  • Infant, Newborn
  • Maternal-Fetal Exchange
  • Osteoporosis / drug therapy*
  • Pregnancy
  • Pregnancy Complications / drug therapy*
  • Pregnancy Outcome*
  • Prenatal Exposure Delayed Effects / chemically induced


  • Bone Density Conservation Agents
  • Diphosphonates