About OI

Osteogenesis Imperfecta (OI and sometimes known as Brittle Bone Disease, or “Lobstein syndrome”) is a genetic bone disorder. People with OI are born with defective connective tissue, or without the ability to make it, usually because of a deficiency of  Type-I collagen. A person is born with this disorder and is affected throughout his or her life time.

In addition to fractures, people with OI often have muscle weakness, hearing loss, fatigue, joint laxity, curved bones, scoliosis, blue sclerae, dentinogenesis imperfecta (brittle teeth), and short stature. Restrictive pulmonary disease occurs in more severely affected people.

Recent works suggest that OI must be understood as a multi-scale phenomenon, which involves mechanisms at the genetic, nano-, micro- and macro-level of tissues.

As a genetic disorder, OI is an autosomal dominant defect. Most people with OI receive it from a parent but it can be an individual (de novo or “sporadic”) mutation.


There are eight different types of OI, Type I being the most common, though the symptoms vary from person to person.

Type Description    
Type I mild  
Type II severe and usually lethal in the perinatal period    
Type III considered progressive and deforming  
Type IV deforming, but with normal scleras    
Type V shares the same clinical features of IV, but has unique histologic  findings (“mesh-like”)    
Type VI shares the same clinical features of IV, but has unique histologic findings (“fish scale”)    
Type VII associated with cartilage associated protein    
TypeVIII associated with the protein leprecan    

 Type I

Collagen is of normal quality but is produced in insufficient quantities:

  • Bones fracture easily
  • Slight spinal curvature
  • Loose joints
  • Poor muscle tone
  • Discoloration of the sclera (whites of the eyes), usually giving them a blue-gray color. The blue-gray color of the sclera is due to the underlying choroidal veins which show through. This is due to the sclera being thinner than normal because of the defective Type I Collagen not forming correctly.
  • Early loss of hearing in some children
  • Slight protrusion of the eyes

IA and IB are defined to be distinguished by the absence/presence of dentinogenesis imperfecta (characterized by opalescent teeth; absent in IA, present in IB). Life expectancy is slightly reduced compared to the general population due to the possibility of fatal bone fractures and complications related to OI Type I such as Basilar invagination.

Type II

Collagen is not of a sufficient quality or quantity

  • Most cases die within the first year of life due to respiratory failure or intracerebral hemorrhage
  • Severe respiratory problems due to underdeveloped lungs
  • Severe bone deformity and small stature

Type II can be further subclassified into groups A, B, C, which are distinguished by radiographic evaluation of the long bones and ribs. Type IIA demonstrates broad and short long bones with broad and beaded ribs. Type IIB demonstrates broad and short long bones with thin ribs that have little or no beading. Type IIC demonstrates thin and longer long bones with thin and beaded ribs.

 Type III

Collagen quantity is sufficient but is not of a high enough quality

  • Bones fracture easily, sometimes even before birth
  • Bone deformity, often severe
  • Respiratory problems possible
  • Short stature, spinal curvature and sometimes barrel-shaped rib cage
  • Loose joints
  • Poor muscle tone in arms and legs
  • Discolouration of the sclera (the ‘whites’ of the eyes)
  • Early loss of hearing possible

Type III is distinguished among the other classifications as being the “Progressive Deforming” type, wherein a neonate presents with mild symptoms at birth and develops the aforementioned symptoms throughout life. Lifespan may be normal, albeit with severe physical handicapping.

Type IV

Collagen quantity is sufficient but is not of a high enough quality

  • Bones fracture easily, especially before puberty
  • Short stature, spinal curvature and barrel-shaped rib cage
  • Bone deformity is mild to moderate
  • Early loss of hearing

Similar to Type I, Type IV can be further subclassified into types IVA and IVB characterized by absence (IVA) or presence (IVB) of dentinogenesis imperfecta.

 Type V

Same clinical features as Type IV. Distinguished histologically by “mesh-like” bone appearance. Further characterized by the “V Triad” consisting of a) radio-opaque band adjacent to growth plates, b) hypertrophic calluses at fracture sites, and c) calcification of the radioulnar interosseous membrane.

OI Type V leads to calcification of the membrane between the two forearm bones, making it difficult to turn the wrist. Another symptom is abnormally large amounts of repair tissue (hyperplasic callus) at the site of fractures. At the present time, the cause for Type V is unknown, though doctors have determined that it is inherited.

 Type VI

Same clinical features as Type IV. Distinguished histologically by “fish-scale” bone appearance.

 Type VII

In 2005 a recessive form called “Type VII” was discovered. Thus far it seems to be limited to a First Nations people in Quebec For more information see http://www.oif.org/site/DocServer/CRTAP.pdf?docID=4522.

Mutations in the gene CRTAP causes this type.


OI caused by mutation in the gene LEPRE1 is classified as type VIII.


At present there is no cure for OI. Treatment is aimed at increasing overall bone strength to prevent fracture and maintain mobility.

There have been many clinical trials performed with Fosamax (Alendronate), a drug used to treat women experiencing brittleness of bones due to osteoporosis. Higher levels of effectiveness apparently are to be seen in the pill form versus the IV form, but results seem inconclusive. The U.S. Food and Drug Administration (FDA) will not approve Fosamax as a treatment for OI because long term effects of the drug have not been studied, although it is often used in preteens, instead of Pamidronate.

Bone infections are treated as and when they occur with the appropriate antibiotics and antiseptics.


Physiotherapy used to strengthen muscles and improve motility in a gentle manner, while minimizing the risk of fracture. This often involves hydrotherapy and the use of support cushions to improve posture. Individuals are encouraged to change positions regularly throughout the day in order to balance the muscles which are being used and the bones which are under pressure.

Children often develop a fear of trying new ways of moving due to movement being associated with pain. This can make physiotherapy difficult to administer to young children.

Physical aids

With adaptive equipment such as crutches, wheelchairs, splints, grabbing arms, and/or modifications to the home many individuals with OI can obtain a significant degree of autonomy.


Bisphosphonates (BPs), particularly those containing nitrogen, are being increasingly administered to increase bone mass and reduce the incidence of fracture. BPs can be dosed orally (e.g. alendronate) or by intravenous injection/infusion (e.g. pamidronate, zoledronic acid).

BP therapy is being used increasingly for the treatment of OI. It has proven efficiency in reducing fracture rates in children, however only a trend towards decreased fracture was seen in a small randomized study in adults. While decreasing fracture rates, there is some concern that prolonged BP treatment may delay the healing of OI fractures, although this has not been conclusively demonstrated.

Pamidronate is used in USA, UK and Canada. Some hospitals, such as most Shriners, provide it to children. Some children are under a study of pamidronate. Pamidronate is usually administered as an intravenous infusion, lasting about three hours. The therapy is repeated every three to six months, and lasts for the life of the patient. Common side effects include bone pain, low calcium levels, nausea, and dizziness. According to recent results, extended periods of pamidronate, (i.e.;6 years) can actually weaken bones, so patients are recommended to get bone densities every 6 months-1 year, to monitor bone strength.


Metal rods can be surgically inserted in the long bones to improve strength, a procedure developed by Harold A. Sofield, MD, at Shriners Hospitals for Children in Chicago. During the late 1940’s, Sofield, Chief of Staff at Shriners Hospitals in Chicago, worked there with large numbers of children with OI and experimented with various methods to strengthen the bones in these children.[11] In 1959, with Edward A. Miller, MD, Sofield wrote a seminal article describing a solution that seemed radical at the time: the placement of stainless steel rods into the intramedullary canals of the long bones to stabilize and strengthen them. His treatment proved extremely useful in the rehabilitation and prevention of fractures; it was adopted throughout the world and still forms the basis for orthopedic treatment of OI.

Spinal fusion can be performed to correct scoliosis, although the inherent bone fragility makes this operation more complex in OI patients. Surgery for basilar impressions can be carried out if pressure being exerted on the spinal cord and brain stem is causing neurological problem.



1. Wikipedia
2. Osteogenesis Imperfecta Foundation Website