OSTEOGENESIS IMPERFECTA

Dr. LOKESH SHAROFFOrthopedic Surgeon, Mumbai, India

INTRODUCTION

• Osteogenesis imperfecta is a genetic disorder of connective tissue with the clinical feature of bone fragility, long-bone fractures, skeletal deformity, blue sclerae, hearing loss, and fragile, opalescent teeth (dentinogenesis imperfecta).

• Less severe manifestations may include generalized ligamentous laxity, hernias, easy bruisability, and excessive sweating.

• osteogenesis imperfecta congenita (also known as Vrolik disease)

• osteogenesis imperfecta tarda (also known as Ekman-Lobstein disease

PATHOPHYSIOLOGY

• Defect in the genes responsible for encoding type I collagen

• Leading to absolute reduction in the amount of normal type I collagen in bone or its replacement with a poorly functioning mutant collagen.

• The formation of both enchondral and intramembranous bone is disturbed. The bone trabeculae are thin and lack an organized trabecular pattern.

• The intracellular matrix is reduced. • osseous tissue almost always of the woven

variety. • The secondary centers of ossification in the

epiphysis are delayed in maturation

• Gross anatomic findings--- consist of porosis (osteopenia), diminution in size, and skeletal deformities secondary to fracture and asymmetric physeal growth disturbance.

• The cartilaginous epiphyseal ends of the long bones are disproportionately large and have some irregularity of the articular surface.

SHAPIRO'S CLASSIFICATION

• Osteogenesis imperfecta congenita A • In utero or birth fractures; short, broad,

crumpled femora and ribs • F/H/O--0% • Deaths---15/16 (94%) • One survivor wheelchair bound

• Osteogenesis imperfecta congenita B • In utero or birth fractures, normal long bone

contours, no chest deformity • F/H/O--4% • Death---2/27 (8%) • 59% wheelchair bound; 33% at least

household ambulators

• Osteogenesis imperfecta tarda A • Fractures after birth but before walking • F/H/O---11% • Death--0/21 (0%) • 33% in wheelchair; 67% ambulatory

• Osteogenesis imperfecta tarda B • Fractures after walking • F/H--76% • Death--0/21 (0%) • 100% ambulatory

CLASSIFICATION--- SILLENCE

• IA• AD• Teeth-- N• Long bone deformity--Moderate• Short stature, 2% to 3% below mean• Hearing loss—40%• Prognosis--Fair• Eyes--Distinctly blue throughout life• Scoliosis and kyphosis in 20%• Wormian bones on radiographs

• IB• AD• Dentinogenesis imperfecta• Long bone deformity--Moderate• Short, 2% to 3% below mean• Hearing loss—40%• Prognosis--Fair• Distinctly blue throughout life• Scoliosis and kyphosis in 20%• Wormian bones on radiographs

• II• AR• Teeth--Unknown (because of Perinatal death)• Crumbled bone (accordion femora) marked• Unknown (because of perinatal death) • Perinatal death• Blue sclera• Marked absence of ossification

• III• AR• Dentinogenesis imperfecta• Progressive bowing of the long bones and spine• Severe—smallest of all patients with Osteogenesis

imperfecta • Nonambulatory, wheelchair bound• Bluish at birth, become less blue with age, white in

adult• Kyphoscoliosis• Hypoplastic, more ossified than in type II• May die in third decade• Wormian bones

• IVA• AD• teeth-- N• Moderate• Short stature• Low frequency• Fair• Normal• Kyphoscoliosis• Hypoplastic• Wormian bones

• IVB• AD• Dentinogenesis imperfecta• Moderate• Short stature• Low frequency• Fair• Sclerae--Normal• Kyphoscoliosis• Hypoplastic• Wormian bones

CLINICAL FEATURES• In the severe congenital form (Sillence's type

II)--- multiple fractures from minimal trauma during delivery or in utero cause the limbs to be deformed and short. Crepitation--- by palpation at fracture sites. The skull is soft and membranous.

• usually fatal, with death secondary to intracranial hemorrhage or respiratory insufficiency caused by incompetency of the rib cage; the infant is stillborn or lives only a short time.

• In the nonlethal forms (Sillence's types I, III, and IV) --- fractures can occur after the slightest injury. The femur is more commonly fractured than the tibia. Fractures heal at a normal rate; nonunion is relatively rare but does occur. Growth may be arrested by multiple microfractures at the epiphyseal ends.

• Typically, an anterolateral bow or proximal varus deformity of the femur develops;

• an anterior or anteromedial bow of the tibia may develop.

• Acetabular protrusion may be present.• The humerus-- angled laterally or anterolaterally. • The forearm rotation is often severely limited.

The elbow joint has cubitus varus with flexion contracture.

• The faciocranial disproportion--- gives the face a triangular, elfin shape.

• The ears are displaced downward and outward. The configuration of the skull --- soldier's helmet and is called “helmet head.”

• Spinal deformity---Scoliosis or kyphosis, or both may be present.

• The most common type of curve is thoracic scoliosis. Spondylolisthesis, Cervical spinal fractures

• Short stature • Hypermobility of joints --- Pes valgus, recurrent

DDH can occur. • Adults may be predisposed to rupture of the

patellar ligament or Achilles tendon.

• Muscles are hypotonic. • Blue sclera--- opacity in the periphery of the

cornea, and Retinal detachment may occur. • Deafness-- usually beginning in adolescence or

adulthood.

Radiographic Findings • SEVERE FORM--- The long bones of the limbs

are short and wide with thin cortices. The diaphyses are as wide as the metaphyses.

• numerous fractures in various stages of healing. Multiple rib fractures and atrophy of the thoracic cage.

• “Popcorn” calcifications in the metaphyseal and epiphyseal areas of long bones close to the growth plate. appear in childhood and usually resolve after the completion of skeletal growth.

• The skull has a mushroom appearance with very thin calvaria with marked paucity and delay in ossification.

• Wormian bones are present• The spine shows marked osteoporosis;

biconcave vertebrae, Scoliosis and kyphosis. • In the hip, coxa vara and acetabular protrusion

may be found.

• Plain film• This is the preferred initial examination.• head, neck & spine : • Wormian bone• Kyphoscoliosis• Codfish vertebrae• Vertebral compression #s• Pectus excavatum/carinatum

• general :• Severe osteoporosis –deformed bones–cortical thinning–hyperplastic callus formation–zebra stripe sign-- cyclic bisphosphonate

treatment produces sclerotic growth recovery lines in the long bones –formation of pseudoarthroses at sites of

healing fractures

PRE-NATAL ULTRASOUND

• often useful in the type II (peri natal) and type III forms.• may show decreased calvarial ossification

– this may result over visualisation of fetal brain detail– the skull may deform / compress with transducer pressure

• may show evidence of fractures – long bones may appear shortened and / or angulated as a

result– there may be a sonographic gap along the length of a long

bone – rib may nave a beaded appearance

• there may be presence of polyhydramnios

DIFFERENTIAL DIAGNOSIS

• In the newborn period and in early infancy, Sillence's type II OI should be distinguished from congenital hypophosphatasia-- a lethal affection, laboratory tests will show a low phosphatase level in serum, lack of alkaline phosphatase activity in leukocytes, and excessive excretion of phosphorylethanolamine in urine.

• Camptomelic dwarfism with osteogenesis imperfecta because of the congenital bowing and angulation of the long bones. Fractures, however, are not a feature of this type of dwarfism

• Patients with PYKNODYSOSTOSIS may have a propensity to fracture. Patients with this condition will have bony sclerosis evident on radiographs, persistently wide cranial fontanelles, micrognathism with absence of the mandible, hypoplasia of the clavicles, and osteolysis of the terminal phalanges of the fingers.

TREATMENT

• The ideal treatment of osteogenesis imperfecta would be to correct the basic genetic defect by replacing the defective COL1A1 or COL1A2 gene with a normal one. That capability, of course, does not yet exist.

• MEDICAL TREATMENT--- • Bisphosphonates • Bone marrow transplantation

BISPHOSPHONATES

• Pamidronate-- is administered I/V in dosages ranging from 15 mg given every 20 days to 7 mg/kg/yr given every 4 to 6 months,

• improvement in generalized bone pain and a reduced incidence of fractures

• Delayed healing of fractures or osteotomies has been reported in children treated with pamidronate

• Oral agent • Alendronate-- given over a period of 4 years

was associated with reduced frequency of fracture and improved ambulatory or mobility status and improved Bone mineral density

ORTHOPAEDIC TREATMENT

• The goal of orthopaedic treatment is--- • to maximize the affected patient's function,• prevent deformity and disability resulting

from fractures, • correct deformities that have developed, and• monitor for potential complicating conditions

associated with osteogenesis imperfecta.

ORTHOTIC TREATMENT • Infants with birth fractures usually need only

careful, supportive handling to prevent further injury.

• If long-bone fractures are unstable, minimal external splinting may be used to stabilize the affected limb--heal within a week or two

• avoid excessive or prolonged immobilization at any age --aggravate the osteopenia and induce joint stiffness, either of which in turn increases the risk for fracture

• Protective bracing to prevent fractures and aid in ambulation is a mainstay in the conservative management of patients with osteogenesis imperfecta

• lightweight plastic and metal hip-knee-ankle-foot orthoses (HKAFOs) –

• for effective lower extremity bracing • To allow patients to stand or walk• To reduce the incidence of lower extremity

fractures • Lightweight air-filled fluted trouser splints-- an

effective simple alternative to HKAFOs

• Nonambulatory patients-- use of motorized wheelchairs

Management of Long-Bone Fractures

• General observations--- • most fractures heal, • recurrent fractures are common, and • inherent osteopenia may be aggravated by

prolonged immobilization, thus making the patient even more susceptible to fracture

• General management principles are –• fractures should be immobilized only until

symptoms resolve, with the minimum amount of external immobilization required to provide comfort

• encourage to return judiciously to their usual level of activity as soon as feasible

• Radiographs are not always required, especially if the fracture is not grossly unstable or does not result in a new deformity

• Fractures in a newborn, if unstable or interfering with normal handling, may be splinted with padded tongue depressors, padded aluminum splints, or plaster splints. Usually, only a week or two of splinting will be required until the fracture has stabilized.

• Fractures in an older child or adult, with relatively minor involvement, should be treated by means appropriate to the fracture, including reduction and casting, percutaneous pinning, or internal fixation.

• general principle, intramedullary fixation is preferable to plates and screws whenever possible because of the stress risers produced by the latter

• displaced fracture of the olecranon-- often occur bilaterally, though not usually simultaneously-- can be managed by tension band wiring

• Nonunion is an uncommon sequela of fracture or surgery, but it does occur--most commonly in the femur and humerus >> the radius, ulna, and pubis

Management of Long-Bone Deformity • most important indication for surgical correction

of long-bone deformity is-- repeated fractures induced by the deformity

• to remove the deformity to allow bracing either for protection against further fractures or to aid in ambulation

• Long-bone deformity in infants and children can be corrected by–

• closed osteoclasis without intramedullary fixation,

• by closed osteoclasis with percutaneous intramedullary fixation, and

• by open osteotomy with internal fixation (Sofield's Procedure)

• external fixation by the Ilizarov circular fixator with wire fixation and osteotomy-- to correct long-bone deformity in young adult patients

COMPLICATIONS

• Hyperplastic callus formation• Tumors-- Osteogenic sarcoma • aneurysmal bone cyst, and unicameral bone

cyst• Basilar impression

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