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
Pathophysiology
Collagen
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.
Qualitative
- 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
Quantitative
- No formation of Type I Collagen (defects carries in stop codon)
Classification
| Grade | OI Syndrome Names | Type | Sub-types | Inheritance |
| A | Non-deforming OI with blue sclera | 1 | 2 | Both AD |
| A | Common variable OI with normal sclera | 4 | 7 | AD and AR |
| A | OI with calcification in Intraosseous membrane | 5 | 1 | AD |
| B | Progressively deforming OI | 3 | 13 | AD and AR |
| B | Perinatal lethal OI | 2 | 5 | AD 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
Osteopenia
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)
Management:
Medical Management
- Pamidronate
- Bisphosphonates
- anti-osteoclastic action
- Cyclic pamidronate (6-9 mg/Kg body weight)
- Reduces bone pain and fracture rate
Complications:
- 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
Aim
- 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
