Overview
Osteogenesis Imperfecta
1. Clinical Overview
Summary
Osteogenesis Imperfecta (OI) is a genetic disorder of Type I collagen synthesis causing fragile bones, susceptibility to fractures, and other connective tissue abnormalities. Severity ranges from mild (Type I) to lethal perinatal (Type II). Treatment aims to reduce fractures and improve quality of life.
Key Facts
| Aspect | Detail |
|---|---|
| Cause | Mutations in COL1A1/COL1A2 (Type I collagen genes) |
| Inheritance | Mostly autosomal dominant |
| Key Feature | Fragile bones - fractures from minimal trauma |
| Classic Signs | Blue sclerae, dentinogenesis imperfecta, hearing loss |
| Medical Treatment | Bisphosphonates (increase bone density) |
Clinical Pearls
- Blue sclerae: Thin sclera allows choroidal veins to show through
- NAI differential: OI fractures occur with minimal trauma; corner fractures and rib fractures in OI are LESS common than in NAI
- Wormian bones: Multiple irregular bones at skull sutures - characteristic
- Type I = Mildest: Most common form, fractures decrease after puberty
2. Epidemiology
Incidence
| Type | Incidence |
|---|---|
| All types | 1 in 10,000-20,000 births |
| Type I | Most common (~50%) |
| Type II | ~10% (lethal) |
Genetics
| Type | Inheritance | Notes |
|---|---|---|
| I | AD | Mild |
| II | AD (new mutation) | Lethal perinatal |
| III | AD (or AR) | Severe, progressive |
| IV | AD | Moderate |
3. Pathophysiology
Collagen Defect
COL1A1/COL1A2 Gene Mutation
↓
Abnormal Type I Collagen Production
↓
Defective Bone, Skin, Dentin, Sclera, Ligaments
↓
FRAGILE BONES + OTHER CONNECTIVE TISSUE ABNORMALITIES
Type I Collagen Distribution
| Tissue | Manifestation |
|---|---|
| Bone | Fractures, deformity |
| Sclera | Blue appearance |
| Dentin | Dentinogenesis imperfecta |
| Inner ear | Hearing loss (otosclerosis-like) |
| Skin | Thin, easily bruised |
| Ligaments | Hypermobility |
4. Clinical Presentation
Sillence Classification
| Type | Severity | Features |
|---|---|---|
| I | Mild | Blue sclerae, fractures in childhood, normal/near-normal stature |
| II | Lethal | Multiple intrauterine fractures, perinatal death |
| III | Severe | Progressive deformity, short stature, grey sclerae |
| IV | Moderate | Normal sclerae, mild-moderate deformity |
Clinical Features
| Feature | Description |
|---|---|
| Fractures | From minimal trauma, often before walking |
| Blue sclerae | Type I especially |
| Dentinogenesis imperfecta | Opalescent, discoloured teeth |
| Hearing loss | Conductive or mixed, adult onset |
| Wormian bones | Extra skull bone islands |
| Short stature | Type III especially |
| Hypermobility | Joint laxity |
| Triangular facies | |
| Barrel chest |
5. Clinical Examination
Systematic Assessment
| System | Findings |
|---|---|
| Sclerae | Blue (Type I), grey/white (other types) |
| Teeth | Discoloured, translucent (DI) |
| Limbs | Deformity, shortening, bowing |
| Height | Short stature (especially Type III) |
| Joints | Hypermobility |
| Hearing | May be reduced |
| Spine | Kyphoscoliosis |
Distinguish from NAI
| Feature | OI | NAI |
|---|---|---|
| History | Minimal trauma | Inconsistent history |
| Fracture types | Long bones, mostly | Rib, metaphyseal corner |
| Associated features | Blue sclerae, DI, family hx | Bruising, other injuries |
| Bone density | Reduced | Normal |
6. Investigations
Diagnostic Tests
| Test | Finding |
|---|---|
| X-rays | Fractures, osteopenia, Wormian bones |
| DEXA | Reduced bone mineral density |
| Genetic testing | COL1A1/COL1A2 mutations (confirmatory) |
| Collagen analysis | Skin fibroblast biopsy (historical) |
X-ray Features
| Finding | Description |
|---|---|
| Osteopenia | Generalised |
| Wormian bones | Skull |
| Thin cortices | Long bones |
| Fractures | Various healing stages |
| Bowing | Long bone deformity |
7. Management
Medical Treatment
| Drug | Details |
|---|---|
| Bisphosphonates | IV Pamidronate or Zoledronate cycles |
| Mechanism | Reduce osteoclast activity, increase bone density |
| Benefits | Fewer fractures, less pain, improved mobility |
| Monitoring | DEXA, vertebral imaging |
Surgical Treatment
| Procedure | Indication |
|---|---|
| Intramedullary rodding | Correct and stabilise bowing deformities |
| Telescoping rods | Fassier-Duval - grow with the child |
| Spinal surgery | Scoliosis correction |
Multidisciplinary Care
| Specialist | Role |
|---|---|
| Orthopaedics | Fracture management, surgery |
| Genetics | Diagnosis, counselling |
| Physiotherapy | Mobility, strengthening |
| Audiology | Hearing assessment |
| Dentistry | Dentinogenesis imperfecta |
| Endocrinology | Bone health optimisation |
Adjuncts
| Intervention | Details |
|---|---|
| Vitamin D | Ensure sufficiency |
| Calcium | Adequate intake |
| Physiotherapy | Low-impact exercise, hydrotherapy |
| Mobility aids | Wheelchairs, walkers as needed |
8. Complications
| Complication | Notes |
|---|---|
| Recurrent fractures | Main morbidity |
| Progressive deformity | Bowing, short stature |
| Scoliosis | May be severe |
| Basilar invagination | Cervical spine - serious |
| Hearing loss | Requires monitoring |
| Cardiopulmonary | Restrictive lung disease from chest deformity |
9. Prognosis & Outcomes
| Type | Prognosis |
|---|---|
| Type I | Normal lifespan, fractures decrease after puberty |
| Type II | Lethal perinatally |
| Type III | Significantly reduced life expectancy, wheelchair-dependent |
| Type IV | Near-normal lifespan with treatment |
10. Evidence & Guidelines
| Organisation | Key Points |
|---|---|
| OI Foundation | Patient resources |
| Brittle Bone Society | UK charity, support |
| ISCD | DEXA guidelines in children |
11. Patient / Layperson Explanation
What is OI? Osteogenesis Imperfecta (OI), often called "brittle bone disease," is a genetic condition that makes bones break very easily. It happens because of a problem with the protein (collagen) that gives bones their strength.
What are the signs?
- Bones that break easily, sometimes from very minor bumps
- Blue or grey colour to the whites of the eyes
- Dental problems
- Hearing loss (in some cases)
- Being shorter than average (in some types)
How is it treated?
- Medications: Bisphosphonates (given as a drip) help strengthen bones
- Surgery: Rods inside the bones to straighten and strengthen them
- Physiotherapy: Keeping muscles strong and joints mobile
- Support: Wheelchairs, walking aids when needed
What's the outlook? This varies depending on the type. Many children with milder OI grow up to live normal lives. With modern treatments, even those with more severe types are doing better than ever before.
Is it my fault? No - OI is usually a random genetic change. It's not caused by anything during pregnancy.
12. References
- Sillence DO, et al. Genetic heterogeneity in osteogenesis imperfecta. J Med Genet. 1979.
- Forlino A, Marini JC. OI. Lancet. 2016.
- Brittle Bone Society. www.brittlebone.org
- OI Foundation. www.oif.org