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

Evelina Maines; Elisa Tadiotto; Grazia Morandi; Michela Fedrizzi; Rossella Gaudino; Paolo Cavarzere; Alessandra Guzzo; Franco Antoniazzi

doi:10.1055/s-0039-1700972

Journal of Pediatric Genetics, Inhaltsverzeichnis

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

¹Pediatric 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

²Pediatric Division, Department of Surgical Sciences, Dentistry, Gynecology and Pediatrics, University of Verona, Verona, Italy

,

Grazia Morandi

³Neonatal Intensive Care Unit, Department of Pediatrics, “C. Poma” Hospital, Mantova, Italy

,

Michela Fedrizzi

⁴Pediatric 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

²Pediatric Division, Department of Surgical Sciences, Dentistry, Gynecology and Pediatrics, University of Verona, Verona, Italy

,

Paolo Cavarzere

²Pediatric Division, Department of Surgical Sciences, Dentistry, Gynecology and Pediatrics, University of Verona, Verona, Italy

,

Alessandra Guzzo

⁵Laboratory Unit, Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Verona, Italy

,

Franco Antoniazzi

⁶Department 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

› Institutsangaben

Abstract

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.

Keywords

neridronate - hypocalcemia - osteogenesis imperfecta - children - vitamin D deficiency

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Referenzen

References
1 Rauch F, Glorieux FH. Osteogenesis imperfecta. Lancet 2004; 363 (9418): 1377-1385
2 Antoniazzi F, Mottes M, Fraschini P, Brunelli PC, Tatò L. Osteogenesis imperfecta: practical treatment guidelines. Paediatr Drugs 2000; 2 (06) 465-488
3 Tournis S, Dede AD. Osteogenesis imperfecta - a clinical update. Metabolism 2018; 80: 27-37
4 Kang H, Aryal A C S, Marini JC. Osteogenesis imperfecta: new genes reveal novel mechanisms in bone dysplasia. Transl Res 2017; 181: 27-48
5 Marini JC, Forlino A, Bächinger HP. , et al. Osteogenesis imperfecta. Nat Rev Dis Primers 2017; 3: 17052
6 Brunetti G, Papadia F, Tummolo A. , et al. Impaired bone remodeling in children with osteogenesis imperfecta treated and untreated with bisphosphonates: the role of DKK1, RANKL, and TNF-α. Osteoporos Int 2016; 27 (07) 2355-2365
7 Sillence DO, Senn A, Danks DM. Genetic heterogeneity in osteogenesis imperfecta. J Med Genet 1979; 16 (02) 101-116
8 Bonafe L, Cormier-Daire V, Hall C. , et al. Nosology and classification of genetic skeletal disorders: 2015 revision. Am J Med Genet A 2015; 167A (12) 2869-2892
9 Monti E, Mottes M, Fraschini P. , et al. Current and emerging treatments for the management of osteogenesis imperfecta. Ther Clin Risk Manag 2010; 6: 367-381
10 Marom R, Lee YC, Grafe I, Lee B. Pharmacological and biological therapeutic strategies for osteogenesis imperfecta. Am J Med Genet C Semin Med Genet 2016; 172 (04) 367-383
11 Cheung MS, Glorieux FH. Osteogenesis Imperfecta: update on presentation and management. Rev Endocr Metab Disord 2008; 9 (02) 153-160
12 Marr C, Seasman A, Bishop N. Managing the patient with osteogenesis imperfecta: a multidisciplinary approach. J Multidiscip Healthc 2017; 10: 145-155
13 Biggin A, Munns CF. Long-term bisphosphonate therapy in osteogenesis Imperfecta. Curr Osteoporos Rep 2017; 15 (05) 412-418
14 Fernández D, Ramis R, Ortega-Castro J, Casasnovas R, Vilanova B, Frau J. New insights into human farnesyl pyrophosphate synthase inhibition by second-generation bisphosphonate drugs. J Comput Aided Mol Des 2017; 31 (07) 675-688
15 Papapetrou PD. Bisphosphonate-associated adverse events. Hormones (Athens) 2009; 8 (02) 96-110
16 Baroncelli GI, Bertelloni S. The use of bisphosphonates in pediatrics. Horm Res Paediatr 2014; 82 (05) 290-302
17 Kreutle V, Blum C, Meier C. , et al. Bisphosphonate induced hypocalcaemia - report of six cases and review of the literature. Swiss Med Wkly 2014; 144: w13979
18 Wagner S, Poirot I, Vuillerot C, Berard C. Tolerance and effectiveness on pain control of Pamidronate® intravenous infusions in children with neuromuscular disorders. Ann Phys Rehabil Med 2011; 54 (06) 348-358
19 Rush ET, DeHaai K, Kreikemeier RM, Lutz RE. Evaluation and comparison of safety, convenience and cost of administering intravenous pamidronate infusions to children in the home and ambulatory care settings. J Pediatr Endocrinol Metab 2012; 25 (5-6): 493-497
20 Rothenbuhler A, Marchand I, Bougnères P, Linglart A. Risk of corrected QT interval prolongation after pamidronate infusion in children. J Clin Endocrinol Metab 2010; 95 (08) 3768-3770
21 Chilbule SK, Madhuri V. Complications of pamidronate therapy in paediatric osteoporosis. J Child Orthop 2012; 6 (01) 37-43
22 Forin V, Arabi A, Guigonis V, Filipe G, Bensman A, Roux C. Benefits of pamidronate in children with osteogenesis imperfecta: an open prospective study. Joint Bone Spine 2005; 72 (04) 313-318
23 Zeitlin L, Rauch F, Travers R, Munns C, Glorieux FH. The effect of cyclical intravenous pamidronate in children and adolescents with osteogenesis imperfecta type V. Bone 2006; 38 (01) 13-20
24 Jakubowska-Pietkiewicz E, Chlebna-Sokół D. New trends in the treatment of osteogenesis imperfecta type III - own experience. Ortop Traumatol Rehabil 2008; 10 (06) 593-601
25 Lin CH, Chien YH, Peng SF. , et al. Cyclic pamidronate infusion for neonatal-onset osteogenesis imperfecta. Pediatr Neonatol 2014; 55 (04) 306-311
26 Gatti D, Antoniazzi F, Prizzi R. , et al. Intravenous neridronate in children with osteogenesis imperfecta: a randomized controlled study. J Bone Miner Res 2005; 20 (05) 758-763
27 Nasomyont N, Hornung LN, Gordon CM, Wasserman H. Outcomes following intravenous bisphosphonate infusion in pediatric patients: a 7-year retrospective chart review. Bone 2019; 121: 60-67
28 George S, Weber DR, Kaplan P, Hummel K, Monk HM, Levine MA. Short-term safety of zoledronic acid in young patients with bone disorders: an extensive institutional experience. J Clin Endocrinol Metab 2015; 100 (11) 4163-4171
29 Vuorimies I, Toiviainen-Salo S, Hero M, Mäkitie O. Zoledronic acid treatment in children with osteogenesis imperfecta. Horm Res Paediatr 2011; 75 (05) 346-353
30 Liamis G, Milionis HJ, Elisaf M. A review of drug-induced hypocalcemia. J Bone Miner Metab 2009; 27 (06) 635-642
31 Saggese G, Vierucci F, Prodam F. , et al. Vitamin D in pediatric age: consensus of the Italian Pediatric Society and the Italian Society of Preventive and Social Pediatrics, jointly with the Italian Federation of Pediatricians. Ital J Pediatr 2018; 44 (01) 51
32 Nicholson JF, Pesce MA. In: Behrman RE, Kliegman RM, Arvin AM, Nelson WE. , eds. Textbook of Pediatrics. Philadelphia: WB Saunders Co.; 1995: 2037
33 Szulc P, Seeman E, Delmas PD. Biochemical measurements of bone turnover in children and adolescents. Osteoporos Int 2000; 11 (04) 281-294
34 Rauchenzauner M, Schmid A, Heinz-Erian P. , et al. Sex- and age-specific reference curves for serum markers of bone turnover in healthy children from 2 months to 18 years. J Clin Endocrinol Metab 2007; 92 (02) 443-449
35 Yang L, Grey V. Pediatric reference intervals for bone markers. Clin Biochem 2006; 39 (06) 561-568
36 Rautaharju PM, Surawicz B, Gettes LS. , et al; American Heart Association Electrocardiography and Arrhythmias Committee, Council on Clinical Cardiology; American College of Cardiology Foundation; Heart Rhythm Society; Endorsed by the International Society for Computerized Electrocardiology. AHA/ACCF/HRS recommendations for the standardization and interpretation of the electrocardiogram: part IV: the ST segment, T and U waves, and the QT interval: a scientific statement from the American Heart Association Electrocardiography and Arrhythmias Committee, Council on Clinical Cardiology; the American College of Cardiology Foundation; and the Heart Rhythm Society. J Am Coll Cardiol 2009; 53 (11) 982-991
37 Johnson JN, Ackerman MJ. QTc: how long is too long?. Br J Sports Med 2009; 43 (09) 657-662
38 Heemskerk CPM, Pereboom M, van Stralen K. , et al. Risk factors for QTc interval prolongation. Eur J Clin Pharmacol 2018; 74 (02) 183-191
39 Gupta A, Lawrence AT, Krishnan K, Kavinsky CJ, Trohman RG. Current concepts in the mechanisms and management of drug-induced QT prolongation and torsade de pointes. Am Heart J 2007; 153 (06) 891-899
40 Roden DM. Drug-induced prolongation of the QT interval. N Engl J Med 2004; 350 (10) 1013-1022
41 Viskin S, Justo D, Halkin A, Zeltser D. Long QT syndrome caused by noncardiac drugs. Prog Cardiovasc Dis 2003; 45 (05) 415-427
42 Holick MF, Binkley NC, Bischoff-Ferrari HA. , et al; Endocrine Society. Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 2011; 96 (07) 1911-1930
43 Society for Adolescent Health and Medicine. Recommended vitamin D intake and management of low vitamin D status in adolescents: a position statement of the society for adolescent health and medicine. J Adolesc Health 2013; 52 (06) 801-803
44 Burkhart P, Dunbar-Jacob J. Adherence research in the pediatric and adolescent populations: a decade in review. In: Hayman L, Mahom M, Turner R. , eds. Chronic Illness in children: An Evidence-Based Approach. New York: Springer; 2002: 199-229
45 De Geest S, Sabaté E. Adherence to long-term therapies: evidence for action. Eur J Cardiovasc Nurs 2003; 2 (04) 323
46 Gutteridge DH, Retallack RW, Ward LC. , et al. Clinical, biochemical, hematologic, and radiographic responses in Paget's disease following intravenous pamidronate disodium: a 2-year study. Bone 1996; 19 (04) 387-394
47 Polyzos SA, Anastasilakis AD, Terpos E. Transient secondary hyperparathyroidism following intravenous infusion of zoledronic acid. Support Care Cancer 2009; 17 (10) 1329-1330
48 Rauch F, Plotkin H, Travers R, Zeitlin L, Glorieux FH. Osteogenesis imperfecta types I, III, and IV: effect of pamidronate therapy on bone and mineral metabolism. J Clin Endocrinol Metab 2003; 88 (03) 986-992
49 Cremers SC, Eekhoff ME, Den Hartigh J, Hamdy NA, Vermeij P, Papapoulos SE. Relationships between pharmacokinetics and rate of bone turnover after intravenous bisphosphonate (olpadronate) in patients with Paget's disease of bone. J Bone Miner Res 2003; 18 (05) 868-875