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Licensed Unlicensed Requires Authentication Published by De Gruyter July 25, 2015

Effects of bisphosphonates to treat osteoporosis in children with cerebral palsy: a meta-analysis

  • Min Jeong Kim , Soo-Nyung Kim , In-Sik Lee , Sochung Chung , Joonchul Lee , YouNa Yang , Inho Lee and Seong-Eun Koh EMAIL logo


Background: In childhood and adolescence, some patients with cerebral palsy (CP) have long-term limited mobility, which can lead to secondary osteoporosis, Prevention and treatment strategies have been evaluated for the management of low bone mineral density (BMD) and fragility fractures. Currently, however, there are no established guidelines for the stratification and individualization of therapeutic interventions. Recently, an increasing number of studies have reported on the use of bisphosphonates to increase BMD in various pediatric conditions, and bisphosphonates have been suggested as a method to treat osteoporosis and prevent fractures.

Purpose: We performed the current meta-analysis to assess the effects of bisphosphonates on increasing BMD in children who have CP with secondary osteoporosis.

Materials and methods: A search of PubMed, Cochrane, and Embase from inception to April 2014 was performed with the following keywords: (bone disease, metabolic OR osteoporosis OR osteopenia) AND (child OR pediatric OR adolescent) AND (cerebral palsy) AND (bisphosphonate). Four studies were ultimately included in the meta-analysis: one randomized, double-blinded, placebo-controlled study and three case-controlled studies.

Results: The Z-score of lumbar spine was significantly improved after bisphosphonates treatment compared with pre-treatment values (standardized mean difference [SMD], 0.799; 95% confidence interval [CI], 0.499–1.100; p<0.001). The Z-score of femur was also improved significantly compared with that of the baseline value (SMD, 0.748; 95% CI, 0.382–1.114; p<0.001).

Conclusions: Bisphosphonates have a significant effect on improving BMD in children with CP. Further standardization of treatment protocols including treatment dosage and duration needs to be established, and long-term follow up studies are needed.

Corresponding author: Seong-Eun Koh, MD, PhD, Department of Rehabilitation Medicine, Konkuk University Medical Center and Konkuk University School of Medicine, Konkuk University, 120-1 Neungdong-Ro, Gwangjin-Gu, Seoul, 143-729, Republic of Korea, Phone: +821047857151, Fax: +82220305379, E-mail:


1. Ward L, Tricco AC, Phuong P, Cranney A, Barrowman N, et al. Bisphosphonate therapy for children and adolescents with secondary osteoporosis. Cochrane Database Syst Rev 2007:CD005324.10.1002/14651858.CD005324.pub2Search in Google Scholar PubMed PubMed Central

2. Shaw NJ, White CP, Fraser WD, Rosenbloom L. Osteopenia in cerebral palsy. Arch Dis Child 1994;71:235–8.10.1136/adc.71.3.235Search in Google Scholar PubMed PubMed Central

3. Lee JJ, Lyne ED. Pathologic fractures in severely handicapped children and young adults. J Pediatr Orthop 1990;10:497–500.10.1097/01241398-199010040-00014Search in Google Scholar

4. Henderson RC, Lark RK, Gurka MJ, Worley G, Fung EB, et al. Bone density and metabolism in children and adolescents with moderate to severe cerebral palsy. Pediatrics 2002;110:e5.10.1542/peds.110.1.e5Search in Google Scholar PubMed

5. Tolman KG, Jubiz W, Sannella JJ, Madsen JA, Belsey RE, et al. Osteomalacia associated with anticonvulsant drug therapy in mentally retarded children. Pediatrics 1975;56:45–50.10.1542/peds.56.1.45Search in Google Scholar

6. Fehlings D, Switzer L, Agarwal P, Wong C, Sochett E, et al. Informing evidence-based clinical practice guidelines for children with cerebral palsy at risk of osteoporosis: a systematic review. Dev Med Child Neurol 2012;54:106–16.10.1111/j.1469-8749.2011.04091.xSearch in Google Scholar PubMed

7. Lewiecki EM, Gordon CM, Baim S, Leonard MB, Bishop NJ, et al. International Society for Clinical Densitometry 2007 Adult and Pediatric Official Positions. Bone 2008;43:1115–21.10.1016/j.bone.2008.08.106Search in Google Scholar PubMed

8. Baer MT, Kozlowski BW, Blyler EM, Trahms CM, Taylor ML, et al. Vitamin D, calcium, and bone status in children with developmental delay in relation to anticonvulsant use and ambulatory status. Am J Clin Nutr 1997;65:1042–51.10.1093/ajcn/65.4.1042Search in Google Scholar PubMed

9. Henderson RC, Lin PP, Greene WB. Bone-mineral density in children and adolescents who have spastic cerebral palsy. J Bone Joint Surg Am 1995;77:1671–81.10.2106/00004623-199511000-00005Search in Google Scholar PubMed

10. Henderson RC, Kairalla J, Abbas A, Stevenson RD. Predicting low bone density in children and young adults with quadriplegic cerebral palsy. Dev Med Child Neurol 2004;46:416–9.10.1017/S0012162204000672Search in Google Scholar

11. Munns CF, Cowell CT. Prevention and treatment of osteoporosis in chronically ill children. J Musculoskelet Neuronal Interact 2005;5:262–72.Search in Google Scholar

12. Iwasaki T, Nonoda Y, Ishii M. Long-term outcomes of children and adolescents who had cerebral palsy with secondary osteoporosis. Curr Med Res Opin 2012;28:737–47.10.1185/03007995.2011.645562Search in Google Scholar PubMed

13. Stevenson RD, Conaway M, Barrington JW, Cuthill SL, Worley G, et al. Fracture rate in children with cerebral palsy. Pediatr Rehabil 2006;9:396–403.10.1080/13638490600668061Search in Google Scholar PubMed

14. Henderson RC, Lark RK, Kecskemethy HH, Miller F, Harcke HT, et al. Bisphosphonates to treat osteopenia in children with quadriplegic cerebral palsy: a randomized, placebo-controlled clinical trial. J Pediatr 2002;141:644–51.10.1067/mpd.2002.128207Search in Google Scholar PubMed

15. Bianchi ML. How to manage osteoporosis in children. Best Pract Res Clin Rheumatol 2005;19:991–1005.10.1016/j.berh.2005.06.006Search in Google Scholar PubMed

16. Bachrach SJ, Kecskemethy HH, Harcke HT, Lark RK, Miller F, et al. Pamidronate treatment and posttreatment bone density in children with spastic quadriplegic cerebral palsy. J Clin Densitom 2006;9:167–74.10.1016/j.jocd.2005.11.003Search in Google Scholar PubMed

17. Falk MJ, Heeger S, Lynch KA, , DeCaro KR, Bohach D, et al. Intravenous bisphosphonate therapy in children with osteogenesis imperfecta. Pediatrics 2003;111:573–8.10.1542/peds.111.3.573Search in Google Scholar PubMed

18. Rauch F, Plotkin H, Zeitlin L, Glorieux FH. Bone mass, size, and density in children and adolescents with osteogenesis imperfecta: effect of intravenous pamidronate therapy. J Bone Miner Res 2003;18:610–4.10.1359/jbmr.2003.18.4.610Search in Google Scholar PubMed

19. Steelman J, Zeitler P. Treatment of symptomatic pediatric osteoporosis with cyclic single-day intravenous pamidronate infusions. J Pediatr 2003;142:417–23.10.1067/mpd.2003.137Search in Google Scholar PubMed

20. Plotkin H, Coughlin S, Kreikemeier R, Heldt K, Bruzoni M, et al. Low doses of pamidronate to treat osteopenia in children with severe cerebral palsy: a pilot study. Dev Med Child Neurol 2006;48:709–12.10.1017/S0012162206001526Search in Google Scholar PubMed

21. Paksu MS, Vurucu S, Karaoglu A, Karacalioglu AO, Polat A, et al. Osteopenia in children with cerebral palsy can be treated with oral alendronate. Childs Nerv Syst 2012;28:283–6.10.1007/s00381-011-1576-9Search in Google Scholar PubMed

22. Hough JP, Boyd RN, Keating JL. Systematic review of interventions for low bone mineral density in children with cerebral palsy. Pediatrics 2010;125:e670–8.10.1542/peds.2009-0292Search in Google Scholar

23. Houlihan CM, Stevenson RD. Bone density in cerebral palsy. Phys Med Rehabil Clin N Am 2009;20:493–508.10.1016/j.pmr.2009.04.004Search in Google Scholar

24. Henderson RC, Kairalla JA, Barrington JW, Abbas A, Stevenson RD. Longitudinal changes in bone density in children and adolescents with moderate to severe cerebral palsy. J Pediatr 2005;146:769–75.10.1016/j.jpeds.2005.02.024Search in Google Scholar

25. Reid DM, Hughes RA, Laan RF, Sacco-Gibson NA, Wenderoth DH, et al. Efficacy and safety of daily risedronate in the treatment of corticosteroid-induced osteoporosis in men and women: a randomized trial. European Corticosteroid-Induced Osteoporosis Treatment Study. J Bone Miner Res 2000;15:1006–13.10.1359/jbmr.2000.15.6.1006Search in Google Scholar

26. Plotkin H, Rauch F, Bishop NJ, Montpetit K, Ruck-Gibis J, et al. Pamidronate treatment of severe osteogenesis imperfecta in children under 3 years of age. J Clin Endocrinol Metab 2000;85:1846–50.Search in Google Scholar

27. Iwasaki T, Takei K, Nakamura S, Hosoda N, Yokota Y, et al. Secondary osteoporosis in long-term bedridden patients with cerebral palsy. Pediatr Int 2008;50:269–75.10.1111/j.1442-200X.2008.02571.xSearch in Google Scholar

28. Bass SL, Naughton G, Saxon L, Iuliano-Burns S, Daly R, et al. Exercise and calcium combined results in a greater osteogenic effect than either factor alone: a blinded randomized placebo-controlled trial in boys. J Bone Miner Res 2007;22:458–64.10.1359/jbmr.061201Search in Google Scholar

29. Caulton JM, Ward KA, Alsop CW, Dunn G, Adams JE, et al. A randomised controlled trial of standing programme on bone mineral density in non-ambulant children with cerebral palsy. Arch Dis Child 2004;89:131–5.10.1136/adc.2002.009316Search in Google Scholar

30. Chad KE, Bailey DA, McKay HA, Zello GA, Snyder RE. The effect of a weight-bearing physical activity program on bone mineral content and estimated volumetric density in children with spastic cerebral palsy. J Pediatr 1999;135:115–7.10.1016/S0022-3476(99)70340-9Search in Google Scholar

31. Kilpinen-Loisa P, Nenonen H, Pihko H, Makitie O. High-dose vitamin D supplementation in children with cerebral palsy or neuromuscular disorder. Neuropediatrics 2007;38:167–72.10.1055/s-2007-990266Search in Google Scholar PubMed

32. Ali O, Shim M, Fowler E, Greenberg M, Perkins D, et al. Growth hormone therapy improves bone mineral density in children with cerebral palsy: a preliminary pilot study. J Clin Endocrinol Metab 2007;92:932–7.10.1210/jc.2006-0385Search in Google Scholar PubMed

33. Sugiyama T, Takaki T, Saito T, Taguchi T. Vitamin K therapy for cortical bone fragility caused by reduced mechanical loading in a child with hemiplegia. J Musculoskelet Neuronal Interact 2007;7:219–23.Search in Google Scholar

34. Allington N, Vivegnis D, Gerard P. Cyclic administration of pamidronate to treat osteoporosis in children with cerebral palsy or a neuromuscular disorder: a clinical study. Acta Orthop Belg 2005;71:91–7.Search in Google Scholar

35. Unal E, Abaci A, Bober E, Buyukgebiz A. Efficacy and safety of oral alendronate treatment in children and adolescents with osteoporosis. J Pediatr Endocrinol Metab 2006;19:523–8.Search in Google Scholar

36. Ruck J, Chabot G, Rauch F. Vibration treatment in cerebral palsy: a randomized controlled pilot study. J Musculoskelet Neuronal Interact 2010;10:77–83.Search in Google Scholar

37. Wren TA, Lee DC, Hara R, Rethlefsen SA, Kay RM, et al. Effect of high-frequency, low-magnitude vibration on bone and muscle in children with cerebral palsy. J Pediatr Orthop 2010;30:732–8.10.1097/BPO.0b013e3181efbabcSearch in Google Scholar PubMed PubMed Central

38. Eisenberg S, Zuk L, Carmeli E, Katz-Leurer M. Contribution of stepping while standing to function and secondary conditions among children with cerebral palsy. Pediatr Phys Ther 2009;21:79–85.10.1097/PEP.0b013e31818f57f2Search in Google Scholar PubMed

39. Conwell LS, Chang AB. Bisphosphonates for osteoporosis in people with cystic fibrosis. Cochrane Database Syst Rev 2009:CD002010.10.1002/14651858.CD002010.pub2Search in Google Scholar PubMed

40. Noguera A, Ros JB, Pavia C, Alcover E, Valls C, et al. Bisphosphonates, a new treatment for glucocorticoid-induced osteoporosis in children. J Pediatr Endocrinol Metab 2003;16:529–36.10.1515/JPEM.2003.16.4.529Search in Google Scholar

41. Phillipi CA, Remmington T, Steiner RD. Bisphosphonate therapy for osteogenesis imperfecta. Cochrane Database Syst Rev 2008:CD005088.10.1002/14651858.CD005088.pub2Search in Google Scholar PubMed

42. Salehpour S, Tavakkoli S. Cyclic pamidronate therapy in children with osteogenesis imperfecta. J Pediatr Endocrinol Metab 2010;23:73–80.10.1515/JPEM.2010.23.1-2.73Search in Google Scholar

43. Glorieux FH, Bishop NJ, Plotkin H, Chabot G, Lanoue G, et al. Cyclic administration of pamidronate in children with severe osteogenesis imperfecta. N Engl J Med 1998;339:947–52.10.1056/NEJM199810013391402Search in Google Scholar PubMed

44. Simmons J, Zeitler P, Steelman J. Advances in the diagnosis and treatment of osteoporosis. Adv Pediatr 2007;54:85–114.10.1016/j.yapd.2007.03.007Search in Google Scholar PubMed

45. Binkley T, Johnson J, Vogel L, Kecskemethy H, Henderson R, et al. Bone measurements by peripheral quantitative computed tomography (pQCT) in children with cerebral palsy. J Pediatr 2005;147:791–6.10.1016/j.jpeds.2005.07.014Search in Google Scholar PubMed

46. Harcke HT, Taylor A, Bachrach S, Miller F, Henderson RC. Lateral femoral scan: an alternative method for assessing bone mineral density in children with cerebral palsy. Pediatr Radiol 1998;28:241–6.10.1007/s002470050341Search in Google Scholar PubMed

47. Rubin C, Judex S, Qin YX. Low-level mechanical signals and their potential as a non-pharmacological intervention for osteoporosis. Age Ageing 2006;35(Suppl 2):ii32–ii6.10.1093/ageing/afl082Search in Google Scholar PubMed

48. Grissom LE, Kecskemethy HH, Bachrach SJ, McKay C, Harcke HT. Bone densitometry in pediatric patients treated with pamidronate. Pediatr Radiol 2005;35:511–7.10.1007/s00247-004-1393-3Search in Google Scholar PubMed

Received: 2014-12-22
Accepted: 2015-5-22
Published Online: 2015-7-25
Published in Print: 2015-11-1

©2015 by De Gruyter

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