eMedicine Specialties > Orthopedic Surgery > Neoplasms

Osteogenesis Imperfecta: Differential Diagnoses & Workup

Author: Manoj Ramachandran, MBBS, MRCS, FRCS, Consultant Trauma and Orthopaedic Surgeon, Barts and the London NHS Trust; Honorary Senior Lecturer, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary's, University of London, UK
Coauthor(s): David H A Jones, MB, ChB, FRCS, FRCS Ed(Orth), Consultant Orthopedic Surgeon, Great Ormond Street Hospital for Children; Senior Clinical Lecturer, University College London Hospitals, UK; Pramod Achan, MBBS, FRCS(Orth), Senior Registrar, Royal National Orthopaedic Hospital, UK; Peter R Calder, MBBS, FRCS(Eng), FRCS (Tr&Orth), Consulting Surgeon, Department of Pediatric Orthopedic Surgery, The Royal National Orthopaedic Hospital, UK
Contributor Information and Disclosures

Updated: Nov 20, 2008

Differential Diagnoses

Other Problems to Be Considered

Because osteogenesis imperfecta can manifest itself in a wide variety of ways, differential diagnoses are best categorized into 3 stages of life: prenatal/neonatal, preschool/childhood, and adolescence/adulthood.

Prenatal/neonatal

The following skeletal dysplasias should be considered:

Thanatophoric dysplasia
Jeune dystrophy
Achondroplasia
Camptomelic dysplasia
Chondrodysplasia punctata
Chondroectodermal dysplasia (Ellis–van Creveld syndrome)
Nonaccidental injury
Menkes kinky-hair syndrome
Menkes Kinky Hair Disease

Hypophosphatasia may also be present. Patients may have blue sclerae, fractures, and wide fontanelles. This condition is characterized by low serum alkaline phosphatase levels and, in the severe recessive form, skin dimples overlying Bowdler spurs located symmetrically on the midshaft of the fibula, ulna, and radius.

Preschool/childhood

Genetic conditions to consider include the following:

Pyknodysostosis
Hajdu-Cheney syndrome
Osteopetrosis
Vitamin D–resistant rickets
Osteochondromatosis

Acquired conditions to consider include the following:

Secondary osteoporosis (immobilization)
Rickets
Scurvy
Leukemia
Cushing syndrome
Nonaccidental injury

Adolescence/adulthood

Conditions to consider in the adolescent and adult populations include the following:

Mafucci syndrome
Homocystinuria
Albright hereditary osteodystrophy
Wilson disease

For genetic conditions, patients present with fractures.

For idiopathic juvenile osteoporosis, patients aged 8-13 years present with skeletal pain, atraumatic fracture, and reduced bone density. The condition remits by early adulthood.

Workup

Laboratory Studies

  • An analysis of type I, III, and V collagens synthesized by fibroblasts may be helpful. Tests include sodium dodecyl sulfate–polyacrylamide gel electrophoresis (SDS-PAGE), 2-dimensional SDS-PAGE, cyanogen bromide (CNBr) mapping, and thermal stability studies.
  • An analysis of the amino acid composition of collagens may be useful.
  • DNA blood testing for gene defects has an accuracy of 60-94%.

Imaging Studies

  • Prenatal sonography is most useful in evaluating osteogenesis imperfecta types II and III. In its most severe form, the disease may be evident as early as 16 weeks' gestation.
  • Plain radiographs may depict 3 radiologic categories of osteogenesis imperfecta: category I, thin and gracile bones; category II, short and thick limbs; and category III, cystic changes. Radiologic features commonly seen include the following:
    • Fractures - Commonly transverse fractures and those affecting the lower limbs
    • Excessive callus formation and popcorn bones - Multiple scalloped, radiolucent areas with radiodense rims
    • Skull changes - Wormian bones, enlargement of frontal and mastoid sinuses, and platybasia with or without basilar impression
    • Deformities of the thoracic cage - Fractured and beaded ribs, pectus carinatum
    • Pelvic and proximal femoral changes - Narrow pelvis, compression fractures, protrusio acetabuli, and shepherd's crook deformities of the femurs
  • Dual x-ray absorptiometry (DEXA) may be used to assess low bone mineral density in children with milder forms of osteogenesis imperfecta.
  • CT densitometric bone scanning may be helpful in atypical cases of osteogenesis imperfecta, though normal bone density does not exclude mild forms of the disease.

Other Tests

  • Polarized light microscopy or microradiography may be used in combination with scanning electron microscopy to assess dentinogenesis imperfecta.
  • With skin biopsy, collagen can be isolated from cultured fibroblasts and assessed for defects, with an accuracy of 85-87%.12
  • Bone biopsy may show changes in the concentrations of noncollagenous bone proteins, such as osteonectin, sialoprotein, and decorin.

Procedures

Histologic Findings

See Pathophysiology, above.

Staging

No staging system is used for osteogenesis imperfecta.

More on Osteogenesis Imperfecta

Overview: Osteogenesis Imperfecta
Differential Diagnoses & Workup: Osteogenesis Imperfecta
Treatment & Medication: Osteogenesis Imperfecta
Follow-up: Osteogenesis Imperfecta
References
Further Reading
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References

  1. Smith R, Francis MJ, Houghton GR. The brittle bone syndrome. In: Osteogenesis Imperfecta. London: Butterworth. 1983.

  2. Brusin JH. Osteogenesis imperfecta. Radiol Technol. Jul-Aug 2008;79(6):535-48. [Medline].

  3. Cole WG. The Nicholas Andry Award-1996. The molecular pathology of osteogenesis imperfecta. Clin Orthop. Oct 1997;235-48. [Medline].

  4. Cole WG. Advances in osteogenesis imperfecta. Clin Orthop. Aug 2002;6-16. [Medline].

  5. Cole WG. Bone, cartilage and fibrous tissue disorders. In: Benson MKD, Fixsen JA, MacNicol MF, Parch K, eds. Children's Orthopaedics. 2002: 67-92.

  6. Baujat G, Lebre AS, Cormier-Daire V, Le Merrer M. [Osteogenesis imperfecta, diagnosis information (clinical and genetic classification)]. Arch Pediatr. Jun 2008;15(5):789-91. [Medline].

  7. Sillence D. Osteogenesis imperfecta: an expanding panorama of variants. Clin Orthop. Sep 1981;11-25. [Medline].

  8. Sillence DO, Senn A, Danks DM. Genetic heterogeneity in osteogenesis imperfecta. J Med Genet. Apr 1979;16(2):101-16. [Medline].

  9. Labuda M, Morissette J, Ward LM. Osteogenesis imperfecta type VII maps to the short arm of chromosome 3. Bone. Jul 2002;31(1):19-25. [Medline].

  10. Ward LM, Rauch F, Travers R. Osteogenesis imperfecta type VII: an autosomal recessive form of brittle bone disease. Bone. Jul 2002;31(1):12-8. [Medline].

  11. Duro Friedl EA, Ferrari Mayans L, Desalvo Portal LN, Ferrari Ruiz P, Bidondo Horno MP, Astraldi Tellechea MM. [Bruck syndrome: Osteogenesis imperfecta with congenital joint contractures.]. An Pediatr (Barc). Jul 2008;69(1):90-1. [Medline].

  12. Francis MJ, Smith R, Bauze RJ. Instability of polymeric skin collagen in osteogenesis imperfecta. Br Med J. Mar 9 1974;1(905):421-4. [Medline].

  13. Jones D, Hosalkar H, Jones S. The orthopaedic management of osteogenesis imperfecta. Clin Orthop. 2002;16:374-88.

  14. Zeitlin L, Fassier F, Glorieux FH. Modern approach to children with osteogenesis imperfecta. J Pediatr Orthop B. Mar 2003;12(2):77-87. [Medline].

  15. Forin V. [Paediatric osteogenesis imperfecta: medical and physical treatment]. Arch Pediatr. Jun 2008;15(5):792-3. [Medline].

  16. Sofield HA, Page MA, Mead NC. Multiple osteotomies and metal-rod fixation for osteogenesis imperfecta. J Bone Joint Surg. 1952;34A:500-2.

  17. Glorieux FH, Bishop NJ, Plotkin H, et al. Cyclic administration of pamidronate in children with severe osteogenesis imperfecta. N Engl J Med. Oct 1 1998;339(14):947-52. [Medline].

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Keywords

osteogenesis imperfecta, brittle bones, brittle bone disease, brittle-bone disease, blue sclera syndrome, blue-sclera syndrome, fragile bone disease, fragile-bone disease, Lobstein disease, Lobstein's disease, dentinogenesis imperfecta, Sillence classification, COL1A gene, COL2A gene, popcorn bones, osteoporosis-pseudoglioma, Bruck syndrome, Cole-Carpenter syndrome, OI, bone fragility, osteogenesis imperfecta congenita, osteogenesis imperfecta tarda, platyspondylia, platyspondylisis, broken bones

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Contributor Information and Disclosures

Author

Manoj Ramachandran, MBBS, MRCS, FRCS, Consultant Trauma and Orthopaedic Surgeon, Barts and the London NHS Trust; Honorary Senior Lecturer, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary's, University of London, UK
Manoj Ramachandran, MBBS, MRCS, FRCS is a member of the following medical societies: British Orthopaedic Association
Disclosure: Nothing to disclose.

Coauthor(s)

David H A Jones, MB, ChB, FRCS, FRCS Ed(Orth), Consultant Orthopedic Surgeon, Great Ormond Street Hospital for Children; Senior Clinical Lecturer, University College London Hospitals, UK
David H A Jones, MB, ChB, FRCS, FRCS Ed(Orth) is a member of the following medical societies: British Orthopaedic Association
Disclosure: Nothing to disclose.

Pramod Achan, MBBS, FRCS(Orth), Senior Registrar, Royal National Orthopaedic Hospital, UK
Disclosure: Nothing to disclose.

Peter R Calder, MBBS, FRCS(Eng), FRCS (Tr&Orth), Consulting Surgeon, Department of Pediatric Orthopedic Surgery, The Royal National Orthopaedic Hospital, UK
Peter R Calder, MBBS, FRCS(Eng), FRCS (Tr&Orth) is a member of the following medical societies: British Medical Association
Disclosure: Nothing to disclose.

Medical Editor

Miguel A Schmitz, MD, Consulting Surgeon, Department of Orthopedics, Klamath Orthopedic and Sports Medicine Clinic
Miguel A Schmitz, MD is a member of the following medical societies: American Academy of Orthopaedic Surgeons, American Orthopaedic Society for Sports Medicine, and Arthroscopy Association of North America
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

Ian D Dickey, MD, FRCSC, Adjunct Professor, Department of Chemical and Biological Engineering, University of Maine; Consulting Staff, Adult Reconstruction, Orthopedic Oncology, Department of Orthopedics, Eastern Maine Medical Center
Ian D Dickey, MD, FRCSC is a member of the following medical societies: American Academy of Orthopaedic Surgeons, British Columbia Medical Association, Canadian Medical Association, and Royal College of Physicians and Surgeons of Canada
Disclosure: Stryker Orthopaedics Consulting fee Consulting

CME Editor

Dinesh Patel, MD, FACS, Associate Clinical Professor of Orthopedic Surgery, Harvard Medical School; Chief of Arthroscopic Surgery, Department of Orthopedic Surgery, Massachusetts General Hospital
Dinesh Patel, MD, FACS is a member of the following medical societies: American Academy of Orthopaedic Surgeons, American Association of Physicians of Indian Origin, American College of International Physicians, and American College of Surgeons
Disclosure: Nothing to disclose.

Chief Editor

Harris Gellman, MD, Consulting Surgeon, Broward Hand Center; Voluntary Clinical Professor of Orthopedic Surgery and Plastic Surgery, Departments of Orthopedic Surgery and Surgery, University of Miami School of Medicine
Harris Gellman, MD is a member of the following medical societies: American Academy of Medical Acupuncture, American Academy of Orthopaedic Surgeons, American Orthopaedic Association, American Society for Surgery of the Hand, and Arkansas Medical Society
Disclosure: Nothing to disclose.

 
 
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