Osteogenesis Imperfecta (Brittle Bone Disease)

Brittle bone disease (osteogenesis imperfecta) is inherited from a parent.

Osteogenesis imperfecta (OI) refers to a group of bone diseases with a common defect in bone formation. There are at least 8 known types of osteogenesis imperfecta that range in severity, but people with all kinds of conditions have bones that tend to break easily, also referred to as brittle bones. Brittle bone disease is estimated to affect 6 or 7 out of every 100,000 people worldwide.

Other names for osteogenesis imperfecta include:

• Brittle bone disease
• Glass bone disease
• Fragile bone disease
• Ekman-Lobstein Disease
• Lobstein Disease (Type I)
• Vrolik Disease (Type II)

Temporary brittle bone disease is not the same thing as osteogenesis imperfecta. It is a term that has been used to describe frequent fractures occurring during the first year of life, although a definite cause of the condition has not been identified.

The term "temporary brittle bone disease" is controversial because many fractures that cannot otherwise be accounted for have been suggested as forms of deliberate injury, and some experts have argued that temporary brittle bone disease does not exist. Other experts argue that nutritional deficiencies, metabolic conditions, or other temporary conditions can render bones susceptible to fracture in the first year since these fractures often occur in the absence of other signs of deliberate injury such as bruising.

No, osteoporosis is the loss of bone density in normal bones. In brittle bone disease, there is a genetic defect that causes bones to be formed abnormally. However, in both conditions, there is a greater likelihood of bone fracture.

Osteogenesis imperfecta is divided into eight types designated by the Roman numerals I through VIII. The type of disease of the bone is determined by the particular genetic mutation and pattern of inheritance.

• Type I is the mildest and most common form of the disease and makes up about half of all cases.
• Type II is the most severe form. Infants with Type II brittle bone disease develop fractures even inutero and have severe abnormalities at birth. Death usually occurs within a few weeks of birth.
• Type III is the most severe form among infants who survive the neonatal period. These infants develop multiple fractures and have short stature and other abnormalities.
• Type IV and V brittle bone disease can vary in severity from mild to more severe.
• Type VI is very rare and is similar to types IV and V.
• Types VII and VIII are usually inherited in an autosomal recessive pattern (meaning that a defective gene must be received from each parent).

Brittle bone disease is caused by genetic defects or mutations. These mutations can either be inherited from the parents or may arise on their own as new mutations.

Most cases of brittle bone disease are inherited from the parents (congenital) in an autosomal dominant manner, meaning that only one copy of the defective gene is necessary (from one parent) for the condition to be present. However, some forms of the condition may be inherited in an autosomal recessive pattern, meaning that two copies of a defective gene are required (one from each parent). Mutations in the COL1A1, COL1A2, CRTAP, and P3H1 genes cause osteogenesis imperfecta. These genes code for proteins that are important for collagen formation. Collagen is an important component of bones and other body structures.

Brittle bone disease manifests in childhood. In the most severe forms, changes can even be identified in the fetus in utero.

Symptoms and signs of brittle bone disease vary according to the type, but may include:

• Frequent fractures that lead to skeletal deformity
• Short stature
• Bluish coloration to the whites of the eyes (sclerae)
• Hearing loss
• Low birth weight and birth defects in certain forms
• Problems with tooth and jaw development
• Lung defects in some newborns

The defective brittle bones themselves are not painful, but chronic pain may develop in some people with osteogenesis imperfecta due to repeated fractures and skeletal changes. Pain may also result from acute injuries such as fractures.

The characteristic symptoms of brittle bone disease typically suggest the diagnosis. The diagnosis is confirmed by blood and urine tests to rule out other conditions and by family history and genetic testing.

Osteogenesis imperfecta cannot be cured, and treatment is directed at managing symptoms and quality of life. Treatment goals include minimizing fractures and promoting general health and function. The treatment team may include primary care physicians, geneticists, rehabilitation specialists, endocrinologists, neurologists, orthopedic specialists, and pulmonologists.

Treatments can include surgical procedures to repair fractures or correct deformities. Medications such as bisphosphonates (approved for osteoporosis) are sometimes used to improve bone density. Mobility aids including walkers, crutches, and wheelchairs, may be used when needed.

Brittle bone disease has no cure.

The prognosis for infants with the most severe form of osteogenesis imperfecta is poor, and most children may not live beyond a few weeks. The prognosis for those with milder forms of the condition who receive good medical management is much better, and many people may have average lifespans.