May 9, 2024

Osteogenesis imperfecta is a genetic disorder of connective tissue characterized by long bone fractures, skeletal deformities, blue sclera, hearing loss, and fragile opaque teeth (dentigerous imperfect)

  • Autosomal dominant
  • 80-90 % cases:
    • Genetic background reveals a defect in type I collagen formation, which is a major structural protein found in bone and connective tissue



Collagen is derived from the Greek word Kolla (glue) and gennao (to produce) because when boiled it forms glue. The fibrillar collagens, Type I (bone) and Type III are the most abundant in skin. Type I is comprised of polypeptide chains that are arranged in a triple helix. Two of the chains making up Type I collagen are identical (alpha -1 chain ) while the third chain is distinct (alpha-2 chain). Every third amino acid in the collagen molecule is glycine, resulting in Gly-X-Y with X and Y positions occupied by proline and hydroxyproline. Stability is due to disulfide bonds and also cross-links form as a result of the deamination of lysyl and hydroxylysyl residues. Type III collagens are expressed in greater content in scar and healing tissues.


  • Substitution in glycine peptide residue (Gly- X- Y)
  • The affected individual will synthesize abnormal/ineffective residual amounts of collagen
  • If a substitution occurs in the carboxy terminal: More severe consequences


  • No formation of Type I Collagen (defects carries in stop codon)


GradeOI Syndrome NamesTypeSub-typesInheritance
ANon-deforming OI with blue sclera12Both AD
ACommon variable OI with normal sclera47AD and AR
AOI with calcification in Intraosseous membrane51AD
BProgressively deforming OI313AD and AR
BPerinatal lethal OI25AD and AR

Clinical Pictures:

Osteogenesis imperfecta has the following clinical pictures

Multiple fractures with minimal trauma

Fatal: Due to intracranial hemorrhages and respiratory insufficiency (Incompetent rib cage)

Growth arrest (due to microfracture at epiphyseal ends)

Scoliosis or kyphosis

Blue sclera ( Type I, II, and III ) not in Type IV

Poor dentition: Blue, brown, opalescent in color, more prone to caries ( can break easily)

Bruck Syndrome: Multiple joint contracture with bone fragility

Pyridinoline cross-linking deficeincy

Radiographic Finding:

Type I


Olecranon fracture

Type II

Bone shortening, widening, and concentric collapse

Type III

Flattening of metaphysics

Extreme bowing due to multiple fractures

Wormian bone in skull, spine deformity

Protusio acetabuli

Type V

Hyperplastic callus

Intraosseous membrane: Calcification

Laboratory Diagnosis:

Serum calcium and phosphates: Normal

ALP may vary

Confirmative result:

  • Genetic analysis ( COLIA 1, COLIA 2, LEPRE, etc)


Medical Management

  • Pamidronate
    • Bisphosphonates
    • anti-osteoclastic action
    • Cyclic pamidronate (6-9 mg/Kg body weight)
    • Reduces bone pain and fracture rate


  • Asymptomatic hypocalcemia (Tetany)
  • Flu-like syndrome
  • Respiratory distress, Seizures
  • Osteoporosis: Long-term treatment

Other treatment options:

  • Monoclonal antibodies (Denosumab, Bortezomib)
  • Growth hormones
  • Cell therapies (Mesenchymal Stem cells)
  • Bone marrow transplant
  • Induced pluripotent cells
  • Gene therapy

Surgical Management


  • To correct deformities that inhibit functions
  • It prevents fractures and refractures

To restore the anatomical axis of long bone/ correct LLD with the eventual goal of facilitating ambulation and providing an internal splint

If recurrent treatment, bowstring

  • Early surgery indicated
  • Intramedullary rods, double rush nails, TENS, elongating nails

Plates and screws are not used as it causes stress sheilding and fractures occurs at end plates or screw holes

External immobilization is limited as it can cause loss of bone mineral density

In Severe deformities

Multiple osteotomies through metaphyses and shaft of the bone and threading the fragments on the intramedullary rods

When bone is too thin for surgical handling: Replaced with homogenous bone (either bone bank or fibular graft from others)

See also: Skeletal Dysplasia ( Classifications)

See also: Osteopetrosis