Osteogenesis imperfecta (OI), also referred to as brittle bone disease, is a rare, inherited bone disorder in which there is a disruption in the proteins that make strong bone architecture, making them “soft” or “brittle”. The name osteogenesis imperfecta translates to imperfect bone formation. Many symptoms of OI for each case vary from person to person but a common feature is bones that break easily. There are many types of OI depending on gene mutation and symptoms present, but most cases of OI are attributed to the disruption of a gene encoding for collagen I, the most abundant protein in the body. People with this disease are affected throughout this lifetime.
Types of osteogenesis imperfecta
Osteogenesis imperfecta presents itself through a wide range of appearances and severity. In the mildest form, there might not be any noticeable differences in appearance but in the most severe, it can require the person to be in a wheelchair and have a smaller statute. This range contributes to the many types of OI. The rare disease database reports on 21 types of OI. Due to the vast types of OI and the rarity of the disease, many of the types still require further research.
Different types of osteogenesis imperfecta are diagnosed based on the gene that causes OI and the type and severity of the symptoms. The most common, mildest OI is diagnosed as type I which is a change in the COL1A1 gene. The most severe type is type II, with a change in either the COL1A1 or COL1A2 gene.
A change in the gene that produces collagen I (COL1A1 or COL1A2) can produce two results. The first change of the gene causes the body to produce the correct formation of collagen but just in smaller amounts. This is often the effect in mild cases of OI.
Some of the more studied types include
is the mildest, most common form of osteogenesis imperfecta. Hopkins Medicine reports that approximately 50% of children with OI have type I.1
In this type of OI, there is normal collagen structure but less is produced than normal. There is only mild to no bone deformity. There are typically multiple bone fractures from childhood to puberty. This type can present itself with fractures from minimal trauma early in life or later when performing high-intensity activity. The frequency of fractures of someone with type I OI decrease following puberty.2
is the most severe type of OI, In many cases, it can cause death at birth or shortly after from an inability to breathe due to underdeveloped lungs. Oftentimes , multiple fractures happen before birth.
is the most severe type in babies who survive past being newborns. In this type, the baby might have shorter limbs than normal and bone fractures. Differences in appearance vary between different cases.
In this case, symptoms can range between type I and II. Fractures usually do not occur until crawling or walking but bones may be abnormally curved and growth can be affected.
Causes of osteogenesis imperfecta
Osteogenesis imperfecta is caused by a genetic mutation (change in a gene) that affects collagen production. While you may have heard of collagen in new health trends for your skin, collagen is found throughout the body and is an important component of bones and tissue. Collagen is the most abundant protein in the body, accounting for 30% of the total amount. It makes up connective tissue like ligaments and helps with the elasticity of tissue. However, in the bone, it accounts for more than 90% of the matrix that it is a part of. Collagen is important for the maintenance of the structure of the bone.4
We can compare collagen to building a house. The foundation of the house is the structure of the collagen. If we have less collagen production, our house won’t be as stable as someone with the average amount of collagen. This is what is often seen in mild cases. However, this is perceived to be better than a house that is built with an improper, poor-quality type of collagen. A house built with poor-quality collagen is weak and cannot withstand outside forces and can break easier, similar to bones. This is what we see in severe cases.
Genetic mutations are often passed from parent to child, however, approximately 25% of children with OI are born with no prior family history of OI.5 This could be due to a mutation that occurred during the development of the child.
Many other less-studied types of OI have been identified by a mutation of other genes that affect the extracellular matrix stability but more studies are needed.
Signs and symptoms of osteogenesis imperfecta
The symptoms of OI are dependent on the type of mutation that causes the OI.
A common symptom of osteogenesis imperfect is weak, brittle bones. Other factors are dependent on the type and severity of osteogenesis imperfecta.
Some symptoms are:6
- Malformation or bowing of long bones
- Bruises easily
- Weak muscles
- Triangular-shaped face
- Curved spine (scoliosis)
- Breathing problems
- Hearing loss
- Weak or loose joints
- Small stature
- Discolouration of the whites of the eye
Management and treatment for osteogenesis imperfecta
There is no cure for Osteogenesis imperfecta. Rather, treatment is focused on strengthing the body and preventing bone fractures.
If you are diagnosed with OI, your physician may recommend you to a physical therapist to focus on:
- Strengthening bone and muscle
- Nutrition, and overall physical well-being
A physical therapist will help you safely strengthen your muscles and increase weight-bearing capacity to help reduce the tendency for bones to fracture.2 A popular type of physical therapy for people with OI is hydrotherapy, which is strengthening the body in water. This is more gentle on the body and decreases the chance of fractures. It is important to consult your physician and physical therapist to determine the best course of action.
In severe cases, your doctor may recommend bisphosphonate therapy, a treatment that slows down the resorption of a broken bone while a new bone is forming. This therapy has been shown to increase bone strength but it cannot make the new bone normal. Another treatment is surgery for people with progressive deformity or repeated bone fractures to insert a metal rod into long bones such as the clavicle or femur.1
How is osteogenesis imperfecta diagnosed?
Osteogenesis Imperfecta is diagnosed through patient and family history of signs and symptoms. Genetic testing needs to be done to diagnose the type of genetic mutation that caused OI. Some diagnoses can be made before birth from symptoms presenting during the ultrasound.
Can osteogenesis imperfecta be prevented?
While it cannot be entirely prevented, treatments such as exercise, medication, and alignment surgery can increase bone strength and reduce the risk of fractures.
Who is at risk of osteogenesis imperfecta?
Individuals with a family history of OI and those with mutations in the collagen type 1 encoding genes are at risk of developing osteogenesis imperfecta.
How common is osteogenesis imperfecta?
When should I see a doctor?
If you or a family member exhibit symptoms of osteogenesis imperfecta or have a known family history of the condition, it's advisable to see a doctor for a proper evaluation and guidance on management.
Osteogenesis Imperfecta, also referred to as a brittle bone disease, is a rare genetic disorder characterised by fragile, soft bones that fracture easily. Most cases are diagnosed before or just after birth. In most cases, this disease is passed from parent to child due to a genetic mutation that affects the production of collagen I, an important protein for tissue and bone strength and structure. When this gene is affected, it can lead to decreased production of or poor-quality collagen I. In more severe cases, there may be curvature of bones, smaller stature, and a triangular-shaped face. There are often complications with breathing or hearing. Treatment focuses on strengthing the muscle and weight-bearing capabilities, with hydrotherapy being a popular choice for being more gentle.
- Osteogenesis Imperfecta [Internet]. 2022 [cited 2023 Mar 30]. Available from: https://www.hopkinsmedicine.org/health/conditions-and-diseases/osteogenesis-imperfecta
- Osteogenesis Imperfecta - Symptoms, Causes, Treatment | NORD [Internet]. [cited 2023 Mar 27]. Available from: https://rarediseases.org/rare-diseases/osteogenesis-imperfecta/
- Morello R. Osteogenesis Imperfecta and Therapeutics. Matrix Biol [Internet]. 2018 Oct [cited 2023 Mar 27];71–72:294–312. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6133774/
- Tzaphlidou M. Bone Architecture: Collagen Structure and Calcium/Phosphorus Maps. J Biol Phys Internet]. 2008 Apr [cited 2023 Mar 31];34(1–2):39–49. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2577747/
- BBS. About OI [Internet]. BBS. [cited 2023 Mar 26]. Available from: https://www.brittlebone.org/information-resources/about-oi/
- Branch NSC and O. Osteogenesis Imperfecta [Internet]. National Institute of Arthritis and Musculoskeletal and Skin Diseases. NIAMS; 2017 [cited 2023 Mar 29]. Available from: https://www.niams.nih.gov/health-topics/osteogenesis-imperfecta