Skip to main content

Advertisement

SpringerLink
Log in

Recent Advances in Osteogenesis Imperfecta

  • Review
  • Published:
Calcified Tissue International Aims and scope Submit manuscript

Abstract

“Osteogenesis imperfecta” is a term used to describe a group of genetic disorders of variable phenotype usually defined by recurrent fractures, low bone mass, and skeletal fragility. Most cases are associated with mutations in one of the type I collagen genes, but in recent years several other forms have been identified with recessive inheritance. In most instances the latter result from mutations in genes encoding proteins involved in type I collagen’s complex posttranslational modification or in genes regulating bone matrix homeostasis. This article reviews the recent discoveries and an approach to classification and diagnosis. Bisphosphonates are widely used in patients with osteogenesis imperfecta, but some important questions about their optimal usage, their utility in children and adults with milder phenotypes, and their potential adverse effects are not yet resolved.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Marini JC, Forlino A, Cabral WA, Barnes AM, San Antonio JD, Milgrom S, Hyland JC, Körkkö J, Prockop DJ, De Paepe A, Coucke P, Symoens S, Glorieux FH, Roughley PJ, Lund AM, Kuurila-Svahn K, Hartikka H, Cohn DH, Krakow D, Mottes M, Schwarze U, Chen D, Yang K, Kuslich C, Troendle J, Dalgleish R, Byers PH (2007) 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. Hum Mutat 28:209–221

    Article  PubMed  CAS  Google Scholar 

  2. Canty EG, Kadler KE (2005) Procollagen trafficking, processing and fibrillogenesis. J Cell Sci 118:1341–1353

    Article  PubMed  CAS  Google Scholar 

  3. Krane SM (2008) The importance of proline residues in the structure, stability and susceptibility to proteolytic degradations of collagens. Amino Acids 35:703–710

    Article  PubMed  CAS  Google Scholar 

  4. Sillence DO, Senn A, Danks DM (1979) Genetic heterogeneity in osteogenesis imperfecta. J Med Genet 16:101–116

    Article  PubMed  CAS  Google Scholar 

  5. Warman ML, Cormier-Daire V, Hall C, Krakow D, Lachman R, LeMerrer M, Mortier G, Mundlos S, Nishimura G, Rimoin DL, Robertson S, Savarirayan R, Sillence D, Spranger J, Unger S, Zabel B, Superti-Furga A (2011) Nosology and classification of genetic skeletal disorders: 2010 revision. Am J Med Genet 155A:943–968

    Article  PubMed  Google Scholar 

  6. Cundy T, Horne A, Bolland M, Gamble G, Davidson J (2007) Bone formation markers in adults with mild osteogenesis imperfecta. Clin Chem 53:1109–1114

    Article  PubMed  CAS  Google Scholar 

  7. Rauch F, Lalic L, Roughley P, Glorieux FH (2010) Genotype–phenotype correlations in nonlethal osteogenesis imperfecta caused by mutations in the helical domain of collagen type I. Eur J Hum Genet 18:642–647

    Article  PubMed  CAS  Google Scholar 

  8. Rauch F, Lalic L, Roughley P, Glorieux FH (2010) Relationship between genotype and skeletal phenotype in children and adolescents with osteogenesis imperfecta. J Bone Miner Res 25:1367–1374

    PubMed  CAS  Google Scholar 

  9. Semler O, Cheung MS, Glorieux FH, Rauch F (2010) Wormian bones in osteogenesis imperfecta: correlation to clinical findings and genotype. Am J Med Genet A 152:1681–1687

    Google Scholar 

  10. Cheung MS, Arponen H, Roughley P, Azouz ME, Glorieux FH, Waltimo-Siren J, Rauch F (2011) Cranial base abnormalities in osteogenesis imperfecta: phenotypic and genotypic determinants. J Bone Miner Res 26:405–413

    Article  PubMed  Google Scholar 

  11. Faqeih E, Roughley P, Glorieux FH, Rauch F (2009) Osteogenesis imperfecta type III with intracranial hemorrhage and brachydactyly associated with mutations in exon 49 of COL1A2. Am J Med Genet A 149:461–465

    Google Scholar 

  12. Lindahl K, Barnes AM, Fratzl-Zelman N, Whyte MP, Hefferan TE, Makareeva E, Brusel M, Yaszemski MJ, Rubin CJ, Kindmark A, Roschger P, Klaushofer K, McAlister WH, Mumm S, Leikin S, Kessler E, Boskey AL, Ljunggren O, Marini JC (2011) COL1A1 C-propeptide cleavage site mutations cause high bone mass osteogenesis imperfecta. Hum Mutat 32:598–609

    Article  PubMed  CAS  Google Scholar 

  13. Glorieux FH, Rauch F, Plotkin H, Ward L, Travers R, Roughley P, Lalic L, Glorieux DF, Fassier F, Bishop NJ (2000) Type V osteogenesis imperfecta: a new form of brittle bone disease. J Bone Miner Res 15:1650–1658

    Article  PubMed  CAS  Google Scholar 

  14. Cheung MS, Glorieux FH, Rauch F (2007) Natural history of hyperplastic callus formation in osteogenesis imperfecta type V. J Bone Miner Res 22:1181–1186

    Article  PubMed  Google Scholar 

  15. Morello R, Bertin TK, Chen Y, Hicks J, Tonachini L, Monticone M, Castagnola P, Rauch F, Glorieux FH, Vranka J, Bachinger HP, Pace JM, Schwarze U, Byers PH, Weis M, Fernandes RJ, Eyre DR, Yao Z, Boyce BF, Lee B (2006) CRTAP is required for prolyl 3- hydroxylation and mutations cause recessive osteogenesis imperfecta. Cell 127:291–304

    Article  PubMed  CAS  Google Scholar 

  16. Cabral WA, Chang W, Barnes AM, Weis M, Scott MA, Leikin S, Makareeva E, Kuznetsova NV, Rosenbaum KN, Tifft CJ, Bulas DI, Kozma C, Smith PA, Eyre DR, Marini JC (2007) Prolyl 3-hydroxylase 1 deficiency causes a recessive metabolic bone disorder resembling lethal/severe osteogenesis imperfecta. Nat Genet 39:359–365

    Article  PubMed  CAS  Google Scholar 

  17. Baldridge D, Schwarze U, Morello R, Lennington J, Bertin TK, Pace JM, Pepin MG, Weis M, Eyre DR, Walsh J, Lambert D, Green A, Robinson H, Michelson M, Houge G, Lindman C, Martin J, Ward J, Lemyre E, Mitchell JJ, Krakow D, Rimoin DL, Cohn DH, Byers PH, Lee B (2008) CRTAP and LEPRE1 mutations in recessive osteogenesis imperfecta. Hum Mutation 29:1435–1442

    Article  CAS  Google Scholar 

  18. Barnes AM, Carter EM, Cabral WA, Weis M, Chang W, Makareeva E, Leikin S, Rotimi CN, Eyre DR, Raggio CL, Marini JC (2010) Lack of cyclophilin B in osteogenesis imperfecta with normal collagen folding. N Engl J Med 362:521–528

    Article  PubMed  CAS  Google Scholar 

  19. Alanay Y, Avaygan H, Camacho N, Utine GE, Boduroglu K, Aktas D, Alikasifoglu M, Tuncbilek E, Orhan D, Bakar FT, Zabel B, Superti-Furga A, Bruckner-Tuderman L, Curry CJ, Pyott S, Byers PH, Eyre DR, Baldridge D, Lee B, Merrill AE, Davis EC, Cohn DH, Akarsu N, Krakow D (2010) Mutations in the gene encoding the RER protein FKBP65 cause autosomal-recessive osteogenesis imperfecta. Am J Hum Genet 87:551–559

    Article  Google Scholar 

  20. Kelley BP, Malfait F, Bonafe L, Baldridge D, Homan E, Symoens S, Willaert A, Elcioglu N, Van Maldergem L, Verellen-Dumoulin C, Gillerot Y, Napierala D, Krakow D, Beighton P, Superti-Furga A, De Paepe A, Lee B (2011) Mutations in FKBP10 cause recessive osteogenesis imperfecta and Bruck syndrome. J Bone Miner Res 26:666–672

    Article  PubMed  CAS  Google Scholar 

  21. Schwarze U, Cundy T, Pyott S, Christiansen H, Hegde MR, Bank R, Pals G, Ankala A, Connelly K, Seaver L, Yandow S, Raney H, Babovich-Vicsanovic D, Stoler J, Ben-Neriah Z, Segal R, Al-Aqeel A, Siderius L, Hannibal M, Hudgins L, McPherson E, Clemens M, Sussman MD, Steiner R, Mahan J, Smith R, Anyane-Yeboa K, Chong K, Uster T, Aftimos S, Sutton VR, Davis EC, Weis MA, Eyre D, Byers PH (2012) Mutation in FKBP10, which encodes a 65kD FK506 binding prolyl cis-trans isomerase, results in recessive forms of osteogenesis imperfecta and is the first Bruck syndrome (contractures and fractures) locus. Submitted for publication

  22. Van der Slot AJ, Zuurmond A-M, Bardoe AFJ, Wijmenga C, Pruijs HEH, Sillence DO, Brinckmann J, Abraham DJ, Black CM, Verzijl N, DeGroot J, Hanemaaijer R, TeKoppele JM, Huizinga TWJ, Bank RA (2003) Identification of PLOD2 as telopeptide lysyl hydroxylase, an important enzyme in fibrosis. J Biol Chem 278:40967–40972

    Article  PubMed  Google Scholar 

  23. Christiansen HE, Schwarze U, Pyott SM, AlSwaid A, Al Balwi M, Alrasheed S, Pepin MG, Weis MA, Eyre DR, Byers PH (2010) Homozygosity for a missense mutation in SERPINH1, which encodes the collagen chaperone protein HSP47, results in severe recessive osteogenesis imperfecta. Am J Hum Genet 86:389–398

    Article  PubMed  CAS  Google Scholar 

  24. Martinez-Glez V, Valencia M, Caparros-Martin JA, Aglan M, Temtamy S, Tenorio J, Pulido V, Lindert U, Rohrbach M, Eyre D, Giunta C, Lapunzina P, Ruiz-Perez VL (2012) Identification of a mutation causing deficient BMP1/mTLD proteolytic activity in autosomal recessive osteogenesis imperfecta. Hum Mutat 33:343–350

    Article  PubMed  CAS  Google Scholar 

  25. Becker J, Semler O, Gilissen C, Li Y, Bolz HJ, Giunta C, Bergmann C, Rohrbach M, Koerber F, Zimmermann K, de Vries P, Wirth B, Schoenau E, Wollnik B, Veltman JA, Hoischen A, Netzer C (2011) Exome sequencing identifies truncating mutations in human SERPINF1 in autosomal-recessive osteogenesis imperfecta. Am J Hum Genet 88:362–371

    Article  PubMed  CAS  Google Scholar 

  26. Homan EP, Rauch F, Grafe I, Lietman C, Doll JA, Dawson B, Bertin T, Napierala D, Morello R, Gibbs R, White L, Miki R, Cohn DH, Crawford S, Travers R, Glorieux FH, Lee B (2011) Mutations in SERPINF1 cause osteogenesis imperfecta type VI. J Bone Miner Res 26:2798–2803

    Article  PubMed  CAS  Google Scholar 

  27. Gong Y, Slee RB, Fukai N, Rawadi G, Roman–Roman S, Reginato AM, Wang H, Cundy T, Glorieux FH, Lev D, Zacharin M, Oexle K, Marcelino J, Suwairi W, Heeger S, Sabatakos G, Apte S, Adkins WN, Allgrove J, Arslan-Kirchner M, Batch JA, Beighton P, Black GC, Boles RG, Boon LM, Borrone C, Brunner HG, Carle GF, Dallapiccola B, De Paepe A, Floege B, Halfhide ML, Hall B, Hennekam RC, Hirose T, Jans A, Juppner H, Kim CA, Keppler-Noreuil K, Kohlschuetter A, Lacombe D, Lambert M, Lemyre E, Letteboer T, Peltonen L, Ramesar RS, Romanengo M, Somer H, Steichen-Gersdorf E, Steinmann B, Sullivan B, Superti-Furga A, Swoboda W, van den Boogaard MJ, Van Hul W, Vikkula M, Votruba M, Zabel B, Garcia T, Baron R, Olsen BR, Warman ML (2001) LDL receptor–related protein 5 (LRP5) affects bone accrual and eye development. Cell 107:513–523

    Article  PubMed  CAS  Google Scholar 

  28. Ai M, Heeger S, Bartels CF, Schelling DK, Osteoporosis-Pseudoglioma Collaborative Group (2005) Clinical and molecular findings in osteoporosis-pseudoglioma syndrome. Am J Hum Genet 77:741–753

    Article  PubMed  CAS  Google Scholar 

  29. Lapunzina P, Aglan M, Temtamy S, Caparros-Martin JA, Valencia M, Leton R, Martinez-Glez V, Elhossini R, Amr K, Vilaboa N, Ruiz-Perez VL (2010) Identification of a frameshift mutation in osterix in a patient with recessive osteogenesis imperfecta. Am J Hum Genet 87:110–114

    Article  PubMed  CAS  Google Scholar 

  30. Paterson CR, Ogston SA, Henry RM (1996) Life expectancy in osteogenesis imperfecta. BMJ 1996:312–351

    Google Scholar 

  31. Paterson CR, McAllion S, Stellman JL (1984) Osteogenesis imperfecta after the menopause. N Engl J Med 310:1694–1696

    Article  PubMed  CAS  Google Scholar 

  32. Paterson CR, Monk EA, McAllion SJ (2001) How common is hearing impairment in osteogenesis imperfecta? J Laryngol Otol 115:280–282

    Article  PubMed  CAS  Google Scholar 

  33. Bonita RE, Cohen IS, Berko BA (2010) Valvular heart disease in osteogenesis imperfecta: presentation of a case and review of the literature. Echocardiography 27:69–73

    Article  PubMed  Google Scholar 

  34. Adami S, Gatti D, Colapietro F, Fracassi E, Braga V, Rossini M, Tato L (2003) Intravenous neridronate in adults with osteogenesis imperfecta. J Bone Miner Res 18:126–130

    Article  PubMed  CAS  Google Scholar 

  35. Chevrel G, Schott A-M, 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 21:300–306

    Article  PubMed  CAS  Google Scholar 

  36. Bradbury LA, Barlow S, Geoghegan F, Hannon RA, Stuckey SL, Wass JAH, Russell RGG, Brown MA, Duncan EL (2012) Risedronate in adults with osteogenesis imperfecta type I: increased bone mineral density and decreased bone turnover, but high fracture rate persists. Osteoporos Int 23:285–294

    Article  PubMed  CAS  Google Scholar 

  37. Devogelaer JP, Malghem J, Maldague B, Nagant de Deuxchaines C (1987) Radiological manifestations of bisphosphonate treatment with APD in a child suffering from osteogenesis imperfecta. Skel Radiol 16:360–363

    Article  CAS  Google Scholar 

  38. Rauch F, Glorieux FH (2004) Osteogenesis imperfecta. Lancet 363:1377–1385

    Article  PubMed  CAS  Google Scholar 

  39. Gamsjaeger S, Buchinger B, Zwettler E, Recker R, Black D, Gasser JA, Eriksen EF, Klaushofer K, Paschalis EP (2011) Bone material properties in actively bone-forming trabeculae in postmenopausal women with osteoporosis after three years of treatment with once-yearly zoledronic acid. J Bone Miner Res 26:12–18

    Article  PubMed  CAS  Google Scholar 

  40. Roschger P, Fratzl-Zelman N, Misof BM, Glorieux FH, Klaushofer K, Rauch F (2008) Evidence that abnormal high bone mineralization in growing children with osteogenesis imperfecta is not associated with specific collagen mutations. Calcif Tissue Int 82:263–270

    Article  PubMed  CAS  Google Scholar 

  41. Land C, Rauch F, Glorieux FH (2006) Cyclical intravenous pamidronate treatment affects metaphyseal modeling in growing patients with osteogenesis imperfecta. J Bone Miner Res 21:374–379

    Article  PubMed  CAS  Google Scholar 

  42. Munns CF, Rauch F, Zeitlin L, Fassier F, Glorieux FH (2004) Delayed osteotomy but not fracture healing in pediatric osteogenesis imperfecta patients receiving pamidronate. J Bone Miner Res 19:1779–1786

    Article  PubMed  CAS  Google Scholar 

  43. 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 24:1282–1289

    Article  PubMed  CAS  Google Scholar 

  44. 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 Endocrinol Metab 96:355–364

    Article  PubMed  CAS  Google Scholar 

  45. 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 25:32–40

    Article  PubMed  CAS  Google Scholar 

  46. Antoniazzi F, Monti E, Venturi G, Franceschi R, Doro F, Gatti D, Zamboni G, Tato L (2010) Growth hormone in combination with bisphosphonate treatment in osteogenesis imperfecta. Eur J Endocrinol 163:479–487

    Article  PubMed  CAS  Google Scholar 

  47. Rauch F, Cornibert S, Cheung M, Glorieux FH (2007) Long-bone changes after pamidronate discontinuation in children and adolescents with osteogenesis imperfecta. Bone 40:821–827

    Article  PubMed  CAS  Google Scholar 

  48. Cheung MS, Glorieux FH, Rauch F (2009) Large osteoclasts in pediatric osteogenesis imperfecta patients receiving intravenous pamidronate. J Bone Miner Res 24:669–674

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgement

My sincere thanks go to Dr. Peter Byers, University of Washington, for his great help in preparing this article and for providing Fig. 2. The radiographs and the histology in Fig. 3 are reproduced with kind permission of Dr. Paul Hofman and Dr. Michael Dray, respectively.

Author information

Authors and Affiliations

  1. Department of Medicine, Faculty of Medical & Health Sciences, University of Auckland, Private Bag 92019, Auckland, New Zealand

    Tim Cundy

Authors
  1. Tim Cundy
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Tim Cundy.

Additional information

The author has stated that there is no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Cundy, T. Recent Advances in Osteogenesis Imperfecta. Calcif Tissue Int 90, 439–449 (2012). https://doi.org/10.1007/s00223-012-9588-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00223-012-9588-3

Keywords

Search

Navigation