Pregnancy outcome following in utero exposure to bisphosphonates

Bone. 2009 Mar;44(3):428-30. doi: 10.1016/j.bone.2008.11.001. Epub 2008 Nov 14.


Background and aim: The safety of bisphosphonates in human pregnancy has not been well established. To characterize pregnancy outcome in women receiving bisphosphonates, we conducted a multi-centre, prospective cohort study with a comparison group.

Methods: Patients were recruited through 3 teratogen information centres in Canada and South Korea. We followed 21 women exposed to bisphosphonates during or <3 months before pregnancy, and 21 matched-comparison group women without exposure to known teratogens. Pregnancy/neonatal outcome data were collected by interview. The primary endpoint was neonatal outcome including major birth defects. The secondary endpoints included other pregnancy outcomes such as spontaneous abortions.

Results: Indication of the therapy was osteoporosis in all patients. There was no difference in the maternal demographics between the 2 groups. In the bisphosphonate group, there were 18 live births, 2 spontaneous abortions and 1 therapeutic abortion, which were not significantly different from the comparison group. The mean gestational age (mean+/-SD) of the bisphosphonate group was 38.7+/-1.9 weeks (comparison group: 39.3+/-1.9 weeks; P=0.42), and the mean birth weight was 3.1+/-0.3 kg (comparison group: 3.3+/-0.5 kg; P=0.11). In the bisphosphonate group, there was a child diagnosed with Apert syndrome, an autosomal dominant acrocephalosyndactyly, with a fibroblast growth factor 2 mutation.

Conclusion: Coupled with existing data in the literature, our findings suggest that preconceptional and first-trimester use of bisphosphonates may not pose substantial fetal risks.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abnormalities, Drug-Induced
  • Adult
  • Bone Density Conservation Agents / adverse effects
  • Bone Density Conservation Agents / therapeutic use*
  • Diphosphonates / adverse effects
  • Diphosphonates / therapeutic use*
  • Female
  • Fetus / drug effects
  • Gestational Age
  • Humans
  • Osteoporosis / drug therapy*
  • Pregnancy
  • Pregnancy Outcome*
  • Pregnancy Trimester, First
  • Prenatal Exposure Delayed Effects
  • Prospective Studies


  • Bone Density Conservation Agents
  • Diphosphonates