Brittle bone disease or osteogenesis imperfecta (OI) is a rare heritable condition of connective tissue. It is characterized by brittle bones, fractures and extraskeletal manifestations. Both dominant and recessive patterns of inheritance are seen. The most common mutations affect the quantity and/or quality of type 1 collagen. The number of symptoms and the severity of symptoms of OI vary greatly among patients and range from mild forms with few exterior signs to very severe cases where life expectancy is decreased. Variable features of OI include short stature, hearing loss, scoliosis, dentinogenesis imperfecta, and cardiopulmonary issues. In addition, skin, blood vessels and internal organs may be fragile.
Prevalence and Prognosis
It is estimated that 6-7 per 100,000 people worldwide are affected. This translates to approximately 50,000 people in the United States. OI occurs equally in both males and females and in all races and ethnic groups. Treatment is directed at addressing clinical features and improving function. OI is a lifelong condition. Respiratory failure is the most frequent cause of death for people with OI, followed by accidental trauma. The most severe forms may cause death in infancy. With good medical management and supportive care, the majority of people who have OI will lead healthy, productive lives and can expect an average life span.
The majority of cases of OI (approximately 90%) are caused by dominant mutations in genes that encode for type 1 collagen. Other, mostly recessive, forms are caused by mutations that affect the collagen pathway. A few additional forms have been identified that do not have mutations related to type 1 collagen. Since the 1970s a list of numbered types has been used to describe the different forms of OI. A Type Chart and a description of Clinical Features by Type are included for your reference. OI can be inherited directly from an affected parent, or less commonly recessively from both parents. In some cases, parental mosaicism has been identified as an additional mechanism. Spontaneous dominant mutations may be responsible for 20-30% of new diagnoses. These new mutations do not appear to be caused by poor nutrition, drinking alcohol during pregnancy, exposure to toxins in the environment, nor are they caused by an action a parent should have taken. Mutations occur randomly in everyone.
OI exhibits wide variation in appearance and severity. Severity is described as mild, moderate, severe or lethal (causing early death). Clinical features vary not only between types but within types and even within families. At times, the distinction between types may not be clear. Children with milder OI may have few obvious clinical features. It is also important to recognize that some of the listed features are age dependent. Besides fractures, clinical features include:
- Bone deformity and bone pain
- Short stature
- Spine curves
- Low bone density
- Hearing loss (present in more than 50% of people with OI)
- Brittle teeth, dentinogenesis imperfecta or DI, (present in 50% of people who have OI)
- Respiratory problems including asthma; may be aggravated by chest wall deformity and/or spine deformity
- Vision problems including myopia and risk for retinal detachment; tinted sclerae (seen in 50% of patients)
- Loose joints, ligament laxity and muscle weakness
- Skin hyperlaxity; easy bruising
- Cardiac issues including mitral valve laxity
- Distinctive features of the skull include wormian bones (60%), late closing fontanels, and head circumference greater than average
General Health Issues
OI is a lifetime disorder and the general health care needs of children and adults who have OI are similar to those of people the same age in the general population.
- Typical childhood illnesses can be expected
- Immunizations are not contraindicated and protection from flu and pneumonia is suggested
- Information on reproductive health is necessary
- Obesity should be prevented and/or treated
- Illnesses seen in the general population including diabetes, heart disease and cancer occur
- Mental health issues including depression, anxiety and coping with social stigma occur
General Care Issues
- Higher baseline temperature is common; excessive perspiration may be observed
- Small, fragile blood vessels can lead to difficulty drawing blood or establishing an intravenous line
- When handling the patient support the spine and all limbs and do not pull or twist the torso or limbs
- Blood pressure measurements should not be taken on an arm that is fractured or bowed
- Patients often have anxiety about suffering a fracture from the cuff
- Pediatric size equipment may be necessary for small adults
- Manual cuffs are preferred to avoid and promptly relieve patient complaint about tightness
- Use automatic cuffs with care and consider using the neonatal setting
- Medication dose is usually based on the patient’s size, not age, in both children and adults
- Limit exposure to substances that reduce bone density such as corticosteroids
- Limit exposure to substances with side effects that lead to tendon rupture such as fluroquinolones.
Ben Amor IM, Glorieux FG, Rauch F. Genotype-Phenotype Correlations in Autosomal Dominant Osteogenesis Imperfecta. Journal of Osteoporosis 2011.
Bober, MB (Ed.). (2013). Introduction to Osteogenesis Imperfecta: A Guide for Medical Professionals, Individuals and Families Affected by OI. Gaithersburg, MD: Osteogenesis Imperfecta Foundation.
Shapiro J, Byers PH, Glorieux FG, Sponseller PD (Eds.). (2014). Osteogenesis Imperfecta: A Translational Approach to Brittle Bone Disease 1st Edition. New York, NY: Elsevier Academic Press.
Attribution This document was reviewed by Michael Bober, MD, PhD from Thomas Jefferson Medical College & A.I. duPont Hospital for Children. February 2015.