osteogenesis imperfecta

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.

Types

There are six types of OI, though the symptoms range from person to person. Type I is the most common and mildest form, followed by Type II, Type III and Type IV. Types V and VI have been more recently classified, and they share the same clinical features of IV, but each have unique histologic findings.

Type I

• Mendelian Inheritance in Man (OMIM) 166200 - Type IA
• Mendelian Inheritance in Man (OMIM) 166240 - Type IB

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

• Bones fracture easily, especially before puberty
• Slight spinal curvature
• Loose joints
• Poor muscle tone
• Discolouration of the sclera (whites of the eyes), usually giving them a blue-gray color
• Early loss of hearing in some children
• Slight protrusion of the eyes

IA and IB are distinguished by the absence/presence of dentinogenesis imperfecta (characterized by opalescent teeth.) (Absent in IA, present in IB.)

Type II

• Mendelian Inheritance in Man (OMIM) 166210 - 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

• Mendelian Inheritance in Man (OMIM) 259420 - 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 (whites of the eyes)
• Early loss of hearing, sometimes

Type III is distinguished amongst 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

• Mendelian Inheritance in Man (OMIM) 166220 - 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
• Discolouration of the sclera (whites of the eyes)
• 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

• Mendelian Inheritance in Man (OMIM) 166220 - 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 Drs. Francis Glorieux and 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 the 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

• No OMIM available. - Type VI

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

Treatment

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

Physiotherapy

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

Bisphosphonates (BPs), particularly the nitrogen-containing bisphosphonates, 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 (DiMeglio, 2006), however only a trend towards decreased fracture was seen in a small randomized study in adults (Chevrel, 2006). 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 an approved treatment for osteogenesis imperfecta in Canada, but not yet in the United States. Marketed under the brand name Aredia®, Pamidronate is usually administered as an intravenous infusion, lasting about 3 hours. The therapy is repeated every 3 to 6 months, and lasts for the life of the patient. Common side effects include bone pain, low calcium levels, nausea, and dizziness.

Surgery

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 - Chicago. During the late 1940’s, Sofield, Chief of Staff at Shriners Hospitals - Chicago, worked there with large numbers of children with OI and experimented with various method 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.

Bone infections

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

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.^[1]. An older system deemed less severe types "Osteogenesis Imperfecta Tarda" while more severe forms were deemed "Osteogenesis Imperfecta Congenita."^[2] 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 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.^[3]

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.^[4]. 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.

Portrayal in popular culture

Figures in film and television depicted as being afflicted with osteogenesis imperfecta include:

• The aptly-nicknamed Mr. Glass (so called because of the brittleness of his bones) is a major character in the movie Unbreakable. The character's real name is Elijah Price (played by Samuel L. Jackson).

• 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.

• An ER episode Point of Origin also had a subplot featuring an anonymous child with the condition.^[5]

• The fifth season of the series Scrubs also saw Elliot Reid doing research into the various types of therapy available to OI patients. ^[6]

• A member of the Burns family, featured in one episode of the reality TV show Extreme Makeover: Home Edition. They may have been selected, in part, due to the OIF.^[7]

• The 2005 movie Fragile features a child with this condition.