Cyclical intravenous pamidronate therapy in children with osteogenesis imperfecta

Abstract

Children affected with osteogenesis imperfecta (OI) have increased morbidity and mortality and no definite treatment has been found yet. Recurrent fractures and bone deformities are the main complications of this disease. Recent studies have shown the ability of intravenous pamidronate to prevent fractures, when given in a cyclical manner [1]. This treatment is being used currently to prevent recurrence of fractures in children with OI but the clinical experience with such therapy is greatly limited. In this brief communication, we report our experience in treating OI children with the intravenous pamidronate during the last 4 years. Total of 28 children with age range of 21 days to 9 years were treated from August 2001 to December 2004. These patients were either direct admissions to paediatric units in Karapitiya Hospital or referred by paediatricians in other hospitals. All patients had suffered at least one fracture in either long bones or ribs before admission. The diagnosis of OI was made clinically by paediatricians in the team, and other metabolic bone diseases such as rickets and renal tubular acidosis were excluded by relevant biochemical tests. Parents were interviewed and benefits and complications of therapy were explained. Children were treated with pamidronate sodium (Aradia by Novartis) 1.5–2.0 mg per kg bodyweight as an infusion in 1/5 isotonic saline over 6-hour period for three consecutive days. This was repeated every 3 months in cyclical manner until either the total bone mineral content (TBMC) became normal (defined as within 2 standard deviations from the mean TBMC of age and sex matched population) or for a maximum of 6 cycles. Children were kept under supervision during therapy for possible sideeffects and open access was given to parents to report any unexpected side-effects. Serum calcium level was done at the end of each treatment session. TBMC was assessed in 18 children by dual energy xray absorptiometry (DXA) using Norland Eclipse XR scanner (Norland Corp, USA). A rapid increase in TBMC was seen in all children, except one, during the period of treatment (Figure 1). All children had either one or more fractures prior to treatment and only two patients suffered fractures after commencing treatment. No major side effects were reported during the therapy. One child had spontaneous rupture of sclera and enucleation due to an accidental trauma while on therapy and he was referred to an ophthalmologist. One child died of pneumonia 2 months after the first cycle. Anaphylactic reaction was noticed in one child and no further pamidronate was given to him. Asymptomatic and mild hypocalcaemia was seen in some children.