Overview of Osteogenesis Imperfecta

The term Osteogenesis imperfecta was coined by Lobstein. The term is some what self explanatory! It is one of the relatively common bone dysplasias (1 in 20000 live births). OI involves all parts of the body that contain type 1 collagen to some extent giving rise to a variety of clinical presentations. Underlying mechanism in simple words is functional or actual decrease in collagen type 1 secondary to mutations in genes (most are inherited in autosomal dominant manner) coding for the same.

Clinical features include blue sclera, triangular facies, macrocephaly, hearing loss, dentition problems, chest deformity, scoliosis, limb deformities, fractures, joint laxity, constipation, sweating and growth retardation. There are several types, some being more severe than others (classified according to Sillence Classification). Type II has the most severe clinical presentation with most babies dying in newborn period. Type I is the mildest and commonest sub-type. There are more than 7 sub-types of OI. The commoner ones are described below.

Type		Teeth	Bone Fragility	Bone Deformity	Sclera	Spine	Skull	Prognosis
IA		Normal	Least severe	Moderate	Blue	20% Scoliosis and kyphosis	Wormian bones	Fair
IB		Dentinogenesis imperfecta	-	-	-	-	-	-
II		-	Very severe	Multiple fractures	Blue	NA	Wormian bones	Death in newborn period
III		Dentinogenesis imperfecta	Severe	Bowing of long bones	Blue at birth. Turns white gradually	Kyphoscoliosis	Hypoplastic wormian bones	Wheelchair-bound
IVA		Normal	Moderate	Moderate	White	Kyphoscoliosis	Hypoplastic wormian bones	Fair
IVB		Dentinogenesis imperfecta	NA	NA	NA	NA	NA	NA

Diagnosis of OI is usually made clinically and confirmed by genetic testing for mutations. Radiological tests are useful and confirmatory in many cases. Findings include: fractures, excessive callus formation and popcorn bones (multiple radiolucent areas with radiodense rims), wormian bones in the skull, enlargement of frontal and mastoid sinuses, deformities of ribs, narrow pelvis. In mild cases dual x-ray absorptiometry (DEXA) scan can be useful and will show decreased bone mineralization.

Treatment is essentially supportive. Bisphosphonates, especially pamidronic acid, are drugs that inhibit osteoclast-induced bone resorption. These are given in a cyclic manner (every few weeks) and have been shown to decrease the fracture rate (especially in type III and IV OI). Side effects of pamidronic acid include hypocalcemia (usually not severe), leukopenia, increase in bone pain (which is typically transient), and scleritis.

Other drugs with unclear roles in the treatment of OI include: Human growth hormone, teriparatide (which is human parathyroid hormone, brand name is Forteo). Bone marrow transplantation and gene therapy are being investigated. Aggressive physical therapy, occupational therapy and education of parents about injury prevention is essential.

Recommended further reading:
http://www.endotext.org/parathyroid/parathyroid17/index.html