Crucial elements of the diagnostic work-up focus on the skeletal system. The physical exam includes measurements of length and head circumference, as well as notations on body proportions, including upper segment:lower segment ratio and arm span. In addition, the segmental lengths of each limb are measured to detect asymmetry. Individuals with OI frequently have relatively long arm span for length and a shortened lower segment (pubis to floor). Sclerae may be blue or blue-gray and teeth may have dentinogenesis imperfecta, with opalescent or yellow-brown enamel. In the thorax, the spine should be examined for scoliosis and the rib cage for flare and/or pectus carinatum or excavatum. In an infant, the size of the fontanelles should be noted. Also essential is a careful family pedigree, with inquiries about fractures, hearing loss, dentinogenesis imperfecta and adult height.
Radiographic examination consists of a selective skeletal survey. AP and lateral views of the long bones are examined for significant osteoporosis, bowing, healing fractures, metaphyseal flare and the sharpness of the growth plate. AP and lateral views of the spine are examined for scoliosis, vertebral compressions, and sharpness of the vertebral endplates. A lateral view of the skull should also be obtained to detect wormian bones.
It is essential to obtain a DEXA of the lumbar vertebral bodies for a relatively quantitative assessment of the individual’s osteoporosis. Since the bone matrix in types II, III, and IV OI is qualitatively abnormal, the DEXA z-score reflects the structural arrangement of the mineral as well as the quantity and therefore is not a straightforward quantitative measurement.
Differential diagnosis varies with the severity of OI and age of the patient. On prenatal ultrasound, severe OI may be confused with thanatophoric dysplasia, achondrogenesis type I, or campomelic dysplasia, all of which demonstrate relatively large heads and short limbs. Type III OI may need to be distinguished from infantile hypophosphatasia, which presents with severe osteoporosis and micromelia. Hypophosphatasia results in low serum alkaline phosphatase and increased inorganic pyrophosphate, while in OI, serum alkaline phosphatase is normal or increased. Type IV and more severe type I OI may be confused with primary juvenile osteoporosis or other secondary causes of osteoporosis in childhood, such as hypogonadism of malignancy. Some cases may require collagen studies or bone histology to make a definitive diagnosis. The major differential diagnosis with type I OI is child abuse. Collagen studies can complement decreased BMD and other skeletal features of OI, as necessary.
