J Pediatr Genet 2020; 09(02): 093-100
DOI: 10.1055/s-0039-1700972
Original Article
Georg Thieme Verlag KG Stuttgart · New York

Hypocalcemia following Neridronate Administration in Pediatric Patients with Osteogenesis Imperfecta: A Prospective Observational Study

Evelina Maines
1   Pediatric Unit, Department of Women's and Children's Health, Provincial Centre for Rare Diseases, Azienda Provinciale per i Servizi Sanitari della Provincia Autonoma di Trento, Trento, Italy
Elisa Tadiotto
2   Pediatric Division, Department of Surgical Sciences, Dentistry, Gynecology and Pediatrics, University of Verona, Verona, Italy
Grazia Morandi
3   Neonatal Intensive Care Unit, Department of Pediatrics, “C. Poma” Hospital, Mantova, Italy
Michela Fedrizzi
4   Pediatric Unit, Pediatric Cardiology Service, Department of Women's and Children's Health, Azienda Provinciale per i Servizi Sanitari della Provincia Autonoma di Trento, Trento, Italy
Rossella Gaudino
2   Pediatric Division, Department of Surgical Sciences, Dentistry, Gynecology and Pediatrics, University of Verona, Verona, Italy
Paolo Cavarzere
2   Pediatric Division, Department of Surgical Sciences, Dentistry, Gynecology and Pediatrics, University of Verona, Verona, Italy
Alessandra Guzzo
5   Laboratory Unit, Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Verona, Italy
Franco Antoniazzi
6   Department of Surgical Sciences, Dentistry, Gynecology and Pediatrics, Regional Center for the Diagnosis and Treatment of Children and Adolescents with Rare Skeletal Disorders, Pediatric Clinic, University of Verona, Verona, Italy
› Author Affiliations
Funding None.
Further Information

Publication History

28 September 2019

25 November 2019

Publication Date:
06 January 2020 (online)


The use of intravenous bisphosphonates has been linked to hypocalcemia both in children and adults with osteogenesis imperfecta (OI). The aims of this study were: (1) to investigate the incidence of hypocalcemia in the first 48 hours (T48) after neridronate infusion in a pediatric population with OI and (2) to assess any correlation between the baseline values of calcium, vitamin D (25-hydroxyvitamin D) and bone turnover markers, and the postinfusion calcium values. We conducted a prospective observational study on 37 pediatric patients. All patients were treated with a single infusion of neridronate at a dose of 1 to 2 mg/kg. The study provided two postinfusion reassessments: 24 hours (T24) and T48 after neridronate administration. Hypocalcemia was observed in 11% of patients at T24 and in 50% of patients at T48 from neridronate infusion. We observed a positive linear correlation between the baseline vitamin D values and postinfusion calcium values, both at baseline and at T24 and T48. Hypocalcemia was mild and asymptomatic in all cases. Postinfusion calcium levels were related to baseline vitamin D levels. Consequently, low vitamin D levels should be considered a significant risk factor for hypocalcemia and should be carefully investigated and treated before neridronate infusion.

Authors' Contributions

E.M. conceived the work and wrote the draft; E.T. and G.T. revised the manuscript and prepared figures and tables; M.F. did ECG interpretation and revised the draft; A.G. performed laboratory analysis; R.G. and P.C. ensured the accuracy of the data and revised the manuscript critically for important intellectual content. The authors acknowledge that they participated sufficiently in the work to take public responsibility for its content. All the authors approve the submitted version of the manuscript.

Compliance with Ethical Standards

The latest revision of the Helsinki declaration as well as the Oviedo declaration was the basis for the ethical conduct of the study. The study protocol was designed and conducted to ensure adherence to the principles and procedures of good clinical practice and to comply with the Italian laws.

The study was approved by the ethics committee for clinical trials of the Provinces of Verona and Rovigo (72CESC/HBPOI). All patients and/or their parents signed an informed consent.

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