Bisphosphonate Therapy in Pregnancy

Presentation Number: SAT 334
Date of Presentation: April 1st, 2017

Matthew Nicholson* and Rene J Harper
Augusta University, Augusta, GA

Abstract

Objective:

To discuss the use of bisphosphonate use during pregnancy and review the effects on neonatal outcomes

Case presentation:

A 30 year old female at 26 weeks gestation presented to a community hospital with hypercalcemia, altered mental status, and preterm labor. She had been diagnosed with invasive ductal breast carcinoma four months earlier. Hypercalcemia did not respond to IV fluids and nasal calcitonin and she was transferred to our institution. Evaluation showed serum calcium 20.1 mg/dL (8.7 - 10.4), ionized calcium 11.1 mg/dL (4.5 - 5.3), albumin 3.3 g/dL (3.2-4.0), magnesium 2.2 mg/dL (1.3 - 2.7), intact PTH undetectable, total 25-(OH) vitamin D 10.6 ng/mL (30 – 100), 1,25-(OH)2 vitamin D 72 pg/mL (18 – 78), and PTHrP 9.5 pmol/L (< 2.0). She was continued on IV fluids and started on calcitonin 4 units/kg SC every 12 hours. Due to continued severe hypercalcemia pamidronate 90 mg was given intravenously. She required hemodialysis for 3 days while waiting for bisphosphonate therapy to work, after which her serum calcium declined to 8.3 mg/dL. At this time her uterine contractions improved and preterm labor ceased. Labor was induced due to concern for further deterioration in her clinical condition and prolonged fetal risk. Her newborn had transient hypocalcemia but an otherwise uneventful stay in the NICU.

Discussion:

This is one of a limited number of reported cases of IV pamidronate given for hypercalcemia during pregnancy. Bisphosphonates are considered to be contraindicated in pregnancy, as animal studies have shown bisphosphonates cross the placenta and may lead to preterm labor and harm to the mother and fetus. Studies of bisphosphate administration in rodents have reported dystocia and abnormal tooth growth, tremors and hypocalcemia-associated death in the pups. In human newborns whose mother received IV pamidronate, transient, mild hypocalcemia has been reported, which resolved after 5-10 days as in our patient’s newborn. Neonatal hypocalcemia may be secondary to fetal parathyroid hormone suppression from maternal hypercalcemia and/or from the direct effects of bisphosphonates. In previous cases, growth and development of the newborn have been reported normal at 8 weeks and at 10 months. Despite the risks to the fetus, IV bisphosphonates produce a reduction of the serum calcium that reduces uterine contractions, thus leading to more stable fetal monitoring until delivery. Aggressive hydration and calcitonin are only temporary measures in hypercalcemia during pregnancy, and the risks versus benefits of IV bisphosphonates need to be considered. Hemodialysis may be required when medical therapy fails to resolve the hypercalcemia in a timely manner. This case demonstrates the short-term safety and efficacy of IV pamidronate for humoral hypercalcemia of malignancy during pregnancy. The long-term effects on growth and skeletal development of the infant are not known.

 

Nothing to Disclose: MN, RJH