Genetics of Osteogenesis Imperfecta Workup

Updated: Aug 02, 2021
  • Author: Eric T Rush, MD, FAAP; Chief Editor: Luis O Rohena, MD, PhD, FAAP, FACMG  more...
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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, such as hypophosphatasia or inherited forms of rickets.

Collagen synthesis analysis has historically been performed by culturing dermal fibroblasts obtained during skin biopsy. This testing modality has fallen out of favor, given that molecular diagnostic techniques are more accurate, have increased in availability, and have decreased in cost. Widespread adoption of next-generation sequencing (NGS) technology has allowed for parallel sequencing of many genes. Thus, there is little or no difference in cost or turnaround time for multigene panels compared with limiting investigation to the two procollagen I genes. 

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 radiographic absorptiometry (DRA), is generally low in children and adults with osteogenesis imperfecta. However, there is wide variation in the bone density of patients with OI. Still, normal bone density in a patient in whom osteogenesis imperfecta is being evaluated should prompt consideration of alternate diagnoses.


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.

  • In 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 or fracture of the long bones, decreased bone length (especially of the femur), and multiple rib fractures.


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. [52]

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