osteogenesis imperfecta

1. OSTEOGENESIS IMPERFECTA
Dr. LOKESH SHAROFF
Orthopedic Surgeon, Mumbai, India

2. 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.

3. • osteogenesis imperfecta congenita (also
known as Vrolik disease)
• osteogenesis imperfecta tarda (also known as
Ekman-Lobstein disease

4. 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.

5. • 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

6. • 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.

7. 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

10. • 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

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

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

13. 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

14. • 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

15. • 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

16. • 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

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

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

19. 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.

20. • 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.

21. • 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.”

22. • 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.

23. • Muscles are hypotonic.
• Blue sclera--- opacity in the periphery of the
cornea, and Retinal detachment may occur.
• Deafness-- usually beginning in adolescence or
adulthood.

28. 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.

29. • 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.

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

31. • 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

36. 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

37. 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.

38. • 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

39. • 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.

40. 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

41. 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

42. • 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

43. 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.

44. 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

45. • 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

46. • Nonambulatory patients-- use of motorized
wheelchairs

47. 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

48. • 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

49. • 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.

50. • 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

51. 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

52. • 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

53. COMPLICATIONS
• Hyperplastic callus formation
• Tumors-- Osteogenic sarcoma
• aneurysmal bone cyst, and unicameral bone
cyst
• Basilar impression

54. THANK YOU