European Journal of Pediatrics

, Volume 177, Issue 6, pp 891–902 | Cite as

Pain and quality of life of children and adolescents with osteogenesis imperfecta over a bisphosphonate treatment cycle

  • Argerie Tsimicalis
  • Madalina Boitor
  • Catherine E. Ferland
  • Frank Rauch
  • Sylvie Le May
  • Jaimie Isabel Carrier
  • Tracy Ngheim
  • Claudette Bilodeau
Original Article


The objective was to describe the pain and quality of life among children and adolescents with any osteogenesis imperfecta (OI) type over one intravenous bisphosphonate treatment cycle from a child and parental perspective. A prospective, observational study was conducted, where children and adolescents evaluated their pain intensity, location, and quality, as well as quality of life before, 1 week after treatment, and 6 months later. Quality of life was also evaluated from the parental perspective at the same three time points. Thirty-three child/parent dyads participated. The results showed that pain intensity on the 0–10 self-report scale after the Zoledronate infusion (median = 0, range = 0–6) was not different from pre (median = 2, range = 0–10) and 6-months post-scores (median = 2, range = 0–8) (p = 0.170). Children and adolescents with OI reported experiencing pain mainly in the ankles and the anterior and posterior shoulders. They selected evaluative pain descriptors such as uncomfortable (n = 16, 48%) and annoying (n = 13, 39%). Children and adolescents’ functioning and quality of life did not change significantly across the bisphosphonate treatment cycle (p = 0.326), parents perceived an improvement immediately after the treatment compared to before (p = 0.016).

Conclusion: Children and adolescents with OI experience mild, yet complex pain localized across several body areas. There is little fluctuation in the pain intensity and functioning of children with OI undergoing bisphosphonate treatment.

What is Known:

• Acute and chronic musculoskeletal pain remains a major issue in OI.

• Pain has a negative impact on quality of life.

What is New:

• New and unpublished methods and findings describing the pain and quality of life of children and adolescents with OI over one intravenous bisphosphonate treatment cycle from a child- and parental-proxy perspective.

• Children and adolescents with OI experience pain intensity that is mild, yet complex in quality and localized across several body areas.


Pain Quality of life Osteogenesis imperfecta Bisphosphonate treatment Pediatrics 



Adolescent Pediatric Pain Tool


Faces Pain Scale–Revised


International Association for the Study of Pain




Osteogenesis imperfecta


Over the counter


Pediatric Quality of Life 4.0


Quality of life


Randomized controlled trials


Authors’ contributions

Madalina Boitor, a doctoral trainee, analyzed the data, interpreted the findings, and wrote the manuscript. Catherine Ferland designed the study as part of her postdoctoral training, reviewed the findings, and edited and reviewed the manuscript. Frank Rauch designed the study, was responsible for ethics, oversaw recruitment and data collection, reviewed the findings, and reviewed the manuscript. Sylvie Le May reviewed the findings and manuscript; offering her expertise in pain research with children. Jaimie Isabel Carrier, an undergraduate research trainee, recruited and collected data, participated in data analysis, reviewed the manuscript. Tracy Nghiem, a graduate research trainee, reviewed the findings, edited and reviewed the manuscript; offering her training expertise in pain in OI. Claudette Bilodeau recruited and collected data, supervised undergraduate trainee, participated in data analysis, reviewed the manuscript. Argerie Tsimicalis edited the study design, was responsible for ethics and budget, oversaw recruitment, data collection, and analysis, supervised staff and trainees, participated in data analysis and interpretation, and wrote, edited, and reviewed the manuscript.


Argerie Tsimicalis received research grants from Quebec Nursing Intervention Research Network (RRISIQ), Newton Foundation, Scotiabank®, and Tunis Temple.

Compliance with ethical statements

Conflict of interest

The authors declare that they have no conflict of interest.

Informed consent

All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2008 (5). Informed consent was obtained from all patients for being included in the study.


  1. 1.
    Al-Harthy M, Ohrbach R, Michelotti A, List T (2016) The effect of culture on pain sensitivity. J Oral Rehabil 43(2):81–88. CrossRefPubMedGoogle Scholar
  2. 2.
    Arponen H, Makitie O, Waltimo-Siren J (2014) Association between joint hypermobility, scoliosis, and cranial base anomalies in paediatric Osteogenesis imperfecta patients: a retrospective cross-sectional study. BMC Musculoskelet Disord 15:428CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Bishop N, Harrison R, Ahmed F, Shaw N, Eastell R, Campbell M, Knowles E, Hill C, Hall C, Chapman S, Sprigg A, Rigby A (2010) A randomized, controlled dose-ranging study of Risedronate in children with moderate and severe osteogenesis imperfecta. J Bone Miner Res 25(1):32–40. CrossRefPubMedGoogle Scholar
  4. 4.
    Bishop N, Adami S, Ahmed SF, Anton J, Arundel P, Burren CP, Devogelaer JP, Hangartner T, Hosszu E, Lane JM, Lorenc R, Makitie O, Munns CF, Paredes A, Pavlov H, Plotkin H, Raggio CL, Reyes ML, Schoenau E, Semler O, Sillence DO, Steiner RD (2013) Risedronate in children with osteogenesis imperfecta: a randomised, double-blind, placebo-controlled trial. Lancet 382(9902):1424–1432. CrossRefPubMedGoogle Scholar
  5. 5.
    Chevrel G, Schott AM, Fontanges E, Charrin JE, Lina-Granade G, Duboeuf F, Garnero P, Arlot M, Raynal C, Meunier PJ (2006) Effects of oral alendronate on BMD in adult patients with osteogenesis imperfecta: a 3-year randomized placebo-controlled trial. J Bone Miner Res 21(2):300–306. CrossRefPubMedGoogle Scholar
  6. 6.
    Corli O, Martoni AA, Porcu L, Roberto A, Pinto C, Torri V, Guglieri I, Zagonel V, Oncology ESP (2016) Non-clinical factors influencing pain intensity in cancer patients: socio-cultural-economic status, awareness of disease and the relation with the oncologist. Eur J Intern Med 33:E18–E19. CrossRefPubMedGoogle Scholar
  7. 7.
    Dahan-Oliel N, Oliel S, Tsimicalis A, Montpetit K, Rauch F, Dogba MJ (2016) Quality of life in osteogenesis imperfecta: a mixed-methods systematic review. Am J Med Genet A 170(1):62–76. CrossRefGoogle Scholar
  8. 8.
    Dogba MJ, Rauch F, Tre G, Glorieux FH, Bedos C (2014) Shaping and managing the course of a child's disease: parental experiences with osteogenesis imperfecta. Disabil Health J 7(3):343–349. CrossRefPubMedGoogle Scholar
  9. 9.
    Dwan K, Phillipi CA, Steiner RD, Basel D (2016) Bisphosphonate therapy for osteogenesis imperfecta. The Cochrane database of systematic reviews 10:CD005088. PubMedCrossRefGoogle Scholar
  10. 10.
    Eccleston C, Palermo TM, Williams AC, Lewandowski Holley A, Morley S, Fisher E, Law E (2014) Psychological therapies for the management of chronic and recurrent pain in children and adolescents. Cochrane Database of Syst Rev 5:CD003968. CrossRefGoogle Scholar
  11. 11.
    Eiser C, Varni JW (2013) Health-related quality of life and symptom reporting: similarities and differences between children and their parents. Eur J Pediatr 172(10):1299–1304. CrossRefPubMedGoogle Scholar
  12. 12.
    Fernandes AM, De Campos C, Batalha L, Perdigao A, Jacob E (2014) Pain assessment using the adolescent pediatric pain tool: a systematic review. Pain Res Manag 19(4):212–218CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Finan PH, Goodin BR, Smith MT (2013) The Association of Sleep and Pain: an update and a path forward. J Pain 14(12):1539–1552. CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Food Drug Aadministration. Center for Drug Evaluation and Research. Statistical review and evaluation - clinical studies: Zometa (zoledronic acid) intravenous injection (i.v.) 4 mg lyophilized powder. Treatment of children with osteogenesis imperfecta (OI).
  15. 15.
    Forlino A, Marini JC (2016) Osteogenesis imperfecta. Lancet 387(10028):1657–1671. CrossRefPubMedGoogle Scholar
  16. 16.
    Goesling J, Clauw DJ, Hassett AL (2013) Pain and depression: an integrative review of neurobiological and psychological factors. Curr Psychiat Rep 15(12):Artn 421. CrossRefGoogle Scholar
  17. 17.
    Harrington J, Sochett E, Howard A (2014) Update on the evaluation and treatment of osteogenesis imperfecta. Pediatr Clin N Am 61(6):1243–1257. CrossRefGoogle Scholar
  18. 18.
    Hill CL, Baird WO, Walters SJ (2014) Quality of life in children and adolescents with osteogenesis imperfecta: a qualitative interview based study. Health Qual Life Out 12:54. CrossRefGoogle Scholar
  19. 19.
    Jacob E, Mack AK, Savedra M, Van Cleve L, Wilkie DJ (2014) Adolescent pediatric pain tool for multidimensional measurement of pain in children and adolescents. Pain Manag Nurs 15(3):694–706. CrossRefPubMedGoogle Scholar
  20. 20.
    Letocha AD, Cintas HL, Troendle JF, Reynolds JC, Cann CE, Chernoff EJ, Hill SC, Gerber LH, Marini JC (2005) Controlled trial of pamidronate in children with types III and IV osteogenesis imperfecta confirms vertebral gains but not short-term functional improvement. J Bone Miner Res 20(6):977–986. CrossRefPubMedGoogle Scholar
  21. 21.
    Martin E, Shapiro JR (2007) Osteogenesis imperfecta: epidemiology and pathophysiology. Current Osteoporosis Reports 5(3):91–97CrossRefPubMedGoogle Scholar
  22. 22.
    McGrath PJ, Walco GA, Turk DC, Dworkin RH, Brown MT, Davidson K, Eccleston C, Finley GA, Goldschneider K, Haverkos L, Hertz SH, Ljungman G, Palermo T, Rappaport BA, Rhodes T, Schechter N, Scott J, Sethna N, Svensson OK, Stinson J, von Baeyer CL, Walker L, Weisman S, White RE, Zajicek A, Zeltzer L, PedImmpact (2008) Core outcome domains and measures for pediatric acute and chronic/recurrent pain clinical trials: PedIMMPACT recommendations. J Pain : Off J Am Pain Soc 9(9):771–783. CrossRefGoogle Scholar
  23. 23.
    McKiernan FE (2005) Musculoskeletal manifestations of mild osteogenesis imperfecta in the adult. Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA 16(12):1698–1702. CrossRefGoogle Scholar
  24. 24.
    Merskey H, Bogduk N, International Association for the Study of Pain. Task Force on Taxonomy (1994) Classification of chronic pain: descriptions of chronic pain syndromes and definitions of pain terms. IASP pressGoogle Scholar
  25. 25.
    Nghiem T, Louli J, Treherne SC, Anderson CE, Tsimicalis A, Lalloo C, Stinson JN, Thorstad K (2017) Pain experiences of children and adolescents with osteogenesis imperfecta an integrative review. Clin J Pain 33(3):271–280. PubMedCrossRefGoogle Scholar
  26. 26.
    Palermo TM, Chambers CT (2005) Parent and family factors in pediatric chronic pain and disability: an integrative approach. Pain 119(1–3):1–4. CrossRefPubMedGoogle Scholar
  27. 27.
    Palermo TM, Eccleston C (2009) Parents of children and adolescents with chronic pain. Pain 146(1–2):15–17. CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Rahim-Williams B, Riley JL 3rd, Williams AK, Fillingim RB (2012) A quantitative review of ethnic group differences in experimental pain response: do biology, psychology, and culture matter? Pain Med 13(4):522–540. CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Rauch F, Munns CF, Land C, Cheung M, Glorieux FH (2009) Risedronate in the treatment of mild pediatric osteogenesis imperfecta: a randomized placebo-controlled study. J Bone Miner Res 24(7):1282–1289. CrossRefPubMedGoogle Scholar
  30. 30.
    Sakkers R, Kok D, Engelbert R, van Dongen A, Jansen M, Pruijs H, Verbout A, Schweitzer D, Uiterwaal C (2004) Skeletal effects and functional outcome with olpadronate in children with osteogenesis imperfecta: a 2-year randomised placebo-controlled study. Lancet 363(9419):1427–1431. CrossRefPubMedGoogle Scholar
  31. 31.
    Savedra MC, Tesler MD, Holzemer WL, Brokaw P (1995) A strategy to assess the temporal dimension of pain in children and adolescents. Nurs Res 44(5):272-276CrossRefGoogle Scholar
  32. 32.
    Seikaly MG, Kopanati S, Salhab N, Waber P, Patterson D, Browne R, Herring JA (2005) Impact of alendronate on quality of life in children with osteogenesis imperfecta. J Pediatr Orthop 25(6):786–791CrossRefPubMedGoogle Scholar
  33. 33.
    Stinson JN, Kavanagh T, Yamada J, Gill N, Stevens B (2006) Systematic review of the psychometric properties, interpretability and feasibility of self-report pain intensity measures for use in clinical trials in children and adolescents. Pain 125(1–2):143–157. CrossRefPubMedGoogle Scholar
  34. 34.
    Stinson JN, Jibb LA, Nguyen C, Nathan PC, Maloney AM, Dupuis LL, Gerstle JT, Alman B, Hopyan S, Strahlendorf C, Portwine C, Johnston DL, Orr M (2013) Development and testing of a multidimensional iPhone pain assessment application for adolescents with cancer. J Med Internet Res 15(3):e51. CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Tessier S, Vuillemin A, Lemelle JL, Briancon S (2009) Psychometric properties of the French pediatric quality of life inventory version 4.0 (PedsQL (TM) 4.0) generic core scales. Eur Rev Appl Psychol 59(4):291–300. CrossRefGoogle Scholar
  36. 36.
    Trejo P, Rauch F (2016) Osteogenesis imperfecta in children and adolescents-new developments in diagnosis and treatment. Osteoporosis Int 27(12):3427–3437. CrossRefGoogle Scholar
  37. 37.
    Tsimicalis A, Denis-Larocque G, Michalovic A, Lepage C, Williams K, Yao TR, Palomo T, Dahan-Oliel N, Le May S, Rauch F (2016) The psychosocial experience of individuals living with osteogenesis imperfecta: a mixed-methods systematic review. Qual Life Res 25(8):1877–1896. CrossRefPubMedGoogle Scholar
  38. 38.
    Van Dijk FS, Sillence DO (2014) Osteogenesis imperfecta: clinical diagnosis, nomenclature and severity assessment. Am J Med Genet 164A(6):1470–1481. CrossRefPubMedGoogle Scholar
  39. 39.
    Varni JW, Seid M, Kurtin PS (2001) PedsQL (TM) 4.0: reliability and validity of the pediatric quality of life inventory (TM) version 4.0 generic core scales in healthy and patient populations. Med Care 39(8):800–812. CrossRefPubMedGoogle Scholar
  40. 40.
    Varni JW, Seid M, Knight TS, Burwinkle T, Brown J, Szer IS (2002) The PedsQL (TM) in pediatric rheumatology—reliability, validity, and responsiveness of the pediatric quality of life inventory (TM) generic core scales and rheumatology module. Arthritis Rheum 46(3):714–725. CrossRefPubMedGoogle Scholar
  41. 41.
    Vyskocil V, Pikner R, Kutilek T (2005) Effect of alendronate therapy in children with osteogenesis imperfecta. Joint Bone Spine 72(5):416–423. CrossRefPubMedGoogle Scholar
  42. 42.
    Ward LM, Rauch F, Whyte MP, D'Astous J, Gates PE, Grogan D, Lester EL, McCall RE, Pressly TA, Sanders JO, Smith PA, Steiner RD, Sullivan E, Tyerman G, Smith-Wright DL, Verbruggen N, Heyden N, Lombardi A, Glorieux FH (2011) Alendronate for the treatment of pediatric osteogenesis imperfecta: a randomized placebo-controlled study. J Clin Endocr Metab 96(2):355–364. CrossRefPubMedGoogle Scholar
  43. 43.
    Wilkie DJ, Holzemer WL, Tesler MD, Ward JA, Paul SM, Savedra MC (1990) Measuring pain quality: validity and reliability of children's and adolescents' pain language. Pain 41(2):151–159CrossRefPubMedGoogle Scholar
  44. 44.
    Wood C, von Baeyer CL, Bourrillon A, Dejos-Conant V, Clyti N, Abitbol V (2004) Self-assessment of immediate post-vaccination pain after two different MMR vaccines administered as a second dose in 4- to 6-year-old children. Vaccine 23(2):127–131. CrossRefPubMedGoogle Scholar
  45. 45.
    World Health Organization (2012) WHO guidelines on the pharmacological treatment of persisting pain in children with medical illnesses. 1. World Health Organization,Google Scholar
  46. 46.
    Zack P, Franck L, Devile C, Clark C (2005) Fracture and non-fracture pain in children with osteogenesis imperfecta. Acta Paediatr 94(9):1238–1242. CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Ingram School of NursingMcGill UniversityMontrealCanada
  2. 2.McGill University Health CentreMontrealCanada
  3. 3.Clinical ResearchShriners Hospitals for Children®-CanadaMontrealCanada
  4. 4.Department of AnesthesiaMcGill UniversityMontrealCanada
  5. 5.Department of PediatricsMcGill UniversityMontrealCanada
  6. 6.Faculty of NursingUniversity of MontrealMontrealCanada

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