Bone Abstracts

Background: A 3.2 year old boy was reviewed following 2 low trauma femoral fractures. He had been born at 31 weeks gestation, his mother having been diagnosed with metastatic breast cancer at 12 weeks gestation. She received chemotherapy at 20 weeks gestation and was given intravenous zoledronic acid (ZA) during the second trimester for hypercalcaemia.

Presenting problem: At 2.7 years, he fell on a tarmacked surface sustaining a diaphyseal fracture of his right femur which was managed with a hip spica. At 3.2 years, he sustained a fracture of his left femur when he fell from standing onto a cushion. Bone biochemistry was normal (apart from a 25OH vitamin D 48 nmol/L - subsequently treated).

Clinical Management: Examination revealed blue sclerae and hypermobile joints. Dentition was normal. There was no family history of bone disease. A clinical diagnosis of type 1 osteogenesis imperfecta was made. DXA was unremarkable (L2-4 BMD 0.588 g/cm²; Z score −0.4). A lateral spine radiograph was undertaken to exclude vertebral loss of height/fractures. Whilst no fractures were found there was a strikingly unusual radiographic appearance; there was a well-defined rectangular area of hyperdensity in the centre of each vertebra, with lower density bone around it. The appearance was suggestive of a retained calcified scaffold of each vertebra from an earlier point in growth. The view of the clinicians and radiologist was that the cause of this ‘bone-in-bone’ appearance was consistent with and likely to be due to the ZA administered to the child’s mother during the second trimester of pregnancy. Joint review with a clinical geneticist resulted in agreement that the clinical diagnosis was sufficiently clear to render COL1A1/COL1A2 screening unnecessary.

Discussion: Adverse effects of bisphosphonates on the fetal skeleton have been observed in animal studies, although often with doses much higher than those used in clinical practice. However no long-term health consequences have been reported in any infant. In this case study we report persisting skeletal abnormalities in the fetus caused by exposure to bisphosphonates during pregnancy. Further studies are needed to confirm the safety of bisphosphonate use during pregnancy on the fetus and the neonate.

Disclosure: Nick Bishop: Consults for Alexion, Mereo, UCB and Amgen, and receives grant support for clinical studies from Alexion and Amgen. Paul Arundel: Research grant/honoraria/ expenses - Alexion and Kyowa Kirin. Expenses - BioMarin Amaka C. Offiah: Research grant/honoraria/ expenses – Alexion. Honoraria/Expenses - BioMarin