Osteogenesis imperfecta is a genetic disorder characterized by fragile bones that break easily from minor trauma. The document discusses the various types of osteogenesis imperfecta based on severity and inheritance. Clinical features include fractures, skeletal deformities, blue sclera, and hearing loss. The disorder results from defects in the genes that encode type 1 collagen. Treatments include conservative management with bracing and bisphosphonates to reduce fractures, and surgical interventions like intramedullary rods to correct deformities and facilitate mobility.

1. OSTEOGENESIS IMPERFECTA

2. INTRODUCTION
• Genetic disorder of the connective tissue characterised by long
bone fractures, skeletal deformity, blue sclera, hearing loss, fragile
teeth.
• Disease can be so severe that the affected child may be born with
intra-uterine fractures, crumpled ribs, fragile cranium.
• 80-90% of the cases have genetic background
• Type1 collagen defect
• Inheritence : Autozomal dominant
• Homozygous autosomal recessive
• Sporadic.
• SYNONYMS : BRITTLE BONE DISEASE, VROLIK’S DISEASE,
FRAGILITUS OSSIUM.

3. HISTORY
• Condition was first described by Ekman
• Term coined by Vrolik 1894
• Broadly divided into 2 groups – congenita and tarda by
E. Looser in 1906
• In 1918 Van der Hoeve described the occurrence of
fragile bones, in combination with blue sclera and early
deafness as a distinct inherited syndrome.

4. AETIO-PATHOLOGY
• Defect in the gene encoding collagen type1 protein (major
structural protein found in bone and connective tissue)
• Collagen is a triple helical protein strand – 2 alpha1 strands and 1
alpha2 strand.
• Precursor subunits: pro alpha1 and pro alpha2
• Genes encoding – COL1A1 for pro alpha1
COL1A2 for pro alpha 2
Synthesised in the rough endoplasmic reticulum.
Pro alpha1 chains and pro alpha2 chains combine to form type1 pro
collagen molecule.
Carboxy terminal end of all these chains interacts and propagates to
the amino terminal end resulting in cross linking of these 3 chains.
The formed pro collagen molecule is processed extra cellularly.

5. Defect in the metabolism
• Qualitative and Quantitative.
• No formation of type 1 collagen is classified
under quantitative error.
• Patients with this defect have a STOP codon in
the required gene so that no mRNA synthesis
occurs. – No protein synthesis.
• Qualitative error :
• Substitution or deletion in the glycine peptide
residue of the poly peptide chain – synthesis of
abnormal and ineffective collagen.

6. CLINICAL FEATURE.
• Degree of severity varies with the disease types.
Multiple fractures from minimal trauma at the time of
delivery.
Intracranial haemorrhage
Respiratory insufficiency due to incompetence of rib
Cage.
Growth arrested due to multiple micro fractures at the
epiphyseal ends.
Olecranon fractures are most common.

7. Spine – kyphosis, scoliosis
Poor dentition (blue brown and opalescent colour)
Blue sclera.
Early onset deafness.
Multiple joint contractures.
Frontal bossing
Depressed frontanelle.
Protrusio acetabuli
Coxa vara
Basilar invagination a/w macrocephaly and hydrocephalus
apnoea, alt sensorium, ataxia, nystagmus, papilloedema.

10. Classification
• SILLENCE CLASSIFICATION:
• Type 1 : Most common
Autosomal dominant
Blue sclera
Impaired hearing
Type 2 : Perinatally lethal form
Autosomal dominant/ recessive
Blue sclera
Large skull, wormian bones.
Crumples ribs – resp insufficiency

11. • Type 3 : Classical form
Marked deformities
Marked kypho-scoliosis
Marked joint laxity
Autosomal recessive or sporadic
Blue sclera resolving with age
Type 4: Autosomal dominant
Light sclera
Survival to adulthood with good quality of life

12. • Type 5 : Autosomal dominant
Irregular mesh like lamellar bone.
Hypertrophic callus formation after fracture
Calcification of interosseous membrane
Type 6 : Mineralisation defect
Low mineral density
Frequent fractures
Long bone deformity
Normal vitD levels.
Normal coloured sclera.
Type 7 : Autosomal recessive
Limb shortening
Coxa vara

13. Shapiro classification
• Congenita A – Fractures in utero/ at birth
Crumpled ribs and femur
Mortality rate 94%
Congenita B – Fractures in utero / at birth
Normal bone contour
Mortality – 8%
Wheel chair bound 59%
Ambulatory 33%
Tarda A - Fractures before walking age
Tarda B - Fractures after walking age
( 100% ambulatory)

14. Genetic classification

15. Investigations
• Serum Calcium
• Serum Phorphorous
• Alkaline phosphatase
• Xrays
• Genetic study : COL1A1 , COL1A2, CTRAP, LEPRE, SERPIN F1,
SERPINH1, etc

16. Xray findings
• Type 1 : Osteopenia and olecranon fractures
• Type 2 : Concertina collapse of femur,
bone shortening or widening

17. • Type 3 : Flaring of metaphysis,
Extreme bowing due to multiple fracture
Wormian bones in the skull
Protrusio acetabuli
Spine deformities (biconcave vertebrae,
compression fractures)

19. Type 4 : Moderate deformities
Type 5 : Hyperplastic callus formation, interosseous
membrane calcification, irregular calcification extending into
metaphysis (popcorn epiphysis)

20. Treatment
• Conservative management :
• Mainstay treatment of osteogenesis imperfecta.
• Braces to prevent fractures and contractures.
• Disuse osteopenia weakens the bones, hence immobilisation should
be kept of minimal time required for fracture healing.
• Bisphosphonates
• IV Pamidronate – commonest bisphosphonate used for thr
treatment of osteogenesis imperfecta.
• Active part of the drug binds to the minerals in the bone and
prevent their resorption.
• Dosage : 6-9 mg/Kg body weight/cycle at 4-6 monthly interval for
1.5 to 3 years (have shown reduction in bony pain and reduction in
fractures)
• ADR: flu like symptoms, fever, nausea, vomiting
Seizures, resp distress

21. • Dosage needs to be titrated and decreased after 2 years in
children.
• Pamidroante is excreted for 8 years after caesation of
treatment.
• Monoclonal antibodies:
Denosumab and Bortezomib
Growth hormone therapy
Stem cell therapy
Bone marrow transplantation

22. Surgical management
• Indicated to correct deformities which inhibit function and to
prevent fracture and re-fracture.
• Aim is to restore the anatomical axes of the bones and correct
limb length discrepency and facilitate ambulation by providing
internal splinting to the bones.
• Implants used mainly: Intra-medullary nail, rush nail, elastic
nails, elongating rods.

23. • Sofield Miller Osteotomy:
• Severe deformity of long bones are corrected by multiple
osteotomies followed by realignment by threading the
fragments on an intramedullary nail.

24. • Bailey and Dubow Telescoping medullary rod :
• With growth, the rod elongates and allows the entire length
of the bone to remain re-inforced for several years.
• Rod is anchored into the epiphysis using a T – piece at each
end.

25. • Sheffield expanding IM rod system:
• Realignment osteotomy done through small incisions in order
to preserve the blood supply and periosteal stripping kept to a
minimum.
• Usually done after 18 months of age when the child starts
walking.
• Needs knee arthrotomy for femoral rod insertion and both
knee and ankle arthrotomy for tibial rod insertion.
• Most common complication : Rod migration.

26. • Fassier Duval System :
• Consists of a single proximal entry point and screw in fixation
in the epiphysis without the need of arthrotomy.
• Prevents rod migration unlike sheffield system.
• Ease of insertion.

27. • Basilar invagination causing neurological symptoms is
treated by bony decompression using transoral
approach followed by posterior fusion and posterior
rigid fixation that transfers the weight of the head to
the thoracic spine.
•
• Scoliosis correction is needed If it approaches 45
degrees with the help of posterior spinal fusion with
instrumentation.

28. THANK YOU