osteogenesis imperfecta

Osteogenesis imperfecta (OI and sometimes known as Brittle Bone Disease) is a genetic bone disorder. People with OI are born without the proper protein (collagen), or the ability to make it, usually because of a deficiency of Type-I collagen. People with OI either have less collagen than normal or the quality is poorer than normal. As collagen is an important protein in bone structure, this impairment causes those with the condition to have weak or fragile bones.

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


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

Type Description Gene OMIM
Type I mild COL1A1, COL1A2 (IA), (IB)
Type II severe and usually lethal in the perinatal period COL1A1, COL1A2, CRTAP (IIA), (IIB)
Type III considered progressive and deforming COL1A1, COL1A2
Type IV deforming, but with normal scleras COL1A1, COL1A2
Type V shares the same clinical features of IV, but has unique histologic findings ("mesh-like") unknown
Type VI shares the same clinical features of IV, but has unique histologic findings ("fish scale") unknown
Type VII associated with cartilage associated protein CRTAP
Type VIII associated with the protein leprecan LEPRE1

Type I

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

  • Bones fracture easily
  • Slight spinal curvature
  • Loose joints
  • Poor muscle tone
  • Discolouration 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

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 radio-ulnar interosseous membrane.

  • As per Doctors Francis Glorieux, Frank Rauch, and Leanne Ward in the Shriners Hospital for Children in Quebec

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.

X-Ray OI Type V in Adult X-Ray OI Type V Kid

More on Type V Research More on OI Study

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.


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

There have been many clinical trials done with the drug, Fosamax, a drug used to treat women experiencing brittleness of bones due to osteoporosis. More success was seen in the pill form versus the IV form, but success was still seen. The 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, 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 both USA and Canada. Some hospitals, such as most Shriners, provide it to children. Also, some children are under a study of pamidronate. Marketed under the brand name Aredia, 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 pamidrinate, (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. In 1959, with Edward A. Millar, 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 also 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 problems.

History and alternative names

The condition, or types of it, have had various other names over the years and in different nations. Among some of the most common alternatives are Ekman-Lobstein syndrome, Vrolik syndrome, and the colloquial glass-bone disease. The name "Osteogenesis Imperfecta" dates to at least 1895 and has been the usual medical term in the twentieth century to present. The current four type system began with Sillence in 1979. An older system deemed less severe types "Osteogenesis Imperfecta Tarda" while more severe forms were deemed "Osteogenesis Imperfecta Congenita. As this did not differentiate well, and all forms are congenital, this has since fallen out of favour.

The condition has been found in an Ancient Egyptian mummy from 1000 BC. The Norse king Ivar the Boneless may have had this condition as well. The earliest studies of it began in 1788 with the Swede Olof Jakob Ekman. He described the condition in his doctoral thesis and mentioned cases of it going back to 1678. In 1831, Edmund Axmann described it in himself and two brothers. Johann Friedrich Georg Christian Martin Lobstein dealt with it in adults in 1833. Willem Vrolik did work on the condition in the 1850s. The idea that the adult and newborn forms were the same came in 1897 with Martin Benno Schmidt.

Variability of frequency in groups

Frequency is approximately the same across groups, but for unknown reasons the Shona and Ndebele of Zimbabwe seem to have a higher proportion of Type III to Type I than other groups.. However, a similar pattern was found in segments of the Nigerian and South African population. In these varied cases the total number of OIs of all four types was roughly the same as any other ethnicity.

Noted people with osteogenesis imperfecta

Historical figures whose OI status is disputed

Portrayal in popular culture

Figures in film and television depicted as having osteogenesis imperfecta include:

  • (1998) British actor and writer Firdaus Kanga, who wrote and starred in the 1998 BBC film Sixth Happiness partially based on his own life. The film deals with growing up in a 1970's cosmopolitan Bombay Parsi family with this condition. Kanga wrote Trying to Grow exploring the life of adolescents with this condition. Kanga also featured on Channel 4 documentaries 'Taboo' and 'Double the Trouble, Twice the Fun,' exploring religion, sexuality and disability.
  • (1999) The ER episode "Point of Origin" also had a subplot featuring an anonymous child with the condition.
  • (2000) The film Unbreakable features a character named Elijah Price (played by Samuel L. Jackson), who suffers from OI, and is nicknamed "Mr. Glass" due to the brittleness of his bones. In the film, the character gives an inaccurate description of OI classification types. He suggests that types of OI from I through IV get progressively worse and offers that "Type IV's don't last very long". However, the severity of OI classification types does not progress in numerical order, and Type IV patients generally have a normal life expectancy. Another inaccuracy in the film relates to the casting of Jackson in the role of Elijah Price. Jackson is over six feet tall, and it would be very unlikely for a person with OI to grow to that height.
  • (2001) Raymond Dufayel (sometimes simply called "the glass man" by his neighbors) in the French film Amélie; Dufayel is depicted as being confined to his house (the interior of which is heavily padded) by the condition.
  • (2004) A member of the Burns family, featured in one episode of the reality TV show Extreme Makeover: Home Edition, has the disease. They may have been selected, in part, due to the OIF.
  • (2004) Nabil Shaban presented a documentary about the Viking king Ivar the Boneless, who may have suffered the same condition as Shaban himself
  • (2005) The movie Fragile features a child with this condition.
  • (2006) The fifth season of the series Scrubs saw Elliot Reid doing research into the various types of therapy available to O.I. patients. Her obnoxious co-fellow Charlie then developed a new "gene therapy" cure, putting Elliot out of work.
  • (2006) The TV show Bones (TV series) found a body of a victim in a tub of lye. This occurred during season two, episode 5 "The Truth in the Lye." The main character, Dr. Temperance Brennan (A.K.A Bones), discovers the victim had O.I., probably type I or IV. The victim's children also had O.I.
  • (2007) Jeff "Joker" Moreau, pilot of the Systems Alliance spaceship, the SSV Normandy in the 2007 game Mass Effect, suffers from the condition which he calls by the informal name "Vrolik Syndrome" (see History and alternative names above). However, in the game, the condition only affects his leg bones.


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