Effects of maternal bisphosphonate use on fetal and neonatal outcomes

A review of case reports and other published data on fetal and neonatal outcomes associated with maternal use of bisphosphonate medications is presented.

Bisphosphonates can persist in the bone matrix for years, even after therapy is discontinued, potentially resulting in fetal bisphosphonate exposure during pregnancy. Adverse effects of bisphosphonates on fetal outcomes have been observed in animal studies, but the bisphosphonate doses administered were much higher than those typically used in clinical practice. A literature search of PubMed (1946-May 2014) and ToxNet identified 15 articles describing the use of bisphosphonate medications by women before and/or during pregnancy (in total, the articles described 65 mother-child pairs); the agents used included alendronate, ibandronate, risedronate, etidronate, pamidronate, tiludronate, and zoledronic acid, with the reported durations of use ranging from one-time treatments to periods of months or years. Adverse outcomes possibly attributable to bisphosphonate use included marginal decreases in gestational age and birth weight and transient neonatal electrolyte abnormalities (e.g., hypocalcemia, hypercalcemia, hyperphosphatemia); however, no long-term health consequences were reported in any infant. Overall, the available published data appear to indicate that maternal bisphosphonate use does not pose a high risk of fetal or neonatal harm. Nonetheless, in cases of known or suspected fetal bisphosphonate exposure, monitoring for neonatal hypocalcemia and associated neuromuscular and cardiac symptoms is advised.

A limited body of published data suggests that maternal use of bisphosphonates before or during pregnancy does not have serious fetal or neonatal adverse effects.