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Brittle bones / OI

About Brittle bones / OI

Group of metabolic bone disease where the collagen content of bone is either reduced, absent or of poor quality.

The different types of OI conditions seen are due to the genetic defect in the gene for Collagen I. Over 90 % of cases are due to mutation of the genes for Type I collagen. This Type I collagen has two α1 chains and one α2 chain forming a trihelix. These chains are coded by COL 1A1 gene and COL 1A2 genes respectively. In the mild form (OI IA) the mutations reduce the amount of collagen available in tissues but in other forms a mutant collagen is deposited in the tissues.

Less than 10% of OI cases are due to recessive mutations in genes that control the collagen pathway. Children with OI type V and Type VI do not show mutation in Collagen type I gene. Several new genetic mutations have been described in the causation of OI.

Types of OI

Although several OI types have been described, the classification proposed by Dr David Sillence is still valid. New types have been added with better understanding of the disease mechanism.

Type I

OI type I is the most benign form and manifests with few fractures, and minimal limb deformities. Some of these children present with elbow and shoulder dislocations. These children have blue sclera and the incidence of fracture decreases with age.

Type II

This is the most severe form for OI and can lead to perinatal death in some children. The ones that survive have severe deformity and multiple fractures. There is macrocephaly, poor cardio-respiratory function, dark blue sclera. Radiographs show poor mineralization of skull, flattened vertebral bodies and short and broad femur. This may occur due to dominant mutation in type I Collagen or Parental Mosaicism.

Type III

Also a severe form of OI where the quality of type I collagen is poor leading to frequent fractures and deformities. Triangular facies,macrocephaly, short stature, spinal deformity and poor muscle strength is common. The sclera may not be affected, but teeth are commonly involved.

Type IV

This type lies between Type I and III. The fracture rate is less, although bowing deformity is common with short femur and humerus. The height is also affected. The sclera have a blue tint which improves with age. Dentinogenesis imperfecta may be present or absent.

Type V

This behaves like Type IV but the distinguishing feature is the hyperplastic callus in long bones or after osteotomy. Calcification of the interrosseous membrane of the forearm may restrict forearm rotation and cause radial head dislocation. This does not involve deficit in Type I collagen.

Type VI

Very rare and behaves as Type IV but the unique feature is the poor mineralization of bone. Can be diagnosed with Bone Biopsy.

Two recessive types have been identified due to post-translation modification.


These two are recessive types of OI seen in about 10% children and are caused by specific gene mutation other than Type I Collagen.

The affected children can have moderate to severe OI . Type VII is caused by mutation in the Cartilage-associated protein gene (CRTAP) and can resemble type II or IV OI.

All affected children have short stature, coxa vara, rhizomelic type shortening of bones.


Children have severe growth deficiency and undermineralization of skeleton. This is due to deficiency in the LEPRE gene. This affects the post-translational modification of collagen.

Summary of Common 4 Types of OI

Sillence Types
Types Features Inheritance
I (Classical form)
Joint laxity, wormain bones.
I A: normal dentition
I B: abnormal dentition
Grey-blue sclerae, osteopenia, AD
II (Lethal perinatal)
Dwarfism, blue sclera, severe AD
III ( Progressive)
deformation of bones, poor
White sclera, thin progressive AD/AR
IV A: Normal teeth
IV B: Abnormal teeth
White sclera, moderate osteopenia, AD

Diagnosis of Brittle bones

The clinical diagnosis is often made with incidental finding of facture in a toddler or infant with trivial injury.

A simple twist of the leg, or a mild fall which otherwise would not lead to a fracture, will cause the bone to break in a child with OI.

Some children present with multiple fractures in different stages of healing and this is attributed to poor bone strength or poor calcium intake, whereas the diagnoses here is a clincher.

The other key clinical features of brittle bone disease include grey-blue sclera, dentinogenesis imperfecta, joint laxity and premature hearing loss.

The bluish discolouration of sclera is highly variable. It is also normally seen in children less than 18 months of age. Thus persistence of blue sclerae after age two usually indicate OI.

Dentinogenesis imperfecta or abnormal translucent , fragile teeth are seen in some children.

Children may also present with long bone deformities, and spinal or chest wall deformities in the growing years.

Some children also have skin and soft tissue laxity, poor muscle tone, flat feet and delay in motor milestones.

A triangular facies, short trunk and barrel shaped chest may be seen with severe OI.

Many times the diagnosis is delayed as treating physician fails to elicit proper history.

We have seen many children where the diagnosis has not been made despite repeated fractures. This can lead to muscle wasting, poor mobility and functional limitations in the active years of childhood life.

Imaging of Brittle bones:


Plain X-rays reveal osteopenia, and thinning of cortex. The skull is typically enlarged and in 60 % of cases Wormian bones are seen.

In an event of fracture, the bone may show transverse or oblique fracture lines with bone displacement, various stages of callus formation and deformity in chronic fractures.

DEXA Scanning is now recommended to see the bone density and also to monitor the medical therapy with bisphosphonates.


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