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Osteogenesis imperfecta
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Osteogenesis imperfecta

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  • 1.  OI is one of the most common skeletal dysplasias. It is a generalized disease of connective tissue  In 1835, Lobstein coined the term osteogenesis imperfecta and was one of the first to correctly understand the etiology of the condition.  Other names for OI are Lobstein disease, brittle-bone disease, blue-sclera syndrome, and fragile-bone disease.
  • 2. Pathophysiology  In OI, pathologic changes are seen in all tissues with type 1 collagen. The basic defect is one of a qualitative or quantitative reduction in type 1 collagen.  Most cases of OI, are now known to arise from autosomal dominant mutations.  The disease affects both endochondral and intramembranous ossification.
  • 3.  Quantitative defects : a mild form . The numbers of osteoclasts and osteocytes are normal. Bone trabeculae are thin and disorganized. Lamellar bone is seen in the diaphysis and metaphysis Qualitative defects: a severe form of the disease occurs. There is reduced cortical bone thickness, lack of normal cortical bone formation, and disorganization of the growth plate. Woven bone is seen, with minimal osteoid bone and no lamellar bone
  • 4. Etiology  In OI due to quantitative defects of type 1 collagen, mutations are usually found on the COL1A gene.  In OI due to qualitative defects of type 1 collagen, autosomal dominant mutations are found on either the COL1A or the COL1B gene  The mutations result in the production of a mixture of normal and mutant collagen chains  The type 1 collagen thus formed is functionally impaired because of the mutant chain
  • 5. Epidemiology  The overall incidence of OI is approximately 1 case for every 20,000 live births  OI can present at any age, although the age when symptoms (ie, fractures) begin varies widely  OI is equally common in males and females. The disease appears to have no predilection for a particular race.
  • 6. Clinical presentation  Blue sclerae  Triangular facies  Macrocephaly  Hearing loss  Defective dentition  Barrel chest  Scoliosis  Limb deformities  Fractures  Joint laxity  Growth retardation
  • 7. OI classification & Characteristics  Most widely used classification is that of Sillence which defines four clinical types  Type I-IV  Recently added 3 more classifications (V-VIII)  Causes unknown
  • 8. Type 1 OI  Most common & mildest form  Collagen is of normal quality but is produced in insufficient quantities  Bone fractures are common during childhood & adolescence from minor trauma (fractures less frequent during adulthood)  Normal or near-normal stature  Loose joints and muscle weakness
  • 9.  Sclera usually have a blue, purple, or gray tint  Tendency toward spinal curvature  Bone deformity absent or minimal  Brittle teeth possible  Hearing loss possible (early 20s or 30s)  Normal life expectancy
  • 10. Type 2 OI  Most severe form  Collagen is not of a sufficient quality or quantity  Frequently lethal at or shortly after birth, often due to respiratory problems.  Numerous fractures and severe bone deformity.  Small stature with underdeveloped lungs.  Usually still-birth or dies shortly after birth
  • 11. Type 3 OI (progressive)  Collagen quantity is sufficient but is not of a high enough quality  Bones fracture easily, sometimes even before birth  Bone deformity, often severe  Respiratory problems possible  Short stature, spinal curvature and barrel-shaped rib cage  Loose joints  Poor muscle tone in arms and legs  Discoloration of the sclera  Early loss of hearing  Life expectancy shorter than normal
  • 12. Type 4 OI  Collagen quantity is sufficient but is not of a high enough quality  Between Type I and Type III in severity  Bones fracture easily, especially before puberty  Short stature, spinal curvature and barrel-shaped rib cage  Bone deformity is mild to moderate  Discoloration of the sclera (whites of the eyes)  Early loss of hearing  Normal life expectancy
  • 13. Type 5 OI  Type V OI is an autosomal dominant condition with a severity similar to that of type IV disease but a predisposition to hyperplastic callus formation.  Characteristic features include ossification of the interosseous membrane of the forearms and legs, leading to limited pronation and supination and a radiopaque metaphyseal band in growing patients.
  • 14. Type VI  OI type VI is clinically similar to types II and IV, but it has distinctive histology, including hyperosteoid bone due to a mineralization defect, and does not have a disturbance of bone mineral metabolism. Type VII  OI type VII has been described in an isolated First Nations community in northern Quebec.It is clinically similar to OI types II and IV but has rhizomelia as a distinctive feature.
  • 15. Differential Diagnoses  Achondroplasia  Glucocorticoid Therapy and Cushing Syndrome  Homocystinuria/Homocysteinemia  McCune-Albright Syndrome  Osteopetrosis  Osteoporosis  Rickets  Scurvy  Wilson Disease
  • 16. Investigations Plain Radiography  Obtain a radiographic skeletal survey after birth. Plain radiographs may depict the following 3 radiologic categories of OI:  Category I – Thin and gracile bones  Category II – Short and thick limbs  Category III – Cystic changes
  • 17.  Fractures – Commonly, transverse fractures and those affecting the lower limbs  Excessive callus formation and popcorn bones - Multiple scalloped, radiolucent areas with radiodense rims
  • 18.  Skull changes - Wormian bones, enlargement of frontal and mastoid sinuses, and platybasia with or without basilar impression
  • 19.  Deformities of the thoracic cage - Fractured and beaded ribs; and pectus carinatum  Pelvic and proximal femoral changes - Narrow pelvis, compression fractures, protrusio acetabuli, and shepherd’s-crook deformities of the femurs
  • 20. Densitometry  Dual x-ray absorptiometry (DEXA) may be used to assess bone mineral density in children with milder forms of OI. Bone mineral density, as measured with DEXA, is low in children and adults with OI regardless of severity.  CT densitometric bone scanning may be helpful in atypical cases of OI, though normal bone density does not exclude mild forms of the disease.
  • 21.  Polarized light microscopy or microradiography may be used in combination with scanning electron microscopy to assess dentinogenesis imperfecta.  Skin biopsy, collagen can be isolated from cultured fibroblasts and assessed for defects, with an accuracy of 85-87%.  Bone biopsy may show changes in the concentrations of noncollagenous bone proteins, such as osteonectin, sialoprotein, and decorin.
  • 22. Collagen synthesis analysis  Sodium dodecyl sulfate–polyacrylamide gel electrophoresis (SDS-PAGE)  2-Dimensional SDS-PAGE  Cyanogen bromide (CNBr) mapping  Thermal stability studies An analysis of the amino acid composition of collagens may be useful.
  • 23. Prenatal testing  Prenatal DNA mutation analysis can be performed in pregnancies with risk of OI to analyze uncultured chorionic villus cells.  Prenatal ultrasonography is most useful in evaluating OI types II and III. It is capable of detecting limb- length abnormalities at 15-18 weeks’ gestation. In its most severe form, the disease may be evident as early as 16 weeks’ gestation.
  • 24. Treatment-General  NO CURE  Care for broken bones & brittle teeth  Pain medication  Physical therapy  Use of orthotics, wheelchairs, braces, and other aids  Surgery remains a pillar of treatment for patients with OI
  • 25. Treatment-Specific  Bisphosphonates (BPs)  Analogues of inorganic pyrophosphate and act by binding to hydroxyapatite in bone matrix, thereby inhibiting the dissolution of crystals. They prevent osteoclast attachment to the bone matrix and osteoclast recruitment and viability.  Increase bone mass and reduce the incidence of fracture  Administered orally or by IV  Pamidronate, risedronate, alendronate,
  • 26.  Surgery  Insert metal rods (rodding) in long bones to improve strength  Because the bone is soft in OI, rods (eg, extendable Sheffield rods or Bailey-Dubow rods), pins (eg, Rush pins), and wires (eg, Kirschner wires) are used rather than solid nails, plates, and screws  Osteotomies should be simple, preferably single, and performed under direct vision with maximum care and gentle handling of tissues.
  • 27.  Surgery for basilar impression  Best treated with decompression and stabilization of the craniocervical junction. This procedure is reserved for cases with neurologic deficiencies.  Surgery for spinal deformities  Surgery is indicated when the following 2 conditions are present: Acceptable bone quality Progressive scoliosis with curvature of more than 45° if OI is mild or more than 30-35° if OI is severe  Posterior spinal arthrodesis is the treatment of choice and is best performed with segmental instrumentation.
  • 28.  Physiotherapy (or hydrotherapy)  strengthen muscles and improve mobility in a gentle manner  Physiotherapy has become more effective in the postbisphosphonate era because of the decrease in bone fragility and the improved prognosis for standing or walking  Weightbearing is promoted in the pool, on tricycles, and with walkers. Prone positioning is used to prevent hip flexion contractures
  • 29. People with OI
  • 30. THANK YOU