Osteogenesis Imperfecta: A Complete Guide to Symptoms, Types, and Management

What Is Osteogenesis Imperfecta?

Osteogenesis imperfecta (OI) is a rare genetic connective tissue disorder that primarily affects the bones, making them fragile and prone to fractures. The underlying defect usually involves abnormal production or structure of type I collagen, a crucial protein that provides strength and structure to bone and connective tissue.

Osteogenesis imperfecta, or brittle bone disease, affects individuals differently, ranging in severity from mild forms with few fractures to severe forms causing frequent fractures, skeletal deformities, and growth problems. In addition to bone fragility, OI can impact other tissues, leading to issues such as hearing loss, dental problems, and joint laxity.

Key Symptoms of Osteogenesis Imperfecta

• Fragile bones that break easily, often with minimal trauma
• Frequent bone fractures over a lifetime, sometimes beginning before birth
• Short stature or slow growth
• Bone deformities (curved or misshapen bones, bowed legs, scoliosis)
• Loose or hypermobile joints (joint laxity)
• Blue, grey, or purplish tint to the sclerae (the whites of the eyes)
• Hearing loss, which may develop in childhood or adulthood
• Dental problems (brittle teeth, weak enamel, dentinogenesis imperfecta)
• Respiratory issues (lung problems, barrel-shaped chest)
• Easy bruising and delayed wound healing
• Triangular-shaped face
• Macrocephaly (enlarged head) and, in rare cases, hydrocephalus (fluid accumulation in the brain)

Types of Osteogenesis Imperfecta (Sillence Classification)

Type I (Mild)

Type I is the mildest and most common form of OI, or brittle bone disease. People have bones that break more easily, especially during childhood, but bone shape is usually normal. Blue sclerae are typical, and hearing loss may develop in adulthood. Stature is often near normal, and fractures tend to decrease after puberty.

Type II (Perinatal Lethal)

Type II is the most severe form and typically results in death shortly before or after birth. Infants are usually born with multiple fractures, severe bone deformities, a very small size, and underdeveloped lungs. The collagen produced is severely abnormal, leading to significant skeletal fragility.

Type III (Severe)

Type III OI is characterised by progressively deforming bones, frequent fractures that often begin before birth, and severe short stature. Children typically have abnormally shaped bones, spinal curvature, a triangular face, potential respiratory problems, hearing loss, and dental issues. Life expectancy is reduced, but survival into adulthood is possible.

Type IV (Moderate)

Type IV presents with osteogenesis imperfecta symptoms of moderate severity. Children have bone fragility and frequent fractures, but usually have normal sclerae. Short stature and mild-to-moderate bone deformities are common. Hearing loss may occur later in life.

Rare Types (V, VI, VII, VIII)

• Type V: Similar to Type IV, may include calcification of the forearm membrane and hyperplastic callus formation.
• Type VI: Moderate OI with distinctive bone histology, rare mineralisation defect.
• Type VII: Resembles Type II or IV, with rhizomelia (short upper arms and thighs); associated with cartilage-associated protein gene mutations.
• Type VIII: Severe OI with growth deficiency; associated with mutations in the prolyl 3-hydroxylase 1 gene.

According to StatPearls (NCBI Bookshelf), osteogenesis imperfecta types IX, X, and XI are extremely rare recessive forms characterised by collagen-processing defects and variable skeletal dysplasia that share an autosomal recessive inheritance pattern and present with varying degrees of bone dysplasia and connective tissue abnormalities.

Causes and Genetics of Osteogenesis Imperfecta

Osteogenesis imperfecta causes are primarily attributed to genetic mutations that affect the production or quality of type I collagen. Most cases are inherited in an autosomal dominant manner, meaning only one copy of the altered gene is needed for a person to be affected. However, some rare forms are autosomal recessive or the result of new (de novo) mutations.

• Defective genes involved in collagen production. COL1A1 and COL1A2 are the most common.
• Autosomal dominant inheritance in most cases
• Autosomal recessive inheritance in rare types
• New spontaneous mutations can occur (not inherited from parents).
• Other genes involved in rare types affect collagen modification or bone mineralisation.

Complications of Osteogenesis Imperfecta

• Frequent bone fractures, sometimes from minimal trauma
• Skeletal deformities (bowed limbs, scoliosis, kyphosis, barrel chest)
• Chronic pain and limited mobility
• Hearing loss (conductive or sensorineural)
• Dental issues (brittle teeth, dentinogenesis imperfecta)
• Respiratory problems (reduced lung capacity, risk of pneumonia)
• Heart valve problems (in rare cases)
• Short stature or growth deficiency
• Delayed wound healing and easy bruising
• Fatigue and muscle weakness
• In severe cases, early death (particularly type II or severe type III)

Diagnosis of Osteogenesis Imperfecta

• Detailed medical history, including fracture history and family history
• Physical examination (looking for bone deformities, sclera colour, joint laxity)
• Genetic testing (identifying mutations in collagen-related genes)
• X-rays to assess bone structure and detect fractures and deformities
• Bone density testing (DXA scans for bone mineral density)
• Hearing tests to evaluate early hearing loss
• Dental examinations to detect dentinogenesis imperfecta

Management and Treatment Options

There is no cure for brittle bone disease, but treatment focuses on reducing fractures, maximising mobility, and improving quality of life. Osteogenesis imperfecta treatments are tailored to the individual's type and severity and may include medications, physical therapy, surgical interventions, and nutritional support.

Medications

• Bisphosphonates (the most common, slow bone breakdown and may increase bone density)
• Teriparatide (in select adults with mild forms) may stimulate new bone formation and improve bone density.
• Pain medications as needed.

Physical Therapy and Mobility Aids

Physical therapy aims to strengthen muscles, improve mobility and coordination, enhance balance, and support bone health. Low-impact exercises, aquatic therapy, and stretching are typically recommended. Mobility aids such as wheelchairs, walkers, or braces may be necessary to help prevent falls and maintain independence.

Surgical Interventions

• Rodding surgery (insertion of intramedullary rods into long bones) to stabilise and prevent fractures or deformities
• Fracture repair surgeries
• Spinal surgery for scoliosis or kyphosis correction
• Dental surgeries for dentinogenesis imperfecta

Nutritional Support

• Ensure adequate calcium, vitamin D, and protein intake to support bone health
• A balanced diet to maintain a healthy weight and muscle mass
• Monitoring for nutritional deficiencies (due to reduced mobility or dental issues)

Living with Osteogenesis Imperfecta

Individuals with brittle bone disease can lead fulfilling, active lives with multidisciplinary medical care, physical support, and adaptive strategies.

Some key considerations for living with OI include:

• Regular medical follow-up
• Safety measures to prevent falls and fractures
• Assistive devices and home modifications
• Pain management strategies
• Emotional support
• Educational accommodations and workplace modifications
• Genetic counselling for family planning

When to See a Doctor

• Frequent or recurrent fractures, often resulting from minimal or no trauma
• Bone pain or deformities
• Delayed growth or short stature
• Blue, grey, or purple tint to the whites of the eyes
• Hearing loss or dental problems
• Family history of osteogenesis imperfecta or other bone disorders

Prevention and Genetic Counselling

While there is currently no known way to prevent brittle bone disease, genetic counselling can help individuals and families understand the risk of passing on the condition to future generations.

If you have a family history of OI or have been diagnosed with the condition, consider the following:

• Consult a genetic counsellor
• Undergo genetic testing
• Discuss family planning options
• Educate family members

Conclusion

If you or a loved one is affected by osteogenesis imperfecta, remember that you are not alone. Seek support from healthcare providers, family, friends, and OI communities.

Metropolis Healthcare offers comprehensive pathology testing and health check-up services to help individuals with bone disorders like OI monitor their vitals and make informed decisions. With 220 laboratories, 4600+ service centres, and over 10,000 touchpoints across the country, we ensure technological innovation, patient-centric care, and accurate diagnostic reporting that you can trust to prioritise your well-being.

FAQs

Is osteogenesis imperfecta hereditary?

Yes, osteogenesis imperfecta is primarily a genetic disorder. However, some rare forms are autosomal recessive or the result of new (de novo) mutations.

What is the life expectancy for someone with OI?

Life expectancy varies depending on the type and severity of OI or brittle bone disease. Individuals with mild forms (Type I) often have a normal lifespan, while those with severe forms (Type II) may not survive infancy. People with moderate to severe types (III and IV) may have a reduced life expectancy due to respiratory complications and other health issues.

Can OI be cured?

Currently, there is no cure for osteogenesis imperfecta. However, various treatment options, such as medications, physical therapy, and surgery, can help manage symptoms, reduce fractures, and improve quality of life.

What activities should people with OI avoid?

People with OI should avoid high-impact activities and contact sports that increase the risk of fractures. However, low-impact exercises like swimming, cycling, and gentle stretching can help maintain muscle strength and bone health.

Which doctor treats osteogenesis imperfecta?

Treatment for osteogenesis imperfecta typically involves a multidisciplinary team of healthcare professionals, including orthopaedic specialists, endocrinologists, physical and occupational therapists, and genetic counsellors.