Lecture on Osteogenesis Imperfecta for MBBS students.

1. CASE HISTORY
• 1 yr old child Fractures shortly after bipedal
mobility (from crawling to walking stance).
• Biological father has also has a history of several
broken bones as a child and has recently begun
to develop bilateral hearing loss.
• Patient is 75th percentile for weight and height
for his age and has a slight bluish gray tint to the
sclera.

2. Osteogenesis Imperfacta
Hereditary condition resulting from a decrease
in the amount of normal Type I collagen
Type I collagen ( important for )
Bone
Ligaments
Teeth
White Sclera
Skin

3. Type I collagen deficiency can result from
decreased collagen secretion
production of abnormal collagen
Both Autosomal dominant and Autosomal recessive forms
Can be severe or mild (Tarda)
Osteogenesis Imperfecta

4. Epidemiology
 Incidence : 1 casefor
every 20,000livebirths
 Equallycommon in males
andfemales
 Nopredilection fora
particular race

5. • Earliest known case of osteogenesis imperfecta in a partially
mummified infant’s skeleton from ancient Egypt now housed in
the British Museum in London.
• OTHER NAMES
• LOBSTEIN DISEASE
• BRITTLE- BONE DISEASE
• BLUE-SCLERA SYNDROME
• FRAGILE-BONE DISEASE

6. GENETICS
Quantitativedefectsof type1collagen:
mutations on COL1A gene
Qualitativedefectsof type1collagen: autosomal
dominant mutations on either the
COL1A or the COL1Bgene

9. Pathologic changes seen in all tissues in which type 1
collagen is an important constituent -bone, ligament,
dentin, and sclera

10. Orthopaedic manifestations
Bone fragility and fractures
fractures heal in normal fashion initially
but the bone is does not remodel- lead to
progressive bowing
Ligamentous laxity
Short stature
Basilar invagination-the tip of the odontoid
process projects above the foramen magnum
Olecranon apophyseal avulsionfx

11. Scoliosis
Codfish vertebrae(compressionfx)
Wormian skullbones
(puzzle pieceintrasutural skullbones)

12. Non-Orthopaedic manifestations
Blue sclera
Hearing loss
Dentinogenesis imperfecta
brownishopalescentteeth

13. Symptoms
Mild cases
multiple fractures duringchildhood
Severe cases
present with fractures at birth and can be fatal
Number of fractures typically decreases as patient ages and
usually stops after puberty
But deformity persist.
Basilar invagination
Brain Stem dysfunction apnea, altered
consciousness, ataxia, or myelopathy
usually in third or fourth decade of life, but can
be as early as teenage years

14. Physical exam
Multiple fractures leads to
Saber shin appearance of tibia
Bowing of long bones
Scoliosis

15. Physical Examination
 Sillence classification : 4
types on basis of clinical
and radiologicfeatures
 Dentinogenesis
imperfecta denoted as
subtype B,whereas OI
without dentinogenesis
imperfecta isdenoted as
subtypeA

16. Sillence Classification of Osteogenes Imperfecta
(simplified)
Type I
Mildest form. Presents at preschool age (Tarda).
Autosomal dominant
Blue sclera
Hearing deficit in 50%.
Divided into type A and B based on tooth involvement
Type II
Autosomal recessive / AD
Blue sclera
Lethal in perinatal period

17. Type III
Autosomal recessive
Normal sclerea
Fractures at birth.
Progressively short stature.
Most severe survivable form
Type IV
Autosomal dominant normal
Moderate severity.
Bowing bones and vertebral fractures are common.
Hearing normal.
Divided into type Aand B based on tooth involvement

18. Type5
• Autosomal dominent
• Samefeatures astype 4
• Different histologically ( bone appears mesh
like)
• Calcification of radio ulnarinterosseous
membrane

21. Diagnosis
Diagnosis is based on family history associated
with typical radiographic and clinical features
No commercially available diagnostic test
Laboratory values are typically within normal range
Fibroblast culturing to analyze type I collagen (positive in 80% of
Type IV) can be used for confirmation of diagnosis in equivocal
cases

22.  Skin biopsy: collagen can be isolated from cultured
fibroblasts and assessed for defects, with an accuracy of
85-87%
 Bone biopsy : show changes in concentrations of
noncollagenous bone proteins, such as osteonectin,
sialoprotein, and decorin

23. DNA
 DNA blood testing for gene defects has an
accuracy of 60- 94%.
 Samples are obtained during chorionic villus
sampling performed under ultrasonographic
guidance when a mutation in another member of
the family is already known

24. Prenatalultrasonography :
 Useful in evaluating OItypesII
andIII
 Detects limb-length abnormalities at
15-18weeks
 Supervisualization of intracranial
contents causedby decreased
mineralization of calvaria(also calvarial
compressibility), bowing ofthe long
bones,decreasedbone length (especially
of the femur), and multiple rib
fractures

25. Radiographs
Thin cortices Generalized osteopenia
Long bone thin and bowed-shepherd’s
crook deformities of the femurs
Excessive callus formation and popcorn bones
Pelvis may show acetabular protrusion
Fractures that are at different stages of healing
The vertebra maybe biconcave.
Skull changes - Wormian bones

27. TREATMENT
NOCURE
Orthotics: limited role, to stabilize lax joints
(eg,ankle and subtalar joints withankle-foot
orthoses) and to prevent progressive deformities
andfractures.
Provide walking aids, specialized wheelchairs, and
home adaptation devices to help improve
patient’s mobility andfunction

28. Treatment
Bone Deformity
Scoliosis
Fracture
Prevention Treatment

29. PatientEducation
Patients with OI: well motivated and keen to
achieve as much as possible despite their
physical limitations
Education of parents and families :to know
how to position child in crib and how to hold
child so as to minimize risk of fractures while
maintaining bonding and physical stimulation

30. DIETANDACTIVITY
Nutritional evaluation and intervention
paramount to ensure appropriate intakeof
calcium, phosphorus, and vitamin D
Caloric management important, particularly in
adolescents and adults with severeforms ofOI
Physicaltherapy, in form of comprehensive
rehabilitation programs, directed toward
improving joint mobility and developingmuscle
strength

31. Treatment of Fractures
Fracture prevention
Early bracing
Decrease deformity.
Stabilize lax joints.
Decrease fractures incidence.
Bisphosphonates

32. BISPHOSPHONATES
 Synthetic analogues of pyrophosphate that inhibit
osteoclast- mediated bone resorption on the endosteal
surface of bone by binding to hydroxyapatite.
 Unopposed osteoblastic new bone formation on the
periosteal surface results in an increase in cortical
thickness.

33. Pamidronate
Injectable bisphosphonate
(Cyclic Intravenous )
Increases cortical bone thickness
Increase bone mass and density.
Decreases the incidence of fractures.
Relieves chronic bonepain.
Increases activity levels.
Decreases the reliance on mobility aids.
Increases the height of the collapsed
vertebral bodies.
BUT
Notdecreasetheincidenceofscoliosis.
Zebralines
Radiographically Pamidronate therapy creates growth lines in the bone

34. Growth hormone:
act on growth plate, stimulate osteoblast function,
possibly via IGF-1 ,IGFBP-3

35. Bone marrowtransplantation
Used with somesuccess
Introduces normal marrow stem cells that could
potentially differentiate into normal osteoblasts,
Problems of graft rejection and graft versus host
reactions limit thisapproach.
FUTURE

36. Fracture treatment
Nonoperative
child is less than 2 years
treataschildwithoutOI
Operative
Fixation with INTRAMEDULLARY
RODS (TELESCOPING)
patients > 2 years
allow continued growth

37. conservative Treatment
in OIFractures
Children <24 months

38. RODDING OPTIONS
RUSH NAIL
TELESCOPING NAIL

39. Treatment of Long Bone Deformities
Realignment Osteotomy with rod fixation
(Sofield-Miller procedure)- KEBAB OSTEOTOMY
Indicated in severe deformity to
Correct the deformity
Reduce fracture rates
Techniques include
Nontelescopic devices
Telescopic devices

40. Treatment of Scoliosis
Observation
Curve less than 45°
Bracing is ineffective
Operative
posterior spinal fusion
Indications
for curves > 45 °in mild formsand
> 35 °in severe forms
Technique
Challenging due to fragility of bones
Use allograft instead of iliac crest autograft
Large blood loss

41. .
Acute / Stress Fracture Deformity with Chronic
StressFracture

42. FRACTURE --------OSTEOPOROSIS---------REFRACTURE
Early Surgery and PreparatoryPamidronate

43. Never useplate in OI

44. Plating
MUST BEAVOIDEDAS
HIGH RISK OFSTRESS
FRACTURE.

45. 7year old child withOI
Plating done forfemur
fracture
Deformity appears
above and belowthe
plate due to stress
shielding of bone

46. Revised to F– D
TelescopingRod

47. 20 month old girl,
repeated femur
fractures, unable to stand
?delayed milesones

48. Four months postop

49. Nine Months post-op
Standing withsupport

50. • 10 year old child
• OI?TypeIII, progressive deformity
• 5 cycles of Pamidronate received
• No surgery done

51. How early to NAIL?
Rodding :before orafter
bisphosphonatetreatment
Choice ofRod

52. ClassicalShishKabab Surgery
Very Narrow IM Canal:2mm
Rodinserted
Spicafor 6 weeks and followed
by splints

55. ThankYou