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Osteogenesis Imperfecta Workup

  • Author: Manoj Ramachandran, MBBS, MRCS, FRCS; Chief Editor: Harris Gellman, MD  more...
Updated: Nov 24, 2014

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.

An analysis of type I, III, and V collagens synthesized by fibroblasts may be helpful. 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 OI.

Tests include the following:

  • Sodium dodecyl sulfate–polyacrylamide gel electrophoresis (SDS-PAGE)
  • Two-dimensional SDS-PAGE
  • Cyanogen bromide (CNBr) mapping
  • 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%. Prenatal DNA mutation analysis can be performed in pregnancies with risk of OI 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.



Prenatal ultrasonography is most useful in evaluating OI types II and III. It is capable of detecting limb-length abnormalities at 15-18 weeks’ gestation. In its most severe form, the disease may be evident as early as 16 weeks’ gestation.

Mild forms of OI may result in normal findings on ultrasonography. 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.


Plain Radiography

Obtain a radiographic skeletal survey after birth. Plain radiographs may depict the following three radiologic categories of OI:

  • Category I – Thin and gracile bones
  • Category II – Short and thick limbs
  • Category III – Cystic changes

Radiologic features commonly seen include the following:

  • Fractures – Commonly, transverse fractures and those affecting the lower limbs (see the first image below)
  • Excessive callus formation and popcorn bones - Multiple scalloped, radiolucent areas with radiodense rims
  • Skull changes - Wormian bones (see the second image below), enlargement of frontal and mastoid sinuses, and platybasia with or without basilar impression
  • Deformities of the thoracic cage - Fractured and beaded ribs (see the third and fourth images below) and pectus carinatum
  • Pelvic and proximal femoral changes - Narrow pelvis, compression fractures, protrusio acetabuli, [15] and shepherd’s-crook deformities of the femurs
    Newborn has bilateral femoral fractures. Newborn has bilateral femoral fractures.
    Wormian bones are present in skull. Wormian bones are present in skull.
    Acute fractures are observed in radius and ulna. M Acute fractures are observed in radius and ulna. Multiple fractures can be seen in ribs. Old healing humeral fracture with callus formation is observed.
    Beaded ribs. Multiple fractures are seen in long b Beaded ribs. Multiple fractures are seen in long bones of upper extremities.

In mild OI (type I), 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 OI (type II), the survey may reveal beaded ribs, broad bones, and numerous fractures with deformities of the long bones. Platyspondylia may also be revealed.

In moderate and severe OI (types III and IV), 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.



Dual x-ray absorptiometry (DEXA) may be used to assess bone mineral density in children with milder forms of OI. Bone mineral density, as measured with DEXA, is low in children and adults with OI regardless of severity. Bone mineral densities can be normal in infants with OI, 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 are available.

Densitometric bone scanning with computed tomography (CT) may be helpful in atypical cases of OI, 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%.[16]

Bone biopsy may show changes in the concentrations of noncollagenous bone proteins, such as osteonectin, sialoprotein, and decorin.


Histologic Findings

The width of biopsy cores, the width of the cortex, and the volume of cancellous bone are decreased in all types of OI. 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, OI might be regarded as a disease of the osteoblast.[17]

Bone formation is quantitatively decreased, but the quality of the bone material is probably most important in the pathogenesis of the disease.

Contributor Information and Disclosures

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.


Pramond Achan, MBBS, FRCS Senior Registrar, Royal National Orthopaedic Hospital, UK

Disclosure: Nothing to disclose.

David H A Jones, MBChB, 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, MBChB, FRCS is a member of the following medical societies: British Orthopaedic Association

Disclosure: Nothing to disclose.

Vinod K Panchbhavi, MD, FACS Professor of Orthopedic Surgery, Chief, Division of Foot and Ankle Surgery, Director, Foot and Ankle Fellowship Program, Department of Orthopedics, University of Texas Medical Branch School of Medicine

Vinod K Panchbhavi, MD, FACS is a member of the following medical societies: American Academy of Orthopaedic Surgeons, American College of Surgeons, American Orthopaedic Association, American Orthopaedic Foot and Ankle Society, Orthopaedic Trauma Association, Texas Orthopaedic Association

Disclosure: Serve(d) as a speaker or a member of a speakers bureau for: Styker.

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, Leonard M Miller School of Medicine, Clinical Professor, Surgery, Nova Southeastern 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, Arkansas Medical Society

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.

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; Cadence Honoraria Speaking and teaching

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

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Acute fractures are observed in radius and ulna. Multiple fractures can be seen in ribs. Old healing humeral fracture with callus formation is observed.
Beaded ribs. Multiple fractures are seen in long bones of upper extremities.
Wormian bones are present in skull.
Newborn has bilateral femoral fractures.
Table 1. Adapted Sillence Classification of Osteogenesis Imperfecta
Type Genetic Teeth Bone Fragility Bone Deformity Sclera Spine Skull Prognosis
IA AD* Normal Variable but less severe than other types Moderate Blue 20% scoliosis and kyphosis Wormian bones Fair
IB AD Dentinogenesis imperfecta NA NA NA NA NA NA
II AD Unknown Very severe Multiple fractures Blue NA Wormian bones with absence of ossification Perinatal death
III AD Dentinogenesis imperfecta Severe Progressive bowing of long bones and spine Bluish at birth but white in adults Kyphoscoliosis Hypoplastic wormian bones Wheelchair-bound, not ambulatory
IVA AD Normal Moderate Moderate White Kyphoscoliosis Hypoplastic wormian bones Fair
IVB AD Dentinogenesis imperfecta NA NA NA NA NA NA
* AD = autosomal dominant; NA = not applicable.
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