Zoledronate for Osteogenesis imperfecta: evaluation of safety profile in children

Chanchal Kumar; Inusha Panigrahi; Abhishek Somasekhara Aradhya; Babu Lal Meena; Niranjan Khandelwal

doi:10.1515/jpem-2015-0351

Article

Zoledronate for Osteogenesis imperfecta: evaluation of safety profile in children

Chanchal Kumar , Inusha Panigrahi , Abhishek Somasekhara Aradhya , Babu Lal Meena and Niranjan Khandelwal

Published/Copyright: May 28, 2016

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From the journal Journal of Pediatric Endocrinology and Metabolism Volume 29 Issue 8

Abstract

Background:

The advent of bisphosphonates (BPs) has revolutionised the outcome of Osteogenesis imperfecta (OI) in the last few years. There has always been a safety concern regarding zoledronate’s use due to a paucity of studies. The current study is a retrospective evaluation of children with OI on the short- and long-term side effects of zoledronate and the frequency of fractures per year after the drug was introduced.

Methods:

A total of 26 children diagnosed with OI, with a median age of 84 (45–121) months were enrolled in the study. They received cyclical zoledronate for a median duration of 36 (11–61) months at quarterly intervals between January 2008 and December 2014. Safety evaluation involved assessment of its short- and long-term effects in addition to the frequency of fractures after its usage.

Results:

One (3%) neonate had symptomatic hypocalcemia 15 days after the infusion. Three children (11%) had acute phase reactions. None had long-term side effects, including osteonecrosis of the jaw, in our 7-year experience. OI of types III and IV (total of 22) had significant reductions in the number of fractures (p<0.05).

Conclusions:

Further long-duration studies are necessary to evaluate the longterm safety of zoledronate.

Keywords: bisphosphonates (BPs); bowing of bones; fractures; hypocalcemia; magnetic resonance imaging (MRI); metaphyseal bands; paediatric osteoporosis; zebra lines

Corresponding author: Inusha Panigrahi, MD, DM, Additional Professor and Incharge, Genetic-Metabolic unit, Department of Pediatrics, Advanced Pediatric Centre, Post Graduate Institute of Medical Education and Research, Chandigarh, India, Phone: +91-7087008319

Author contributions: Chanchal Kumar: conceptualised the study, collected the data, did statistical analysis and drafted the initial manuscript and approved the final manuscript. Inusha Panigrahi: conceptualized and designed the retrospective analysis, designed the data collection tool, analysed the data, critically reviewed the manuscript and approved the final manuscript. Abhishek Somasekhara Aradhya: assisted in designing the study and data collection, analysed the data, critically reviewed the manuscript and approved the final manuscript. Babu Lal Meena: assisted in designing the study and data collection, analysed the data, critically reviewed the manuscript and approved the final manuscript. Niranjan Khandelwal: assisted in designing the study, analysed the radiological data, critically reviewed the manuscript and approved the final manuscript. All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.
Research funding: None declared.
Employment or leadership: None declared.
Honorarium: None declared.
Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

References

1. Brown JJ, Zacharin MR. Safety and efficacy of intravenous zoledronic acid in paediatric osteoporosis. J Pediatr Endocrinol Metab 2009;22:55–63.10.1515/JPEM.2009.22.1.55Search in Google Scholar PubMed

2. Barros ER, Saraiva GL, de Oliveira TP, Lazaretti-Castro M. Safety and efficacy of a 1-year treatment with zoledronic acid compared to pamidronate in children with osteogenesis imperfecta. J Pediatr Endocrinol Metab 2012;25:485–91.10.1515/jpem-2012-0016Search in Google Scholar PubMed

3. Maines E, Monti E, Doro F, Morandi G, Cavarzere P, et al. Children and adolescents treated with neridronate for OI show no evidence of any osteonecrosis of the jaw. J Bone Miner Metab 2012;30:434–8.10.1007/s00774-011-0331-3Search in Google Scholar PubMed

4. Valadares ER, Carneiro TB, Santos PM, Oliveira AC, Zabel B. What is new in genetics and osteogenesis imperfect classification? J Pediatr (Rio J) 2014;90:536–41.10.1016/j.jped.2014.05.003Search in Google Scholar PubMed

5. Cole WG. The molecular pathology of osteogenesis imperfecta. Clin Orthop Relat Res 1997;343:235–48.10.1097/00003086-199710000-00034Search in Google Scholar

6. Dalle Carbonare L, Zanatta M, Gasparetto A, Valenti MT. Safety and tolerability of zoledronic acid and other bisphosphonates in osteoporosis management. Drug Healthc Patient Saf 2010;2:121–37.10.2147/DHPS.S6285Search in Google Scholar PubMed PubMed Central

7. Reid IR, Brown JP, Burckhardt P, Horowitz Z, Richardson P, et al. Intravenous zoledronic acid in postmenopausal women with low bone mineral density. N Engl J Med 2002;346:653–61.10.1056/NEJMoa011807Search in Google Scholar PubMed

8. Plotkin LI, Weinstein RS, Parfitt AM, Roberson PK, Manolagas SC, et al. Prevention of osteocyte and osteoblast apoptosis by bisphosphonates and calcitonin. J Clin Invest 1999;104:1363–74.10.1172/JCI6800Search in Google Scholar PubMed PubMed Central

9. Plotkin LI, Aguirre JI, Kousteni S, Manolagas SC, Bellido T. Bisphosphonates and estrogens inhibit osteocyte apoptosis via distinct molecular mechanisms downstream of extracellular signal-regulated kinase activation. J Biol Chem 2005;280: 7317–25.10.1074/jbc.M412817200Search in Google Scholar PubMed

10. Munns CF, Rajab MH, Hong J, Briody J, Högler W, et al. Acute phase response and mineral status following low dose intravenous zoledronic acid in children. Bone 2007;41:366–70.10.1016/j.bone.2007.05.002Search in Google Scholar PubMed

11. Högler W, Yap F, Little D, Ambler G, McQuade M, et al. Short-term safety assessment in the use of intravenous zoledronic acid in children. J Pediatr 2004;145:701–4.10.1016/j.jpeds.2004.06.066Search in Google Scholar PubMed

12. Nicolaou N, Agrawal Y, Padman M, Fernandes JA, Bell MJ. Changing pattern of femoral fractures in osteogenesis imperfecta with prolonged use of bisphosphonates. J Child Orthop 2012;6:21–7.10.1007/s11832-011-0380-0Search in Google Scholar PubMed PubMed Central

13. Sillence DO, Senn A, Danks DM. Genetic heterogeneity in osteogenesis imperfecta. J Med Genet 1979;16:101–16.10.1136/jmg.16.2.101Search in Google Scholar PubMed PubMed Central

14. Sillence DO. Osteogenesis imperfecta: an expanding panorama of variants. Clin Orthop 1981;159:11–25.10.1097/00003086-198109000-00004Search in Google Scholar

15. Warman ML, Cormier-Daire V, Hall C, Krakow D, Lachman R, et al. Nosology and classification of genetic skeletal disorders: 2010 revision. Am J Med Genet A 2011;155A:943–68.10.1002/ajmg.a.33909Search in Google Scholar PubMed PubMed Central

16. Chennuru S, Koduri J, Bauman MA. Risk factors for symptomatic hypocalcemia complicating treatment with zoledronic acid. Intern Med J 2008;38:635–7.10.1111/j.1445-5994.2007.01580.xSearch in Google Scholar PubMed

17. Black DM, Delmas PD, Eastell R, Reid IR, Boonen S, et al. Once-yearly zoledronic acid for treatment of postmenopausal osteoporosis: HORIZON Pivotal Fracture Trial. N Engl J Med 2007;356:1809–22.10.1056/NEJMoa067312Search in Google Scholar PubMed

18. Hewitt RE, Lissina A, Green AE, Slay ES, Price DA, et al. The bisphosphonate acute phase response: rapid and copious production of proinflammatory cytokines by peripheral blood gd T cells in response to aminobisphosphonates is inhibited by statins. Clin Exp Immunol 2005;39:101–11.10.1111/j.1365-2249.2005.02665.xSearch in Google Scholar PubMed PubMed Central

19. Bertoldo F, Pancheri S, Zenari S, Boldini S, Giovanazzi B, et al. Serum 25-hydroxyvitamin D levels modulate the acute phase response associated with the first nitrogen containing bisphosphonate infusion. J Bone Miner Res 2009;25:447–54.10.1359/jbmr.090819Search in Google Scholar PubMed

20. Meier RP, Perneger TV, Stern R, Rizzoli R, Peter RE. Increasing occurrence of atypical femoral fractures associated with bisphosphonate use. Arch Intern Med 2012;172:930–6.10.1001/archinternmed.2012.1796Search in Google Scholar PubMed

21. Fedele S, Kumar N, Davies R, Fiske J, Greening S, et al. Dental management of patients at risk of osteochemonecrosis of the jaws: a critical review. Oral Dis 2009;15:527–37.10.1111/j.1601-0825.2009.01581.xSearch in Google Scholar PubMed

22. Hennedige AH, Jayasinghe J, Khajeh J, Macfarlane TV. Systematic review on the incidence of bisphosphonate related osteonecrosis of the jaw in children diagnosed with osteogenesis imperfecta. J Oral Maxillofac Res 2013;4:e1.10.5037/jomr.2013.4401Search in Google Scholar PubMed PubMed Central

23. Brown JJ, Ramalingam L, Zacharin MR. Bisphosphonate-associated osteonecrosis of the jaw: does it occur in children? Clin Endocrinol (Oxf) 2008;68:863–7.10.1111/j.1365-2265.2008.03189.xSearch in Google Scholar PubMed

24. Lu Y, Zhao F, Ren X, Li Z, Yang X, et al. A rare case of osteogenesis imperfecta combined with complete tooth loss. J Pediatr Endocrinol Metab 2014;27:143–7.10.1515/jpem-2013-0069Search in Google Scholar PubMed

25. Panigrahi I, Das RR, Sharda S, Marwaha RK, Khandelwal N. Response to zolendronic acid in children with type III osteogenesis imperfecta. J Bone Miner Metab 2010;28:451–5.10.1007/s00774-009-0149-4Search in Google Scholar PubMed

26. Dwan K, Phillipi CA, Steiner RD, Basel D. Bisphosphonate therapy for osteogenesis imperfecta. Cochrane Database Syst Rev 2014;7:CD005088.10.1002/14651858.CD005088.pub3Search in Google Scholar PubMed

27. Renaud A, Aucourt J, Weill J, Bigot J, Dieux A, et al. Radiographic features of osteogenesis imperfecta. Insights Imaging 2013;4:417–29.10.1007/s13244-013-0258-4Search in Google Scholar PubMed PubMed Central

28. van Persijn van Meerten EL, Kroon HM, Papapoulos SE. Epi- and metaphyseal changes in children caused by administration of bisphosphanates. Radiology 1992;184:249–54.10.1148/radiology.184.1.1609087Search in Google Scholar PubMed

29. Al Muderis M, Azzopardi T, Cundy P. Zebra lines of Pamidronate therapy in children. J Bone Joint Surg Am 2007;89A:1511–6.10.2106/00004623-200707000-00015Search in Google Scholar

30. Rauch F, Travers R, Plotkin H, Glorieux FH. The effects of intravenous pamidronate on the bone tissue of children and adolescents with osteogenesis imperfecta. J Clin Invest 2002;110:1293–9.10.1172/JCI0215952Search in Google Scholar

31. Drake TM, Clarke BL, Khosla S. Bisphosphonates: mechanism of action and role in clinical practice. Mayo Clin Proc 2008;83:1032–45.10.4065/83.9.1032Search in Google Scholar PubMed PubMed Central

Received: 2015-8-31

Accepted: 2016-4-12

Published Online: 2016-5-28

Published in Print: 2016-8-1

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Articles in the same Issue

https://doi.org/10.1515/jpem-2015-0351

Keywords for this article

bisphosphonates (BPs); bowing of bones; fractures; hypocalcemia; magnetic resonance imaging (MRI); metaphyseal bands; paediatric osteoporosis; zebra lines