ESPE Abstracts

Background: Bisphosphonates act to increase bone mass by inhibition of osteoclastic bone resorption and reduction of bone turnover. Since the successful use of bisphosphonates in children with osteogenesis imperfecta, a broad range of pediatric indications with variable underlying pathomechanism emerged. While the use of bisphosphonates appears to be safe in children, data on risk factors for acute-phase reaction are sparse. A systematic characterization of side effects associated with factors including baseline musculoskeletal pain, mobility and wellbeing has not been performed in pediatric patients to our knowledge.

Materials and Methods: Pediatric patients with commencement of a bisphosphonate treatment have been recruited in 10 centers in the UK, Germany and Austria. A standardized questionnaire including pain, wellbeing, and mobility scoring was completed before therapy onset. Acute-phase effects as reported by the patient / caregiver have been retrieved by a telephone call after the infusion. Data was evaluated by multivariate analysis and linear regression models with correction for age and sex.

Results: 139 children and adolescents (Mean 9.8y, 39% females, 36% Osteogenesis imperfecta) with newly commenced bisphosphonate therapy were included. The majority of patients had a history of fractures (64% vertebral, 48% non-vertebral). Zoledronate was used in 83% of cases. The majority of patients (75%) received antipyretics, cholecalciferol and/or calcium supplements as prophylactic treatment. Febrile episodes have been reported by 45% of patients after the infusion with an average duration of 2.5d. Nausea was noted in 24% of patients with a mean duration of 2.9d. Patients with inflammatory conditions (e.g. CRMO) revealed higher rates (P=0.045) and longer duration of fever (P=0.044). Prophylactic treatment did neither alter the rate nor the duration of febrile episodes and nausea. Patients with more pain experienced higher rates of febrile episodes (P<0.05) with longer duration (P<0.01). Vitamin D status or baseline calcium did not alter side-effect frequencies.

Discussion: Acute-phase reactions affect a substantial percentage of pediatric patients with newly commences bisphosphonate treatment. While prophylactic treatment was not associated with lower side effect rates, risk populations including patients with inflammatory disorders or patients with high baseline pain scores might benefit from intensified pain management or modification of the initial bisphosphonate dosage. Knowledge on the risk factors helps to prevent treatment-associated adverse effects and improve acceptance of bisphosphonate use in pediatric bone diseases. This research was supported by the ESPE Research Unit Grant