Genetics of Osteogenesis Imperfecta Workup

  • Author: Horacio Plotkin, MD, FAAP; Chief Editor: Bruce Buehler, MD   more...
 
Updated: Mar 20, 2012
 

Laboratory Studies

  • Results from routine laboratory studies in patients with osteogenesis imperfecta (OI) are usually within reference ranges and they are useful in ruling out other metabolic bone diseases.
  • Collagen synthesis analysis is performed by culturing dermal fibroblasts obtained during skin biopsy. The occurrence of false-negative results is not clear, although the rate may be about 15%. Results are negative in syndromes resembling osteogenesis imperfecta.
  • Prenatal DNA mutation analysis can be performed in pregnancies with risk of osteogenesis imperfecta to analyze uncultured chorionic villus cells. Samples are obtained during chorionic villus sampling performed under ultrasonographic guidance when a mutation in another member of the family is already known.
  • Bone mineral density, as measured with dual-energy x-ray absorptiometry (DEXA), is low in children and adults with osteogenesis imperfecta despite the severity. Bone mineral densities can be normal in infants with osteogenesis imperfecta, even in severe cases. In pediatric patients, DEXA results are not useful for predicting the risk of fracture. No reliable published reference data regarding DEXA in infants is available.
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Imaging Studies

  • Obtain a radiographic skeletal survey after birth.
    • In mild (type I) osteogenesis imperfecta, images may reveal thinning of the long bones with thin cortices. Several wormian bones may be present. No deformity of long bones is observed.
    • In extremely severe (type II) osteogenesis imperfecta, the survey may reveal beaded ribs, broad bones, and numerous fractures with deformities of the long bones. Platyspondylia may also be revealed.
    • Moderate and severe (types III and IV) osteogenesis imperfecta, Imaging may reveal cystic metaphyses, or a popcorn appearance of the growth cartilage. Normal or broad bones are revealed early, with thin bones revealed later. Fractures may cause deformities of the long bones. Old rib fractures may be present. Vertebral fractures are common.
  • Prenatal ultrasonography can be used to detect limb-length abnormalities at 15-18 weeks' gestation.
    • Mild forms may result in normal sonogram findings.
    • Features include supervisualization of intracranial contents caused by decreased mineralization of calvaria (also calvarial compressibility), bowing of the long bones, decreased bone length (especially of the femur), and multiple rib fractures.
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Histologic Findings

  • The width of biopsy cores, the width of the cortex, and the volume of cancellous bone are decreased in all types of osteogenesis imperfecta. The number and thickness of trabeculae are reduced.
  • Samples may show evidence of defects in modeling of external bone in terms of the size and shape, the production of secondary trabeculae by endochondral ossification, and the thickening of secondary trabeculae by remodeling. Therefore, osteogenesis imperfecta might be regarded as a disease of the osteoblast.[9]
  • Bone formation is quantitatively decreased, but the quality of the bone material is probably most important in the pathogenesis of the disease.
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Contributor Information and Disclosures
Author

Horacio Plotkin, MD, FAAP  Adjunct Associate Professor of Pediatrics and Orthopedic Surgery, University of Nebraska School of Medicine

Horacio Plotkin, MD, FAAP is a member of the following medical societies: American Academy of Pediatrics and American Society of Human Genetics

Disclosure: Enobia Pharma Salary Management position

Chief Editor

Bruce Buehler, MD  Professor, Department of Pediatrics and Genetics, Director RSA, University of Nebraska Medical Center

Bruce Buehler, MD is a member of the following medical societies: American Academy for Cerebral Palsy and Developmental Medicine, American Academy of Pediatrics, American Association on Mental Retardation, American College of Medical Genetics, American College of Physician Executives, American Medical Association, and Nebraska Medical Association

Disclosure: Nothing to disclose.

Additional Contributors

Erawati V Bawle, MD, FAAP, FACMG Retired Professor, Department of Pediatrics, Wayne State University School of Medicine

Erawati V Bawle, MD, FAAP, FACMG is a member of the following medical societies: American College of Medical Genetics and American Society of Human Genetics

Disclosure: Nothing to disclose.

Alexander A Cacciarelli, MD, FACR Consulting Staff, Department of Radiology, St Joseph's Hospital and Medical Center of Phoenix

Disclosure: Nothing to disclose.

Mandar A Pattekar, MD, MS Consulting Staff, Department of Radiology, Methodist Hospital

Disclosure: Nothing to disclose.

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

References

  1. Plotkin H. Syndromes with congenital brittle bones. BioMed Central Pediatrics. 2004;4 (16):[Medline]. [Full Text].

  2. Morello R, Bertin TK, Chen Y, Hicks J, Tonachini L, Monticone M, et al. CRTAP is required for prolyl 3- hydroxylation and mutations cause recessive osteogenesis imperfecta. Cell. 2006;127:291-304. [Medline].

  3. Perez-Perez L, Allegue F, Alfonsin N, Caeiro JL, Fabeiro JM, Zulaica A. An uncommon association: elastosis perforans serpiginosa and osteogenesis imperfecta. J Eur Acad Dermatol Venereol. Feb 2009;23(2):172-4. [Medline].

  4. Hamamy HA, Teebi AS, Oudjhane K, Shegem NN, Ajlouni KM. Severe hypertelorism, midface prominence, prominent/simple ears, severe myopia, borderline intelligence, and bone fragility in two brothers: new syndrome?. Am J Med Genet A. Feb 1 2007;143(3):229-34. [Medline].

  5. Barnes AM, Carter EM, Cabral WA, et al. Lack of Cyclophilin B in Osteogenesis Imperfecta with Normal Collagen Folding. N Engl J Med. Jan 20 2010;[Medline].

  6. Choi JW, Sutor SL, Lindquist L, et al. Severe osteogenesis imperfecta in cyclophilin B-deficient mice. PLoS Genet. Dec 2009;5(12):e1000750. [Medline].

  7. Kamoun-Goldrat AS, Le Merrer MF. Animal models of osteogenesis imperfecta and related syndromes. J Bone Miner Metab. 2007;25(4):211-8. [Medline].

  8. Pillion JP, Shapiro J. Audiological findings in osteogenesis imperfecta. J Am Acad Audiol. Sep 2008;19(8):595-601. [Medline].

  9. Rauch F, Travers R, Parfitt AM, Glorieux FH. Static and dynamic bone hystomorphometry in children with osteogenesis imperfecta. Bone. 2000;26:581-9. [Medline].

  10. Rauch F, Munns C, Land C, Glorieux FH. Pamidronate in Children and Adolescents with Osteogenesis Imperfecta: Effect of Treatment Discontinuation. J Clin Endocrinol Metab. 2006;91:1268-74. [Medline].

  11. Castillo H, Samson-Fang L,. Effects of bisphosphonates in children with osteogenesis imperfecta: an AACPDM systematic review. Dev Med Child Neurol. Jan 2009;51(1):17-29. [Medline].

  12. Bargman R, Huang A, Boskey AL, Raggio C, Pleshko N. RANKL Inhibition Improves Bone Properties in a Mouse Model of Osteogenesis Imperfecta. Connect Tissue Res. Jan 6 2010;[Medline].

  13. Esposito P, Plotkin H. Surgical treatment of osteogenesis imperfecta: current concepts. Curr Opin Pediatr. Feb 2008;20(1):52-7. [Medline].

  14. [Guideline] Kellogg ND. Evaluation of suspected child physical abuse. Pediatrics. Jun 2007;119(6):1232-41. [Medline]. [Full Text].

  15. Plotkin H. Two questions about osteogenesis imperfecta. J Ped Orthop. 2006;26:148-149. [Medline].

  16. Plotkin H, Primorac D, Rowe D. Osteogenesis imperfecta. In: Glorieux F, Pettifor J, Juppner J, eds. Pediatric Bone: Biology and Disease. 2003:443-71.

  17. Plotkin, H. Syndromes with brittle bones, hyperostotic bone disease and fibrous dysplasia of bone. In: Lifshitz F, ed. Pediatric Endocrinology. 5th ed. 2006.

 
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Acute fractures are observed in the radius and ulna. Multiple fractures can be seen in the ribs. Old healing humeral fracture with callus formation is observed.
Beaded ribs. Multiple fractures are seen in the long bones of the upper extremities.
Wormian bones are present in the skull.
This newborn has bilateral femoral fractures.
 
 
 
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