Dr. Kevin Yip

Dr Kevin Yip
Orthopaedic Surgeon
MBBS(UK), FRCS(EDIN), FAM(SING), FHKCOS(ORTHO)

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Osteogenesis Imperfecta

Basics
Description
  • OI is a collagen disorder causing osseous fragility.
  • May affect bones, teeth, eyes, hearing, and soft tissue
  • The Sillence classification   is the most widely accepted.
    • Type I: Mild, common form:
      • Fractures occur in later childhood and decrease toward adolescence.
      • Patients with type IA do not have dentinogenesis imperfecta; those with type IB do.
    • Type II: Lethal in the perinatal period
    • Type III : Most severe survivable form
    • Type IV: Moderately severe
    • Type V: Moderately severe, with dislocated radial heads and hyperplastic callus
Pediatric Considerations
  • Types II and III are diagnosed at birth with perinatal death or intrauterine fractures, respectively.
  • Types I and IV may be diagnosed after birth, but generally in early childhood.
  • In the milder forms, the incidence of fractures decreases with age.
Epidemiology
Prevalence
Overall, affects ~1 per 10,000 persons
 
Risk Factors
None, other than heredity
 
Genetics
  • All types have a moderately high rate of spontaneous mutation.
  • Type I: Autosomal dominant with variable penetrance and expressivity
  • Type II: Autosomal recessive or dominant
  • Type III: Autosomal recessive
  • Type IV: Autosomal dominant with variable penetrance and expressivity
  • Type V: Autosomal dominant
Etiology
  • Defects in type I collagen
  • Type I collagen:
    • Is the main collagen in bone matrix
    • Is a triple helix
    • Has glycine as every 3rd amino acid:
      • Substitutions of this amino acid impair coiling of the nonmutated product and exert a dominant negative effect.
Associated Conditions
  • Platybasia, potential brainstem compression
  • Dentinogenesis imperfecta
  • Hypermobile joints with increased incidence of joint dislocation
  • Inguinal, umbilical, and diaphragmatic hernias
Diagnosis
Signs and Symptoms
  • Fragility of bone
  • Short stature
  • Scoliosis, back pain
  • Defective dentinogenesis of deciduous or permanent teeth, or both, resulting in soft, translucent, and brownish teeth
  • Middle-ear deafness
  • Laxity of ligaments, which results in hypermobile joints and potential ankle instability
  • Blue sclerae
  • Skull: Patients may have a widened cranium and small, triangular faces.
  • Increased incidence of musculoskeletal pain in adulthood
  • Symptoms of basilar invagination may include respiratory depression, dyscoordination, spasticity, weakness, contracture, and changes in voice.
Physical Exam
  • OI is diagnosed by fractures of unusual frequency or mechanism.
  • A positive family history and signs such as abnormal dentition, blue sclerae, ligament laxity, scoliosis, or bone bowing/fragility are helpful.
Tests
Lab
  • Cultures of dermal fibroblasts for characterization of type I collagen may be part of the workup; absence of matching may not exclude diagnosis.
  • DNA mutation analysis (blood test) is available through specialized labs.
Imaging
  • Radiography may reveal systemic osteopenia.
  • Other radiographic findings may include long bones with narrow diaphyses and bowing, protrusio acetabuli, vertebral or other fractures, scoliosis, and a concertina femur.
  • Bones are gracile and osteopenic.
  • The pelvis may have a trefoil shape, and protrusio acetabuli is common.
  • The osteopenic vertebrae may fracture easily, resulting in a flattened or biconcave shape; severe scoliosis and kyphosis may develop.
  • The skull may exhibit wormian bones (inclusions in the suture lines).
  • Severe cases: Metaphyses may appear cystic.
Diagnostic Procedures/Surgery
  • Dermal punch biopsy to analyze collagen if routine diagnostic criteria are inconclusive
  • The synthesis and structure of type I collagen produced by the cultured fibroblasts obtained from biopsy then can be analyzed.
  • The mutation can be characterized by specialized lab tests, from DNA in a blood test.
Pathological Findings
  • The bone often appears woven and only occasionally has a normal lamellar pattern.
  • The cortices are thin, and the trabeculae in the metaphyses are markedly attenuated.
  • The collagen fibers of the cornea and skin have a looser arrangement than normal .
Differential Diagnosis
  • Infant with very low birth weight
  • Primary hyperparathyroidism
  • Scurvy
  • Hypophosphatasia
  • Achondrogenesis
  • Chondroectodermal dysplasia
  • Juvenile osteoporosis
  • Nonaccidental injury (child abuse)
  • Congenital syphilis
  • Malignancy (e.g., leukemia)
  • Rickets
  • It may be difficult to discern child abuse from OI .
    • Fractures from child abuse occur most frequently in children <1 year old.
    • Multiple fractures at different stages of healing, posterior rib fractures, and metaphyseal corner fractures are highly specific for nonaccidental injury.
  • A positive family history and signs such as abnormal dentition, blue sclerae, or systemic osteopenia revealed by radiographs may be helpful in the diagnosis of OI.
Treatment
General Measures
  • Treatment depends on the type of OI.
    • Type I may have little impact on the patient.
    • Type II: Lethal perinatal OI:
      • Has some degree of variability
      • In the most severe cases, early death
    • Types III and IV:
      • Greatest therapeutic challenges.
      • Treatment with growth hormone, calcium, and calcitonin has shown little benefit.
  • Diphosphonates treatment (pamidronate, alendronate, etc.) may improve (but will not normalize) bone density, decrease fracture frequency, and improve quality of life in children but not adults.
  • Molecular treatments are a goal for the future.
  • Exercise: A physical therapist should be involved with most children to assess their abilities and plan realistic goals, working to develop ambulatory potential and proceeding with appropriate seating, including a wheelchair if required.
  • Fractures:
    • Usually treated nonoperatively:
      • Fractures heal readily.
      • A fracture is less likely to heal well if substantial angulation develops.
      • Use of lightweight splints or braces may help in getting the child to bear weight quickly.
    • Internal fixation may be used if management by closed treatment proves difficult.
      • Intramedullary fixation is superior to plates and screws because screws tend to dislodge from the weakened bone.
      • A new fracture is more likely to occur at the end of a plate (stress riser effect).
Special Therapy
Physical Therapy
  • Important component of treatment plan:
    • Goals for physical therapy: Muscle and bone strengthening, standing, and ambulation
    • Hydrotherapy for extremities allows active motion and strengthens musculature.
    • Orthotics are an important adjunct.
    • Braces should be lightweight and total contact in design, with joint hinges.
Medication
First Line
Diphosphonates
 
Surgery
  • Anesthesia:
    • Patients with OI are at high risk for many reasons: Restricted neck and jaw mobility, pulmonary function abnormalities from thoracic cage distortion, dentinogenesis imperfecta, and valvular heart disease
    • Avoid anticholinergic agents because they can cause malignant hyperthermia.
  • Osteotomy:
    • At ~5 years of age, corrective osteotomies of larger bones with intramedullary fixation may be performed if indicated.
    • The Bailey-Dubow or Fassier elongating rod diminishes the reoperation rate.
    • Intramedullary nail placement is optimal for children with the potential to stand who have severe bowing or repeated fractures.
    • No absolute rule exists for when intramedullary nail placement should be performed; risk-to-benefit analysis should consider recurrent fracture and deformity versus infection, pain, and the need for nail replacemen.
  • Scoliosis:
    • Curves tend to advance relentlessly; bracing has little effect on deformity progression.
    • New instrumentation methods are changing the approach to scoliosis in OI.
    • Curves may be fused early (at 40°) to halt the relentless progression; this procedure is important in maintaining function and in preventing respiratory complications.
  • A less obvious area of spinal involvement is at the craniocervical junction.
    • Basilar invagination may result and present with neurologic signs resulting from brainstem compression.
    • Once diagnosed, decompression and spinal stabilization are recommended.
Follow-up
Because of multiple potential deformities, patients with OI are best managed in a specialized clinic.

Prognosis
  • Type II disease is lethal perinatally.
  • Type III (next most severe form) patients often require multiple orthopaedic procedures.
  • Types I and IV are milder forms of OI, with type I being the mildest.
  • The fracture rate in all types decreases around puberty.
  • Presenile hearing loss may be the most severe long-term handicap in patients with type I disease.
Complications
A softened base of the skull may lead to platybasia and potential neurologic sequelae.

Patient Monitoring
  • Scoliosis:
    • Patients with OI must be followed closely from an early age to monitor the development and progression of scoliosis.
    • Continue to monitor patients as adults.
  • Neurologic signs: Patients must be followed for neurologic signs of brainstem compression that may be caused by basilar invagination.
Miscellaneous
Codes
ICD9-CM
756.51 Osteogenesis imperfecta
 
Patient Teaching
  • Understanding the necessity of muscle strengthening and ROM exercises is important.
  • Family members must monitor the skin around braces and casts.
  • They must also try to recognize when fractures occur and be compliant with frequent follow-up.
FAQ
Q: Does exercise improve bone density in OI?
A: It improves it, but not to a normal degree.
 
Q: When, if ever, should patients with OI be treated with intramedullary nails?
A: If they have repeated fractures, the bowing interferes with function, and the age and size allows durable correction. Some patients have such severe OI that surgery is not successful.

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