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Updated: Nov 3 2022

Osteogenesis Imperfecta

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Images
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https://upload.orthobullets.com/topic/4102/images/wormian.jpg
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https://upload.orthobullets.com/topic/4102/images/saber shin photo_moved.jpg
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  • summary
    • Osteogenesis Imperfecta is a common congenital disorder caused by a mutation in COL1A1 or COL1A2 genes resulting in abnormal collagen cross-linking and overall decrease in type 1 collagen. Patients present with fragility fractures, scoliosis, hearing loss, and cardiovascular abnormalities. 
    • Diagnosis is made based on family history associated with typical radiographic and clinical features. No commercially available diagnostic test exists due to the variety of genetic mutations.
    • Treatment is a multidisciplinary approach for fracture prevention with bisphosphonates, fracture management when present, and realignment osteotomies for long bone deformities.
  • Etiology
    • Pathophysiology
      • can result from
        • decreased collagen secretion
        • production of abnormal collagen
      • leads to insufficient osteoid production
        • physeal osteoblasts cannot form sufficient osteoid
        • periosteal osteoblasts cannot form sufficient osteoid and therefore cannot remodel normally
    • Genetics
      • 90% have an identifiable genetic mutation
        • COL 1A1 and COL 1A2
          • causes abnormal collagen cross-linking via a glycine substitution in the procollagen molecule
      • autosomal dominant and autosomal recessive forms
        • milder autosomal dominant forms (Types I and IV)
        • severe autosomal dominant forms (Types II and III)
        • autosomal recessive forms (Type VI, VII)
      • CRTAP and LEPRE1 genes associated with severe, lethal forms of OI not associated with primary structural defect of type I collagen
    • Orthopaedic manifestations
      • bone fragility and fractures
        • fractures heal in normal fashion initially but the bone does not remodel
        • can lead to progressive bowing
      • ligamentous laxity
      • short stature
      • scoliosis
      • codfish vertebrae (compression fx)
      • basilar invagination
      • olecranon apophyseal avulsion fx
        • most common first presenting sign 
      • coxa vara (10%)
      • congenital anterolateral radial head dislocations
    • Non-Orthopaedic manifestations
      • blue sclera
      • dysmorphic, triangle shaped facies
      • hearing loss
        • 50% of adults with OI
        • may be conductive, sensorial and mixed
      • brownish opalescent teeth (dentinogenesis imperfecta)
        • alteration in dentin
        • brown/blue teeth, soft, translucent, prone to cavities
        • affects primary teeth > secondary teeth
      • wormian skull bones (puzzle piece intrasutural skull bones)
      • hypermetabolism
        • increased risk of malignant hyperthermia
        • hyperhidrosis, tachycardia, tachypnoea, heat intolerance
      • thin skin prone to subcutaneous hemorrhage
      • cardiovascular
        • mitral valve prolapse
        • aortic regurgitation
  • Anatomy
    • Type I collagen is the most important structural protein of bone, skin, tendon, dentin, sclera
    • triple helix structure
      • two alpha-1 chains coded by genes COL1A1
      • one alpha-2 chain coded by gene COL1A2
      • triple helix structure is possible because of glycine at every 3rd amino acid residue
        • genetic mutations alter triple helix by substitution of glycine with another amino acid
  • Classification
    • Sillence originally classified into four types
      • however most likely a continuum of disease
      • additional types have been added
      • 90% of patients can be grouped into the Sillence Type I and IV
      • Sillence Classification of Osteogenesis Imperfecta (simplified)
      • Type
      • Inheritance
      • Sclera
      • Features
      • Type I
      • Autosomal dominant
      •  Quantitative disorder in collagen
      • Blue
      • Mildest form.
      • Presents at preschool age (tarda).
      • Hearing deficit in 50%
      • Divided into type A and B based on tooth involvement
      • Type II
      • Autosomal dominant
      • Qualitative disorder in collagen
      • Blue
      • Lethal in perinatal period
      • Type III
      • Autosomal dominant
      • Qualitative disorder in collagen
      • Normal
      • Most severe survivable form
      • Fractures at birth.
      • Progressively short stature.
      • Type IV
      • Autosomal dominant
      • Qualitative disorder in collagen
      • Normal
      • Moderate severity.
      • Bowing bones and vertebral fractures are common.
      • Hearing normal.
      • Divided into type A and B based on tooth involvement
      • Sillence Classification modification (Types V-VII added)
      • These 3 types of OI have no Type I collagen mutation but have abnormal bone on microscopy and a similar phenotype
      • Congenital anterolateral radial head dislocation
      • Hypertrophic callus after a fracture
      • Ossification of IOM between radius and ulna and tibia and fibula
      • Autosomal Dominant
      • Type VI
      • Moderate severity
      • Similar to type IV
      • Autosomal recessive
      • Type VII
      • Associated with rhizomelia and coxa vara
      • Autosomal recessive
  • Presentation
    • Symptoms
      • mild cases
        • multiple fractures during childhood
      • severe cases
        • present with fractures at birth and can be fatal
        • number of fractures typically decreases as patient ages and usually stops after puberty
      • basilar invagination
        • presents with apnea, altered consciousness, ataxia, or myelopathy
        • usually in third or fourth decade of life, but can be as early as teenage years
    • Physical exam
      • multiple fractures leads to
        • saber shin appearance of tibia
        • bowing of long bones
      • trendelenburg gait
        • if coxa vara present
  • Imaging
    • Radiographs
      • thin cortices
      • generalized osteopenia
      • saber shins
      • skull radiographs reveal wormian bones
      • coxa vara
  • Evaluation
    • Labroratory
      • mildly elevated ALP
    • Histology
      • increased diameter of haversion canals and osteocyte lacunae
      • replicated cement lines
      • increased number of osteoblasts and osteoclasts
      • decreased number of trabeculae
      • decreased cortical thickness
    • Diagnosis
      • diagnosis is based on family history associated with typical radiographic and clinical features
      • Labs
        • no commercially available diagnostic test due to variety of genetic mutations
        • laboratory values are typically within normal range
      • possible methods diagnosis include
        • skull radiographs to look for wormian bones
        • fibroblast culturing to analyze type I collagen (positive in 80% of type IV)
          • can be used for confirmation of diagnosis in equivocal cases
        • biopsy
          • collagen analysis of a punch biopsy
          • iliac crest biopsy which shows a decrease in cortical widths and cancellous bone volume, with increased bone remodeling.
  • Treatment of Fractures
    • Fracture prevention
      • early bracing
        • indicated to decrease deformity and lessen fractures
      • bisphosphonates
        • indicated in most cases of OI to reduce fracture rate, pain, improve ambulation
          • marked improvement in pain at 1-6wk after initiation
        • inhibits osteoclasts
          • increases cortical diameter 88%
          • increases cancellous bone volume 46%
        • does not affect development of scoliosis
        • chronic use causes horizontal metaphyseal bands seen on radiographs
          • growth arrest lines
        • maintain bisphosphonate-free period around the time of IM rodding
          • interferes with osteotomy healing >> fracture healing
      • growth hormone
      • bone marrow transplantation
        • has been used with some success
    • Fracture treatment
      • nonoperative
        • observation
          • indications
            • indicated if child is <2 years (treat as child without OI)
      • operative
        • fixation with telescoping rods
          • indications
            • consider in patients > 2 years
            • allow continued growth
        • fixation with load sharing device
          • indications
            • consider in patients > 2 years
            • fracture with deformity beyond accepted tolerances after closed reduction
  • Treatment of Long Bone Bowing Deformities
    • Operative
      • realignment osteotomy with rod fixation (Sofield-Miller procedure)
        • indications
          • severe deformity to reduce fracture rates
        • techniques include
          • nontelescopic devices (Rush rods, Williams rods)
          • telescopic devices (Sheffield rod, Bailey-Dubow rod, Fassier-Duval rod)
  • Treatment of Scoliosis
    • Vital capacity drops to 40% of expected for a 60° curve
    • Nonoperative
      • observation
        • indications
          • if curve is <45 °
      • bracing is ineffective and not recommended
        • because of fragility of ribs
    • Operative
      • posterior spinal fusion
        • indications
          • for curves > 45 ° in mild forms and > 35 ° in severe forms
        • technique
          • challenging due to fragility of bones
          • use allograft instead of iliac crest autograft due to paucity of bone
          • ASF only indicated in very young children to prevent crankshaft
          • associated with a large blood loss
  • Treatment of Basilar Invagination
    • Operative
      • decompression and posterior fusion
        • indications
          • radiographic features of invagination and cord compression with physical exam findings of myelopathy
        • techniques
          • resection of bony compression via transoral approach
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