Neonatal transient hypophosphatemic hypercalciuric rickets in dizygous twins: A role for maternal alendronate therapy before pregnancy or antireflux medications?

Background: Bisphosphonates (BP) are sometimes used in children and young women, but their use requires expertise and caution due to the relative lack of long-term efficacy and safety data.

Clinical Cases: We report on two dizygotic male twins with a past of mild prematurity who presented at the age of 2 months with moderate clinical craniotabes, hypophosphatemia, normal circulating calcium, severe hypercalciuria, and low parathyroid hormone levels. Following supplementation with oral phosphorus and native vitamin D, the clinical and biological abnormalities disappeared within 2 months. Since the twins were dizygotic and were identical in terms of clinical presentation and progression, the only likely explanation for these transient mineral abnormalities was prenatal or neonatal exposure to a toxic agent. Taking into account their medical past, two drugs were possibly involved: either oral alendronate that their mother had received before pregnancy for misdiagnosed osteoporosis or antireflux medications, or both.

Discussion: We believe that these two cases could correspond to the first description of a potential mother-to-fetus transmission of alendronate, inducing early and transient hypophosphatemic rickets, the clinical picture being worsened by the antireflux drugs impairing intestinal phosphate absorption. For pediatric rheumatologists, this raises the question of more clearly defining the indications for BP in female children and teenagers; for rheumatologists, this also demonstrates the importance of correctly diagnosing osteoporosis and not using BP off-label, especially in women of child-bearing age.