An overview

Osteogenesis imperfecta is also known as brittle bone disease. It is a disorder characterized by the increased fragility of bones resulting in easy breakage. Usually, it presents itself at birth, but develops mostly in children whose family has a history of the disease.
Osteogenesis imperfecta, known informally as OI also means “imperfectly-formed bones.”
Osteogenesis imperfecta may be mild or severe. Most cases reported in the hospital are the mild type – they result in very few fractures. The severe forms of the disorder may cause:
• Cardiac failure
• Problems with the spinal cord
• Loss of hearing
• Deformities which may last a lifetime.
In some cases, the disorder can be life-threatening, especially if it occurs in infants before birth or shortly after birth. Research has shown that at least one in 20,000 persons will develop the disorder. Osteogenesis imperfecta is not gender specific meaning that it occurs equally in both males and females and in ethnic groups.
The underlying cause of the disorder is an issue with the connective tissue due to a conspicuous absence of Type 1 collagen. The major cause of this is a mutation in the COL1A2 or the COL1A1 genes. The disorder is inherited in an autosomal dominant fashion or through a new mutation. Osteogenesis imperfecta is of eight types with the first being the least severe and type II being the most severe. Diagnosis of the disorder is dependent on the symptoms and is often confirmed by DNA or collagen testing.
This disorder does not have a cure, at least for the mean time. Fractures can be prevented by maintaining a healthy lifestyle and taking care not to smoke or use any tobacco products. Treatment involves analgesics, physical therapy, wheel chairs or braces and in extreme cases, surgery. Sometimes, surgical insertion of metal rods through the long bones may be done to support the bones. Research has shown that the use of biphosphate medications may be of help.
The prognosis depends on the type. Many patients however have good prognosis. This may not be unconnected with the advances in medical science and technology. Note that the term osteogenesis imperfecta was used formally from 1895.


Osteogenesis imperfecta or brittle bone disease is classified into eight – the reason being that four different genes are responsible for the production of collagen. Some of these genes or all of it may be affected in people suffering from the disorder. The defective genes allow the development of eight types of osteogenesis imperfecta identified as 1 OI through 8 OI. The most common types are the first four while the last four are extremely rare. In fact, most are subtypes of the 4 OI class. Below, we will outline the four most common types of osteogenesis imperfecta.
Type 1 Osteogenesis Imperfecta: This is the least serious and most common form of the disorder. Here, the body produces collagen of high quality but inadequate amounts. The result of this is the formation of fragile bones. Children with this type of OI usually have mild fractures and trauma. However, the fractures are not common in adults. The teeth may also be affected leading to cracks in the dentition and the cavities.
Type 2 Osteogenesis Imperfecta: This is the most severe form of the disorder. It may be fatal (life-threatening). Here, the body either produces inadequate collagen, or collagen of very poor quality. It may cause deformities in the bone. Children born with this disorder may have misshapen or broken ribs, narrowed chest or poorly developed lungs. Babies having this disorder may die before birth or shortly after birth.
Type 3 Osteogenesis Imperfecta: This is another severe form of the disorder. It causes easy breakage of bones. In type 3 Osteogenesis Imperfecta, the child produces adequate amount of collagen, but it is of poor quality. The bones may even break prior to birth. Bone deformities are common and may worsen as the child ages.
Type 4 Osteogenesis Imperfecta: This is the most variable form of the disorder – the reason being that the symptoms vary. As with the Type 3, the body produces adequate amounts of collagen, but the quality is poor. Children with this disorder usually have bowed legs, though the bowing decreases with age.


People with Osteogenesis Imperfecta usually have a defective connective tissue, or they may be born without the ability to make the connective tissues, probably due to a deficiency of Type – 1 collagen. The deficiency stems from a substitution of the amino acid glycine to more heavy amino acids in the collagen triple X structure. Amino acid side chains with a larger structure forms a stearic hindrance that causes the collagen complex to bulge. The in turn influences the inter-molecular interactions and molecular nano-mechanics. The body responds to this by hydrolyzing the altered collagen structure. If the body does not destroy the poorly formed structure, the relationship between the hydroxyapatite crystals and the collagen crystals to form the bones may be altered, resulting in brittleness of the bones.
Another mechanism giving rise to complications is that the stress state within altered collagen fibrils is altered at the location of mutations, where locally larger shear forces lead to failure of fibrils even at moderate loads as the homogenous stress state found in healthy collagen fibrils is lost.
Genetically, osteogenesis imperfecta is seen as an autosomal dominant disorder of the Type 1 collagen. Many cases occur as a result of mutation in the COL1A1 and COL1A2 genes. Over the years, autosomal recessive forms have been identified. Many cases are due to receipt of the defective gene from a parent. 35 percent of cases are however due to de novo mutations.

Symptom of the disorder
Symptoms vary according to the type of disease. Fragility of bones is common in all cases. However, there is a variation in the severity from person to person. Osteogenesis imperfecta has one or more of the following symptoms:
• Deformities of the bones
• Multiple broken bones
• Weakening of the teeth
• Loose joints
• The sclera has a characteristic blue color
• Arms and legs get bowed
• The spine assumes an abnormal lateral curvature
• Deafness at an early age
• Cardiovascular defects
• Disorders of the respiratory system.



The basis for diagnosis is medical imaging and symptoms. Medical imaging includes plain X-rays. Via medical imaging, abnormalities may be observed in the spine and all extremities. Confirmation of the diagnosis may be done through collagen or DNA testing. However, in many cases, fracture without significant trauma or a blue sclera and other clinical features are more than enough for a diagnosis.
A skin biopsy may be conducted to determine the quantity and the quality of type 1 collagen. Diagnosis can be confirmed via the DNA testing. However, it cannot excluded because not all mutations that cause osteogenesis imperfecta are tested for. Usually, ultrasound is used for the diagnosis of Osteogenesis Imperfecta Type II during pregnancy. This helps in identifying other fractures in the fetus. Osteogenesis imperfecta cortical bone shows a high level of porosity, connectivity and canal diameter in micro-computed tomography.


Treatment for osteogenesis imperfecta

Osteogenesis Imperfecta has no cure. However, there are therapies that may support the patient, or help minimize the risk of broken bones and raise the patient’s quality of life. Treatments that may be adopted include:
• Occupational and physical therapy to increase the child’s muscle strength and mobility.
• Use of biphosphate medications to strengthen the bones
• Analgesics in the event of pain
• Less strenuous exercise to assist in bone build up
• Surgical insertion of rods in the child’s bones
• Correction of bone deformities via reconstructive surgery


Research has shown that in the United States, at least one in every 20,000 live births have the disorder. At least 20,000 to 50,000 people in the United States are affected by the disorder. The Ndebele and Shone tribes of Zimbabwe have a higher frequency of Type III to Type I than others. Similar scenarios exists in the South African and Nigerian populations.



Prognosis varies depending on the type. Children with Type 1 OI may live a normal life with not many problems.
Type 2 OI is fatal. Children affected may die before birth or shortly after being delivered, mostly due to issues with the respiratory system.
Type 3 OI are worse. Their bones are deformed and movement is only possible with the aid of a wheel chair. Their lifespans are shorter compared to patients with Type 1 or 4.
The life expectancy of Type 4 OI patients is normal. However, they may need the aid of crushes to walk around.



William B (2006). Andrew’s Diseases of the Skin: Clinical Dermatology (10th ed.). Saunders. P. 517. ISBN 978-0721629216
Osteogenesis Imperfecta. rarediseases.info.nih.gov. Retrieved 2018-04-17
Grond-Ginsbach C, Debette S, Pezzini A (2005). “Genetic approaches in the study of risk factors for cervical artery dissection.” Frontiers of Neurology and Neuroscience. 20: 30-43.

Leave a Reply

Your email address will not be published. Required fields are marked *