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  • Clinical Research Article
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Standardized growth charts for children with osteogenesis imperfecta

Pediatric Research volume 94, pages 1075–1082 (2023)Cite this article

Abstract

Background

Osteogenesis imperfecta (OI) is associated with short stature, which is mild, severe and moderate in OI types I, III and IV, respectively. Standardized OI type- and sex-specific growth charts across all pediatric ages do not exist.

Methods

We assessed 573 individuals with OI (type I, III or IV), each with at least one height measurement between ages 3 months and 20 years (total 6523 observations). Analogous to the Centers for Disease Control pediatric growth charts, we generated OI type- and sex-specific growth charts for infants (ages 3–36 months) as well as children and adolescents (ages 2–20 years). Growth curves were fitted to the data using the LMS method and percentiles were smoothed.

Results

Age was associated with a decline in height z-scores (p < 0.001 for all OI types), which was more pronounced in females. Height multiplier curves were produced to predict adult height in children with OI. Among individuals with OI type I, those with COL1A1 pathogenic variants leading to haploinsufficiency were taller than those with COL1A1 or COL1A2 pathogenic variants not leading to haploinsufficiency.

Conclusion

Our standardized OI type- and sex-specific growth charts can be used to assess the growth of individuals with OI from infancy to adulthood.

Impact

  • Standardized osteogenesis imperfecta (OI) type- and sex-specific growth charts across all pediatric ages do not exist.

  • Our study is the first to generate OI type- and sex-specific growth charts across all pediatric ages.

  • Our height multiplier curves can be utilized to predict adult height in children with OI.

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Fig. 1: Height in individuals with OI types I, III and IV.
Fig. 2: Weight in individuals with OI types I, III and IV.
Fig. 3: Age-dependency of height z-scores for OI types I, III and IV.
Fig. 4: Multiplier curves for OI types I, III and IV from 0 years to adult height.
Fig. 5: Comparison of height curves for individuals with OI type I, III and IV from 2 years to adult height achievement, by affected gene.
Fig. 6: Comparison of height curves for individuals with OI type I from 2 years to adult height achievement, by presence or absence of variants in COL1A1 leading to haploinsufficiency.

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Data availability

The datasets generated during and/or analyzed during the current study are not publicly available due to privacy and ethical concerns, but are available from the corresponding author on reasonable request.

References

  1. Forlino, A. & Marini, J. C. Osteogenesis imperfecta. Lancet 387, 1657–1671 (2016).

    Article  CAS  PubMed  Google Scholar 

  2. Robinson, M.-E. & Rauch, F. Mendelian bone fragility bisorders. Bone 126, 11–17 (2019).

    Article  CAS  PubMed  Google Scholar 

  3. Trejo, P. & Rauch, F. Osteogenesis imperfecta in children and adolescents-new developments in diagnosis and treatment. Osteoporos. Int. 27, 3427–3437 (2016).

    Article  CAS  PubMed  Google Scholar 

  4. Jain, M. et al. Growth characteristics in individuals with osteogenesis imperfecta in North America: results from a multicenter study. Genet Med. 21, 275–283 (2019).

    Article  CAS  PubMed  Google Scholar 

  5. Marr, C., Seasman, A. & Bishop, N. Managing the patient with osteogenesis imperfecta: a multidisciplinary approach. J. Multidiscip. Healthc. 10, 145–155 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  6. Robinson, M. E., Rauch, D., Glorieux, F. H. & Rauch, F. Pubertal growth in osteogenesis imperfecta caused by pathogenic variants in Col1a1/Col1a2. Genet Med. 24, 1920–1926 (2022).

    Article  CAS  PubMed  Google Scholar 

  7. Graff, K. & Syczewska, M. Developmental charts for children with osteogenesis imperfecta, type I (body height, body weight and BMI). Eur. J. Pediatr. 176, 311–316 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  8. Barber, L. A. et al. Longitudinal growth curves for children with classical osteogenesis imperfecta (types III and IV) caused by structural pathogenic variants in type I collagen. Genet Med. 21, 1233–1239 (2019).

    Article  CAS  PubMed  Google Scholar 

  9. Paley, J. et al. The multiplier method for prediction of adult height. J. Pediatr. Orthop. 24, 732–737 (2004).

    Article  PubMed  Google Scholar 

  10. Paley, D., Matz, A. L., Kurland, D. B., Lamm, B. M. & Herzenberg, J. E. Multiplier method for prediction of adult height in patients with achondroplasia. J. Pediatr. Orthop. 25, 539–542 (2005).

    Article  PubMed  Google Scholar 

  11. Mortier, G. R. et al. Nosology and classification of genetic skeletal disorders: 2019 revision. Am. J. Med. Genet A 179, 2393–2419 (2019).

    Article  PubMed  Google Scholar 

  12. Bardai, G., Moffatt, P., Glorieux, F. H. & Rauch, F. DNA sequence analysis in 598 individuals with a clinical diagnosis of osteogenesis imperfecta: diagnostic yield and mutation spectrum. Osteoporos. Int. 27, 3607–3613 (2016).

    Article  CAS  PubMed  Google Scholar 

  13. Montpetit, K., Palomo, T., Glorieux, F. H., Fassier, F. & Rauch, F. Multidisciplinary treatment of severe osteogenesis imperfecta: functional outcomes at skeletal maturity. Arch. Phys. Med. Rehabil. 96, 1834–1839 (2015).

    Article  PubMed  Google Scholar 

  14. Robinson, M. E., Trejo, P., Palomo, T., Glorieux, F. H. & Rauch, F. Osteogenesis imperfecta: skeletal outcomes after bisphosphonate discontinuation at final height. J. Bone Miner. Res. 34, 2198–2204 (2019).

    Article  CAS  PubMed  Google Scholar 

  15. Fassier, F. Fassier-Duval telescopic system: how I do it? J. Pediatr. Orthop. 37, S48–S51 (2017).

    Article  PubMed  Google Scholar 

  16. Ogden, C. L. et al. Centers for Disease Control and Prevention 2000 growth charts for the United States: improvements to the 1977 National Center for Health Statistics Version. Pediatrics 109, 45–60 (2002).

    Article  PubMed  Google Scholar 

  17. Cole, T. J. Fitting smoothed centile curves to reference data. J. R. Stat. Soc. Ser. A (Stat. Soc.) 151, 385–418 (1988).

    Article  Google Scholar 

  18. Butler, M. G. et al. Growth charts for non-growth hormone treated Prader-Willi syndrome. Pediatrics 135, e126–e135 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  19. Cole, T. J. & Green, P. J. Smoothing reference centile curves: the LMS method and penalized likelihood. Stat. Med. 11, 1305–1319 (1992).

    Article  CAS  PubMed  Google Scholar 

  20. Germain-Lee, E. L. et al. Cross-sectional and longitudinal growth patterns in osteogenesis imperfecta: implications for clinical care. Pediatr. Res. 79, 489–495 (2016).

    Article  PubMed  Google Scholar 

  21. Zemel, B. S. et al. Growth charts for children with Down syndrome in the United States. Pediatrics 136, e1204–e1211 (2015).

    Article  PubMed  Google Scholar 

  22. Horton, W. A., Rotter, J. I., Rimoin, D. L., Scott, C. I. & Hall, J. G. Standard growth curves for achondroplasia. J. Pediatr. 93, 435–438 (1978).

    Article  CAS  PubMed  Google Scholar 

  23. Patel, P. et al. Growth charts for patients with Hunter syndrome. Mol. Genet Metab. Rep. 1, 5–18 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  24. Muschol, N. M. et al. Growth charts for patients with Sanfilippo syndrome (Mucopolysaccharidosis type III). Orphanet J. Rare Dis. 14, 93 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  25. Montano, A. M., Tomatsu, S., Brusius, A., Smith, M. & Orii, T. Growth charts for patients affected with Morquio A disease. Am. J. Med. Genet A 146A, 1286–1295 (2008).

    Article  PubMed  Google Scholar 

  26. Quartel, A. et al. Growth charts for individuals with Mucopolysaccharidosis VI (Maroteaux-Lamy syndrome). JIMD Rep. 18, 1–11 (2015).

    PubMed  Google Scholar 

  27. Ben Amor, I. M., Roughley, P., Glorieux, F. H. & Rauch, F. Skeletal clinical characteristics of osteogenesis imperfecta caused by haploinsufficiency mutations in Col1a1. J. Bone Min. Res. 28, 2001–2007 (2013).

    Article  Google Scholar 

  28. Ma, J. et al. Impact of vertebral fractures and glucocorticoid exposure on height deficits in children during treatment of leukemia. J. Clin. Endocrinol. Metab. 104, 213–222 (2019).

    Article  PubMed  Google Scholar 

  29. Rauch, F., Lalic, L., Roughley, P. & Glorieux, F. H. Relationship between genotype and skeletal phenotype in children and adolescents with osteogenesis imperfecta. J. Bone Min. Res. 25, 1367–1374 (2010).

    CAS  Google Scholar 

  30. Rauch, D. et al. Assessment of longitudinal bone growth in osteogenesis imperfecta using metacarpophalangeal pattern profiles. Bone 140, 115547 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Zeitlin, L., Rauch, F., Plotkin, H. & Glorieux, F. H. 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 111, 1030–1036 (2003).

    Article  PubMed  Google Scholar 

  32. Sanguinetti, C., Greco, F., De Palma, L., Specchia, N. & Falciglia, F. Morphological changes in growth-plate cartilage in osteogenesis imperfecta. J. Bone Joint Surg. Br. 72, 475–479 (1990).

    Article  CAS  PubMed  Google Scholar 

  33. Grafe, I. et al. Excessive transforming growth factor-beta signaling is a common mechanism in osteogenesis imperfecta. Nat. Med. 20, 670–675 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Tauer, J. T., Abdullah, S. & Rauch, F. Effect of anti-TGF-beta treatment in a mouse model of severe osteogenesis imperfecta. J. Bone Min. Res. 34, 207–214 (2019).

    Article  CAS  Google Scholar 

  35. Wang, W., Rigueur, D. & Lyons, K. M. TGFβ signaling in cartilage development and maintenance. Birth Defects Res. C. Embryo Today 102, 37–51 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Nicol, L. E. et al. Alterations of a serum marker of collagen X in growing children with osteogenesis imperfecta. Bone 149, 115990 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Palomo, T., Glorieux, F. H., Schoenau, E. & Rauch, F. Body composition in children and adolescents with osteogenesis imperfecta. J. Pediatr. 169, 232–237 (2016).

    Article  PubMed  Google Scholar 

  38. Tauer, J. T., Robinson, M. E. & Rauch, F. Osteogenesis imperfecta: new perspectives from clinical and translational research. JBMR 3, e10174 (2019).

    Google Scholar 

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Acknowledgements

We thank Michaela Durigova for organizational support.

Funding

This study was supported by the Shriners of North America and the Fonds de recherche du Québec – Santé. Shriners of North America and Fonds de recherche du Québec – Santé had no role in the design and conduct of the study.

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Authors and Affiliations

  1. Shriners Hospital for Children – Canada, McGill University, Montreal, QC, Canada

    Marie-Eve Robinson, Damian Rauch, Francis H. Glorieux & Frank Rauch

  2. Children’s Hospital of Eastern Ontario Research Institute, University of Ottawa, Ottawa, ON, Canada

    Marie-Eve Robinson

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  1. Marie-Eve Robinson
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  2. Damian Rauch
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  3. Francis H. Glorieux
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  4. Frank Rauch
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Contributions

M.-E.R. assisted with data analysis and interpretation, drafted the initial manuscript, and reviewed and revised the manuscript. D.R. collected the study data, completed the data analysis, assisted with the interpretation of the data, and reviewed and revised the manuscript. F.H.G. contributed patient information and reviewed and revised the manuscript. F.R. conceptualized and designed the study, contributed patient information, assisted with data analysis and interpretation, and reviewed and revised the manuscript. All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.

Corresponding author

Correspondence to Marie-Eve Robinson.

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Competing interests

M.-E.R. declares study grants to institution from Ascendis Biopharma and Ipsen Biopharmaceuticals and consultancy fees to institution from Ipsen Biopharmaceuticals and Ultragenyx. D.R. has no conflicts of interest to declare. F.H.G. declares consulting fees and research grants from Novartis, Amgen, Mereo Biopharma and Ultragenyx. F.R. reports study grants to institution from PreciThera Inc, Ultragenyx Inc and Catabasis.

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Robinson, ME., Rauch, D., Glorieux, F.H. et al. Standardized growth charts for children with osteogenesis imperfecta. Pediatr Res 94, 1075–1082 (2023). https://doi.org/10.1038/s41390-023-02550-0

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