Osteogenesis Imperfecta

Defect

 

Abnormality of type 1 collagen

- amino acid substitution of glycine with another amino acid

- prevents triple helix formation

 

Many many deformities described

- some 286 mutations of Type 1 collagen described

 

Sillence Classification

 

There are actually now 7 

 

Type I

- mild

- AD

- blue sclera

 

Type II

- lethal in utero

- AR

- blue sclera

 

Type III

- severe

- AR

- white sclera

- multiple deformities without intervention

- wheelchair bound and non ambulatory

 

Type IV

- moderate to severe

- white sclera

- AD

- very rare

 

DDx

 

NAI

Rickets

 

Diagnosis

 

Skin biopsy

- assessment of type 1 collagen

- fibroblast cell culture

 

DNA study

 

Skeletal Manifestations

 

Frequent multilevel fractures with limb deformity

- tibia

- femur

- forearm

 

Osteogenesis Imperfecta ForearmOsteogenesis Imperfecta Wrist

 

Osteogenesis Tibial BowOsteogenesis Imperfecta Tibial Bow 2

 

OI ForearmOI Shoulder

 

Coxa vara

- femoral neck shaft < 110o

- correct with multiple osteotomies

 

Kyphoscoliosis

 

Surgery

- indicated for curve reaching 40o as will be progressive and non flexible

- > 60o impairs respiratory function

 

Problems

- bony fragility

- increased use of pedicle and TP hooks and sublaminar wires

 

Basilar impression / invagination

 

Very serious problem

- the foramen magnum invaginating into the posterior fossa

- leads to stenosis with resultant hydrocephalus 

- compression of the cerebellum, brain stem, and cervical cord

 

Lateral cervical spine radiograph

- upward migration of the cervical spine into the base of the skull

- deformity may be subtle and requires careful scrutiny of the radiographs

 

Various descriptions of the characteristic skull shape

- Darth Vader

 

Extraskeletal Manifestations

 

Blue sclera 

- due to translucent sclera can see underlying choroid and blood vessels

- due to defect type 1 collagen

 

Dentinogenesia imperfecta 

- teeth appear brownish or bluish

- are soft, translucent and prone to cavities

- defect type 1 collagen

 

Hearing problems

- defect hearing bones

 

Fragile skin and fragile capillaries

 

Valvular Disease

 

Mitral prolapse and Aortic Regurgitation

 

Management

 

Nonoperative Management

 

Bisphosphonates

 

Increase BMD and cortical thickness and cancellous trabeculation

- reduces bone pain

- decrease fracture rate

- maintains shape of long bones and vertebrae

 

Mechanism of action

- inhibits osteoclasts

 

Pharmocokinetics

- very poor bioavailability (.6 - 7)

- incorporated into skeleton

- long half life there (1.5 - 10 years)

 

Problems

- need period off medications

- doesn't decrease fracture healing but probably does decrease osteotomy healing (i.e. avoid around time of IM rodding)

- osteonecrosis of the jaw: a rare side effect in adults, not seen in children

 

Results

 

Glorieux et al NEJM 1998

- increased BMD by 40%

- reduced fracture rate by 1.7 per year

- evidence new bone formation in vertebrae

- did not alter rate fracture healing

 

Bone marrow transplant

 

Increased mesenchymal stem cells

 

Operative Management

 

Goals

 

Prevent fractures

Treat or prevent deformity

 

Technique

 

Multilevel osteotomy with IMN

- must be expandable or get fracture and deformity below level

 

Expandable telescopic IM rods

 

Concept

- lengthen as the bone grows

- male and female portions

- lock in epiphysis top and bottom

 

Sheffield Rods

- T piece

- 20% revision at 5 years

 

Fassier-Duval Rods

- epiphyseal portion is threaded