Pain and quality of life of children and adolescents with osteogenesis imperfecta over a bisphosphonate treatment cycle
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).
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• New and unpublished methods and findings describing the pain and quality of life of children and adolescents with OI over one intravenous bisphosphonate treatment cycle from a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.
KeywordsPain Quality of life Osteogenesis imperfecta Bisphosphonate treatment Pediatrics
Adolescent Pediatric Pain Tool
Faces Pain Scale–Revised
International Association for the Study of Pain
Over the counter
Pediatric Quality of Life 4.0
Quality of life
Randomized controlled trials
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.
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.
- 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. https://doi.org/10.1359/jbmr.090712 CrossRefPubMedGoogle Scholar
- 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. https://doi.org/10.1016/S0140-6736(13)61091-0 CrossRefPubMedGoogle Scholar
- 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. https://doi.org/10.1359/Jbmr.051015 CrossRefPubMedGoogle Scholar
- 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. https://doi.org/10.1016/j.ejim.2016.04.019 CrossRefPubMedGoogle Scholar
- 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. https://doi.org/10.1002/14651858.CD003968.pub4 CrossRefGoogle Scholar
- 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). http://www.fda.gov/downloads/drugs/developmentapprovalprocess/developmentresources/ucm072901.pdf
- 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. https://doi.org/10.1359/JBMR.050109 CrossRefPubMedGoogle Scholar
- 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. https://doi.org/10.1016/j.jpain.2008.04.007 CrossRefGoogle Scholar
- 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. https://doi.org/10.1007/s00198-005-1905-5 CrossRefGoogle Scholar
- 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
- 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. https://doi.org/10.1111/j.1526-4637.2012.01336.x CrossRefPubMedPubMedCentralGoogle Scholar
- 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. https://doi.org/10.1016/S0140-6736(04)16101-1 CrossRefPubMedGoogle Scholar
- 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. https://doi.org/10.1016/j.pain.2006.05.006 CrossRefPubMedGoogle Scholar
- 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. https://doi.org/10.2196/jmir.2350 CrossRefPubMedPubMedCentralGoogle Scholar
- 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. https://doi.org/10.1007/s11136-016-1247-0 CrossRefPubMedGoogle Scholar
- 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. https://doi.org/10.1002/art.10095 CrossRefPubMedGoogle Scholar
- 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. https://doi.org/10.1210/jc.2010-0636 CrossRefPubMedGoogle Scholar
- 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. https://doi.org/10.1016/j.vaccine.2004.08.029 CrossRefPubMedGoogle Scholar
- 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