Osteogenesis Imperfecta (OI)
Summary
Osteogenesis Imperfecta ("Brittle Bone Disease") is a heterogeneous group of genetic disorders characterized by bone fragility and low bone mass. It is primarily caused by defects in Type I Collagen synthesis. The clinical spectrum ranges from mild (Type I) with few fractures and normal stature, to perinatal lethal (Type II). Management relies on Bisphosphonates to increase bone density and Telescopic Rodding to correct deformities. [1,2]
Clinical Pearls
The "Zebra Stripe" Sign: On X-rays of children treated with cyclical bisphosphonates (e.g., Pamidronate infusions every 3 months), distinct sclerotic lines appear in the metaphyses of growing long bones. Each line corresponds to a treatment cycle.
One = Bone: An easy mnemonic for Collagen types.
- Type 1: BONE (Osteogenesis Imperfecta).
- Type 2: CarTWOlage (Stickler Syndrome).
- Type 3: Ehlers-Danlos (Vascular).
- Type 4: Basement Membrane (Alport's).
The NAI Dilemma: OI is the most important differential for Non-Accidental Injury (Child Abuse). However, true OI is rare (1:20,000), while abuse is common. ALWAYS investigate fully.
Demographics
- Incidence: 1 in 15,000 to 20,000 births.
- Inheritance: Autosomal Dominant (85-90%). Usually a de novo mutation in severe cases.
Genetics
- Genes: COL1A1 (Chr 17) and COL1A2 (Chr 7).
- Mechanism:
- Haploinsufficiency (Quantity defect): Type I OI. Half the normal amount of collagen is made. Milder.
- Dominant Negative (Quality defect): Type II/III/IV. Mutant collagen is incorporated into the triple helix, destabilizing the whole structure. Severe.
Bone Matrix
Type I Collagen forms the triple-helix scaffold of bone (reinforced by Hydroxyapatite crystals). In OI, this scaffold is weak.
- Cortical Bone: Thin.
- Trabecular Bone: Sparse.
- Result: "Glass bones" which fracture with minimal trauma.
Type I (Mild) - Commonest
- Stature: Normal.
- Sclerae: Blue.
- Fractures: Begin when walking starts. Decrease after puberty.
- Teeth: Rare involvement.
- Hearing: 50% loss (Otosclerosis) in adulthood.
Type II (Perinatal Lethal)
- Features: Multiple intrauterine fractures, crumbled ribs ("beaded ribs"), crumpled femurs.
- Outcome: Death in utero or hours after birth (Respiratory failure).
Type III (Severe Progressive)
- Stature: Very short.
- Sclerae: Can be white or blue.
- Deformity: Severe bowing of limbs ("Sabre shins") and Kyphoscoliosis.
- Teeth: Dentinogenesis Imperfecta (translucent/brown teeth).
- Face: Triangular facies with broad forehead.
Type IV (Moderate)
- Intermediate between I and III. Sclerae often white.
- Eyes: Blue/Grey sclerae?
- Mouth: Discoloured, worn teeth?
- Spine: Scoliosis? (Common and progressive).
- Limbs: Bowing deformity? Joint hypermobility?
- Head: Macrocephaly/Triangular face.
Radiology (X-Ray)
- Osteopenia: Diffuse.
- Wormian Bones: Small irregular bones in the skull sutures (mosaic pattern).
- Fractures: Multiple, various stages of healing.
- Codfish Vertebrae: Biconcave compression fractures.
Genetics
- DNA sequencing of COL1A1 / COL1A2.
DEXA Scan
- Low Z-score (Bone Mineral Density).
Management Algorithm
OSTEOGENESIS IMPERFECTA
↓
DETERMINE TYPE
(Clinical + Genetic + XR)
↓
MILD (Type I) SEVERE (Type III/IV)
- Observe - Start **Bisphosphonates**
- Vit D/Calcium - **Physiotherapy**
- **Surgery**
↓
FRACTURE MANAGEMENT
┌─────────┴─────────┐
ACUTE CHRONIC DEFORMITY
- Light cast - SOFIELD OSTEOTOMY
- Rapid rehab - TELESCOPIC R ODS
(Muscle (Fassier-Duval)
wasting
worsens
condition)
Medical (Bisphosphonates)
- Pamidronate / Zoledronic Acid (IV).
- Mechanism: Inhibits osteoclasts (stops bone resorption).
- Effect: Increases cortical thickness. Reduces pain. Reduces fracture rate.
- Side Effects: Acute phase reaction (flu-like), Hypocalcaemia.
Surgical
- Rodding: When bone deformity prevents walking.
- Fassier-Duval Rods: "Telescopic" rods that expand as the child grows.
- Sofield Osteotomy: "Shish-kebab" procedure. Bone is cut into segments, straightened, and threaded onto the rod.
- Basilar Invagination: The skull base softens and settles onto the cervical spine. Can compress the brainstem -> Sleep apnea / Death.
- Respiratory: Scoliosis + Rib fractures = Pulmonary insufficiency.
- Hearing Loss: Early onset conductive/sensorineural.
- Type I: Normal life expectancy. Good quality of life.
- Type III: Wheelchair dependence common. Respiratory complications are life-shortening.
Key Guidelines
| Guideline | Organisation | Key Recommendations |
|---|---|---|
| OI Management | ICCBH | Start bisphosphonates in symptomatic cases. |
| Child Protection | RCPCH | Guidelines on distinguishing NAI from medical causes. |
Landmark Evidence
1. Glorieux et al (1998)
- Pivotal study introducing Cyclic Pamidronate. Showed dramatic increase in bone density and reduction in fractures in severe OI.
What is OI?
It is a condition caused by a "spelling mistake" in the gene that makes Collagen. Collagen is the protein "steel mesh" inside your bones. Calcium is the "concrete". In OI, the steel mesh is either missing or twisted. Without the steel, the concrete (bone) cracks easily.
Is there a cure?
We cannot fix the gene yet. However, we have very good treatments:
- Drip Medicine (Bisphosphonates): Used to "harden the concrete". It stops the body dissolving old bone, allowing the skeleton to thicken up.
- Magic Rods: Surgery to put metal rods inside the leg bones. These act as internal splints and grow with your child.
Can they play sport?
Contact sports (rugby/football) are usually forbidden due to fracture risk. Swimming is widely encouraged as it builds muscle (which protects bone) without impact.
Primary Sources
- Biggin A, et al. Bisphosphonate therapy for osteogenesis imperfecta. Cochrane Database Syst Rev. 2016.
- Glorieux FH, et al. Cyclic administration of pamidronate in children with severe osteogenesis imperfecta. N Engl J Med. 1998.
Common Exam Questions
- Diagnosis: "Child with blue sclerae + fractures?"
- Answer: OI Type I.
- Pathology: "Wormian bones?"
- Answer: Islands of bone in skull sutures (Classic radiographic sign).
- Treatment: "Drug class?"
- Answer: Bisphosphonates.
- Complication: "Deafness mechanism?"
- Answer: Otosclerosis (Conductive).
Viva Points
- Dentinogenesis Imperfecta: Why teeth? Because Dentine is rich in Type 1 Collagen. Enamel is not (so enamel is fine, but it flakes off the weak dentine).
- The "Warm Up" effect: When giving Zoledronic acid for the first time, 50% of kids get a fever/aches (Acute Phase Response). It rarely happens on the second dose.
Medical Disclaimer: MedVellum content is for educational purposes and clinical reference. Clinical decisions should account for individual patient circumstances. Always consult appropriate specialists.