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Osteogenesis imperfecta: Epidemiology and pathophysiology

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Abstract

Osteogenesis imperfecta (OI) is the most common of the inherited connective tissue disorders that primarily affect bone. However, it is a systemic disorder, as evidenced by the occurrence of ocular complications, dentinogenesis imperfecta, hearing loss, joint laxity, restrictive pulmonary disease, and short stature. The OI classification initially included four phenotypes (I–IV) involving COL1A1 and COL1A2 mutations. Three new phenotypes have been added, of which one, type VII, is the result of mutations of the cartilage-associated protein (CRTAP) gene. Investigation of recessive forms of OI particularly reported among South African blacks have revealed mutations involving both the CRTAP gene and the leucine proline-enriched proteoglycan 1 (LEPRE1) gene, each involved in collagen proline-3 hydroxylation. Issues related to the treatment of OI with bisphosphonates involve patient selection, evaluation of the results of treatment, and the duration of treatment. Also, questions exist regarding the difference in treatment response between children and adults with OI. Other treatment options, such as recombinant human parathyroid hormone (1–34), Rank ligand inhibitors, and stem cell technology, are being evaluated or are of future investigative interest.

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References and Recommended Reading

  1. Sillence DO, Rimoin DL: Classification of osteogenesis imperfecta. Lancet 1978, 8072:1041–1042.

    Article  Google Scholar 

  2. Glorieux FH, Rauch F, Plotkin H, et al.: Type V osteogenesis imperfecta: a new form of brittle bone disease. J Bone Miner Res 2000, 15:1650–1658.

    Article  PubMed  CAS  Google Scholar 

  3. Andersen PE Jr, Hauge M: Osteogenesis imperfecta: a genetic, radiological, and epidemiological study. Clin Genet 1989, 36:250–255.

    PubMed  Google Scholar 

  4. Orioli IM, Castilla EE, Barbosa-Neto JG: The birth prevalence rates for the skeletal dysplasias. J Med Genet 1986, 23:328–332.

    Article  PubMed  CAS  Google Scholar 

  5. Beighton P, Versfeld GA: On the paradoxically high relative prevalence of osteogenesis imperfecta type III in the black population of South Africa. Clin Genet 1985, 27:398–401.

    Article  PubMed  CAS  Google Scholar 

  6. Viljoen D, Beighton P: Osteogenesis imperfecta type III: an ancient mutation in Africa? Am J Med Genet 1987, 227:907–912.

    Article  Google Scholar 

  7. Fedarko NS, Moerike M, Brenner R, et al.: Extracellular matrix formation by osteoblasts from patients with osteogenesis imperfecta. J Bone Miner Res 1992, 7:921–930.

    PubMed  CAS  Google Scholar 

  8. Fedarko ND, D’Avis P, Frazier CR, et al.: Cell proliferation of human fibroblasts and osteoblasts in osteogenesis imperfecta: influence of age. J Bone Miner Res 1995, 10:1705–1712.

    PubMed  CAS  Google Scholar 

  9. Nishimura G, Haga N, Kitoh H, et al.: The phenotypic spectrum of COL2A1 mutations. Hum Mutat 2005, 26:36–43.

    Article  PubMed  CAS  Google Scholar 

  10. Rauch F, Travers R, Parfitt AM, Glorieux FH: Static and dynamic bone histomorphometry in children with osteogenesis imperfecta. Bone 2000, 26:581–589.

    Article  PubMed  CAS  Google Scholar 

  11. Makareeva E, Cabral WA, Marini JC, Leikin S: Molecular mechanism of α1(I)-osteogenesis imperfecta/Ehlers-Danlos syndrome: unfolding of an N-anchor domain at the N-terminal end of the type I collagen triple helix. J Biol Chem 2006, 281:6463–6470.

    Article  PubMed  CAS  Google Scholar 

  12. Marini JC, Forlino A, Cabral WA, et al.: Consortium for osteogenesis imperfecta mutations in the helical domain of type I collagen: regions rich in lethal mutations align with collagen binding sites for integrins and proteoglycans [review]. Hum Mutat 2007, 28:209–221.

    Article  PubMed  CAS  Google Scholar 

  13. Barnes AM, Chang W, Morello R, et al.: Deficiency of cartilage-associated protein in recessive lethal osteogenesis imperfecta. N Engl J Med 2006, 355:2757–2764.

    Article  PubMed  CAS  Google Scholar 

  14. Cabral WA, Chang W, Barnes AM, et al.: Prolyl 3-hydroxylase 1 deficiency causes a recessive metabolic bone disorder resembling lethal/severe osteogenesis imperfecta. Nat Genet 2007, 39:359–365.

    Article  PubMed  CAS  Google Scholar 

  15. Glorieux FH, Ward LM, Rauch F, et al.: Osteogenesis imperfecta type VI: a form of brittle bone disease with a mineralization defect. J Bone Miner Res 2002, 17:30–38.

    Article  PubMed  Google Scholar 

  16. Ward LM, Rauch F, Travers R, et al.: Osteogenesis imperfecta type VII: an autosomal recessive form of brittle bone disease. Bone 2002, 31:12–18.

    Article  PubMed  CAS  Google Scholar 

  17. Labuda M, Morissette J, Ward LM, et al.: Osteogenesis imperfecta type VII maps to the short arm of chromosome 3. Bone 2002, 31:19–25.

    Article  PubMed  CAS  Google Scholar 

  18. Rauch F, Glorieux FH: Treatment of children with osteogenesis imperfecta [review]. Curr Osteoporos Rep 2006, 4:159–164.

    Article  PubMed  Google Scholar 

  19. Letocha AD, Cintas HL, Troendle JF, et al.: 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 2005, 20:977–986.

    Article  PubMed  CAS  Google Scholar 

  20. Glorieux FH, Bishop NJ, Plotkin H, et al.: Cyclic administration of pamidronate in children with severe osteogenesis imperfecta. N Engl J Med 1998, 339:947–952.

    Article  PubMed  CAS  Google Scholar 

  21. Plotkin H, Rauch F, Bishop NJ, et al.: Pamidronate treatment of severe osteogenesis imperfecta in children under 3 years of age. J Clin Endocrinol Metab 2000, 85:1846–1850.

    Article  PubMed  CAS  Google Scholar 

  22. Devogelaer J, Coppin C: Osteogenesis imperfecta: current treatment options. Treat Endocrinol 2006, 5:229–242.

    Article  PubMed  CAS  Google Scholar 

  23. Rauch F, Travers R, Glorieux FH: Pamidronate in children with osteogenesis imperfecta: histomorphometric effects of long-term therapy. J Clin Endocrinol Metab 2006, 91:511–516.

    Article  PubMed  CAS  Google Scholar 

  24. Land C, Rauch F, Travers R, Glorieux FH: Osteogenesis imperfecta type VI in childhood and adolescence: effects of cyclical intravenous pamidronate treatment. Bone 2007, 40:638–644.

    Article  PubMed  CAS  Google Scholar 

  25. Shapiro JR, McCarthy EF, Rossiter K, et al.: The effect of intravenous pamidronate on bone mineral density, bone histomorphometry, and parameters of bone turnover in adults with type IA osteogenesis imperfecta. Calcif Tissue Int 2003, 72:103–112.

    Article  PubMed  CAS  Google Scholar 

  26. Chevrel G, Schott AM, Fontanges E, et al.: Effects of oral alendronate on BMD in adult patients with osteogenesis imperfecta: a 3-year randomized placebo-controlled trial. J Bone Miner Res 2006, 21:300–306.

    Article  PubMed  CAS  Google Scholar 

  27. Glorieux FH: Osteogenesis imperfecta. A disease of the osteoblast. Lancet 2001, 358(suppl):S45.

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. The Kennedy Krieger Institute, 707 North Broadway, Baltimore, MD, 21205, USA

    Jay R. Shapiro

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  1. Elizabeth Martin
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  2. Jay R. Shapiro
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Correspondence to Jay R. Shapiro.

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Martin, E., Shapiro, J.R. Osteogenesis imperfecta: Epidemiology and pathophysiology. Curr Osteoporos Rep 5, 91–97 (2007). https://doi.org/10.1007/s11914-007-0023-z

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  • DOI: https://doi.org/10.1007/s11914-007-0023-z

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