Background/Aims: Pamidronate is widely used to treat pediatric patients with osteogenesis imperfecta (OI). We aimed at delineating the effects of monthly pamidronate therapy on the growth of different body segments in prepubertal OI patients. Methods: The study included 14 prepubertal patients (12 boys, 2 girls) with mild forms of OI (type I and IV). The mean age at treatment start was 7:8 years:months (3:7–11:0). Pamidronate was given as monthly intravenous infusions. The patients were measured 1 year before, at treatment start and 1 and 2 years after treatment start. Results: Height standard deviation score (SDS) and sitting height SDS significantly increased (p < 0.05) during the first year of treatment when compared to the pre-treatment year. No further improvement was detected during the second year of treatment. However, when plotted on disease-specific growth charts (untreated patients with the same OI types), height gain was significant during the first (p < 0.001) and second (p < 0.05) years of treatment. All patients increased their bone mineral density throughout the follow-up. Conclusion: Monthly pamidronate improves the growth of prepubertal patients with mild OI, where the most prominent growth stimulation is seen in the upper body segment.

Keywords:
Osteogenesis imperfecta, Bisphosphonate, Vertebral growth
1.
Roughley PJ, Rauch F, Glorieux FH: Osteogenesis imperfecta – clinical and molecular diversity. Eur Cell Mater 2003;5:41–47, discussion 47.
2.
Astrom E, Soderhall S: Beneficial effect of bisphosphonate during five years of treatment of severe osteogenesis imperfecta. Acta Paediatr 1998;87:64–68.
3.
Astrom E, Soderhall S: Beneficial effect of long term intravenous bisphosphonate treatment of osteogenesis imperfecta. Arch Dis Child 2002;86:356–364.
4.
Brumsen C, Hamdy NA, Papapoulos SE: Long-term effects of bisphosphonates on the growing skeleton. Studies of young patients with severe osteoporosis. Medicine (Baltimore) 1997;76:266–283.
5.
Glorieux FH, Bishop NJ, Plotkin H, Chabot G, Lanoue G, Travers R: Cyclic administration of pamidronate in children with severe osteogenesis imperfecta. N Engl J Med 1998;339:947–952.
6.
Lee YS, Low SL, Lim LA, Loke KY: Cyclic pamidronate infusion improves bone mineralisation and reduces fracture incidence in osteogenesis imperfecta. Eur J Pediatr 2001;160:641–644.
7.
Plotkin H, Rauch F, Bishop NJ, Montpetit K, Ruck-Gibis J, Travers R, Glorieux FH: Pamidronate treatment of severe osteogenesis imperfecta in children under 3 years of age. J Clin Endocrinol Metab 2000;85:1846–1850.
8.
Vetter U, Pontz B, Zauner E, Brenner RE, Spranger J: Osteogenesis imperfecta: a clinical study of the first ten years of life. Calcif Tissue Int 1992;50:36–41.
9.
Zeitlin L, Rauch F, Plotkin H, Glorieux FH: Height and weight development during four years of therapy with cyclical intravenous pamidronate in children and adolescents with osteogenesis imperfecta types I, III, and IV. Pediatrics 2003;111:1030–1036.
10.
Camacho NP, Raggio CL, Doty SB, Root L, Zraick V, Ilg WA, Toledano TR, Boskey AL: A controlled study of the effects of alendronate in a growing mouse model of osteogenesis imperfecta. Calcif Tissue Int 2001;69:94–101.
11.
McCarthy EA, Raggio CL, Hossack MD, Miller EA, Jain S, Boskey AL, Camacho NP: Alendronate treatment for infants with osteogenesis imperfecta: demonstration of efficacy in a mouse model. Pediatr Res 2002;52:660–670.
12.
Pataki A, Muller K, Green JR, Ma YF, Li QN, Jee WS: Effects of short-term treatment with the bisphosphonates zoledronate and pamidronate on rat bone: a comparative histomorphometric study on the cancellous bone formed before, during, and after treatment. Anat Rec 1997;249:458–468.
13.
Heino TJ, Chagin AS, Takigawa M, Savendahl L: Effects of alendronate and pamidronate on cultured rat metatarsal bones: failure to prevent dexamethasone-induced growth retardation. Bone 2008;42:702–709.
14.
Castillo H, Samson-Fang L: Effects of bisphosphonates in children with osteogenesis imperfecta: an AACPDM systematic review. Dev Med Child Neurol 2009;51:17–29.
15.
Delamarre-Van de Waal H: Secular trend of timing of puberty; in Delamarre-Van de Waal H (ed): Abnormalities in Puberty. Basel, Karger, 2005, pp 1–14.
16.
Sillence DO, Senn A, Danks DM: Genetic heterogeneity in osteogenesis imperfecta. J Med Genet 1979;16:101–116.
17.
Astrom E, Jorulf H, Soderhall S: Intravenous pamidronate treatment of infants with severe osteogenesis imperfecta. Arch Dis Child 2007;92:332–338.
18.
Albertsson-Wikland K, Luo ZC, Niklasson A, Karlberg J: Swedish population-based longitudinal reference values from birth to 18 years of age for height, weight and head circumference. Acta Paediatr 2002;91:739–754.
19.
Gatti D, Antoniazzi F, Prizzi R, Braga V, Rossini M, Tato L, Viapiana O, Adami S: Intravenous neridronate in children with osteogenesis imperfecta: a randomized controlled study. J Bone Miner Res 2005;20:758–763.
20.
Sakkers R, Kok D, Engelbert R, van Dongen A, Jansen M, Pruijs H, Verbout A, Schweitzer D, Uiterwaal C: Skeletal effects and functional outcome with olpadronate in children with osteogenesis imperfecta: a 2-year randomised placebo-controlled study. Lancet 2004;363:1427–1431.
21.
Antoniazzi F, Zamboni G, Lauriola S, Donadi L, Adami S, Tato L: Early bisphosphonate treatment in infants with severe osteogenesis imperfecta. J Pediatr 2006;149:174–179.
22.
Lund AM, Muller J, Skovby F: Anthropometry of patients with osteogenesis imperfecta. Arch Dis Child 1999;80:524–528.
23.
Arikoski P, Silverwood B, Tillmann V, Bishop NJ: Intravenous pamidronate treatment in children with moderate to severe osteogenesis imperfecta: assessment of indices of dual-energy X-ray absorptiometry and bone metabolic markers during the first year of therapy. Bone 2004;34:539–546.
24.
Zacharin M, Kanumakala S: Pamidronate treatment of less severe forms of osteogenesis imperfecta in children. J Pediatr Endocrinol Metab 2004;17:1511–1517.
25.
Land C, Rauch F, Munns CF, Sahebjam S, Glorieux FH: Vertebral morphometry in children and adolescents with osteogenesis imperfecta: effect of intravenous pamidronate treatment. Bone 2006;39:901–906.
26.
Brown JJ, Zacharin MR: Safety and efficacy of intravenous zoledronic acid in paediatric osteoporosis. J Pediatr Endocrinol Metab 2009;22:55–63.
27.
Dimeglio LA, Ford L, McClintock C, Peacock M: A comparison of oral and intravenous bisphosphonate therapy for children with osteogenesis imperfecta. J Pediatr Endocrinol Metab 2005;18:43–53.
28.
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;72:313–318.
29.
Vallo A, Rodriguez-Leyva F, Rodriguez Soriano J: Osteogenesis imperfecta: anthropometric, skeletal and mineral metabolic effects of long-term intravenous pamidronate therapy. Acta Paediatr 2006;95:332–339.
30.
Bachrach LK, Ward LM: Clinical review 1: bisphosphonate use in childhood osteoporosis. J Clin Endocrinol Metab 2009;94:400–409.
© 2011 S. Karger AG, Basel
2011
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.