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