Basics
Description
- Inherited abnormality ofprocollagen amino acid sequence
- Bone hypomineralization and incomplete ossification result in brittle bones.
- Abnormal collagen affects all connective tissue to varying degrees.
- Time course is variable:
- Most cases involve fractures during childhood followed by quiescence during adolescence and early adulthood.
Etiology
- Procollagen defects result in abnormalities of bone and connective tissue matrix.
- Defects in different sites on procollagen protein chain result in more severe forms.
- Defects are inherited, either autosomal recessive (generally milder) or autosomal dominant (more severe).
- Lethal cases involve sporadic or new mutations.
- Ehlers " “Danlos syndrome involves mutations of the same procollagen protein in different locations.
- Most cases involve pathologic fractures during childhood.
- Multiple fractures often initiate evaluation for abuse, but the possibility of pathologic fractures also should be considered.
Diagnosis
Signs and Symptoms
- Multiple heritable defects that lead to brittle bones:
- Often associated with other connective tissue abnormalities
- A suspected fracture with a relatively minor mechanism or a history of multiple fractures in a child suggests the diagnosis.
- Careful social history with consideration for the possibility of nonaccidental trauma
- Bones:
- Multiple recurrent fractures (especially in long bones) are the hallmark of this disease.
- Fractures may be present at birth or may recur in the elderly.
- Shortened or bowed limbs, pectus excavatum, curving of long bones, vertebral compression fractures, scoliosis, kyphosis, and abnormal skull shape
- All bones are affected to some extent (see Imaging/Special Tests).
- Eyes:
- Blue sclerae are another hallmark of this disease.
- No visual changes are reported.
- Ears:
- Hearing loss usually begins in adolescence; >90% of patients have some deficit by age 30 yr.
- Hearing loss is generally sensorineural, although some middle ear abnormalities have been demonstrated.
- Academic difficulties should raise suspicion of possible hearing deficits.
- Other:
- Discolored, fragile, and abnormal shape of teeth
- Shares several features with Ehlers " “Danlos syndrome:
- Loose joints
- Valve problems
- Vascular abnormalities
- Thyroid abnormalities may be seen.
- Extreme cases may result in perinatal death.
Essential Workup
- Diagnosis is usually made as combination of clinical and radiographic findings.
- History of repeated fractures or fractures with unimpressive mechanism
- Thorough search for other tender areas and evaluation of eyes, teeth, and joints is important for diagnosis.
- Careful exam of neurovascular status distal to fracture
Diagnosis Tests & Interpretation
Lab
- Evaluate for metabolic derangements such as hyperparathyroidism, vitamin C or D deficiencies, and calcium/phosphate abnormalities.
- DNA studies may be indicated for familial analysis, prenatal testing, and genetic counseling.
- Tissue biopsy is controversial but may help differentiate from tumors.
Imaging
- Radiographs of fracture sites:
- May reveal osteopenia (usually mild)
- Crumpled long bones ( "accordion femora " ť)
- Incomplete ossification at physes
- Skeletal survey is mandatory, especially in children.
- Skull films may show wormian appearance of irregular ossification.
- Popcorn-like deposits on long-bone ends are poor prognostic finding.
- Formal audiologic testing as outpatient is required in older patients.
Differential Diagnosis
- Nonaccidental trauma in children
- Ehlers " “Danlos syndrome
- Hypophosphatasia
- Achondroplasia
- Scurvy
- Congenital syphilis
- Celiac disease
Treatment
Pre-Hospital
Personnel should obtain information about mechanism or social factors that point toward pathologic fracture vs. nonaccidental trauma. ‚
Initial Stabilization/Therapy
- Airway management and resuscitation as indicated
- Fracture immobilization/splinting
Ed Treatment/Procedures
- Specific fracture management dictated by type and location of injury
- Orthopedic consultation regarding need for traction or operative fixation
- No specific treatment for osteogenesis imperfecta exists at present.
Medication
- Pain medications as indicated
- Elderly women may benefit from calcium (1 " “1.5 g/d) and estrogen replacement (0.625 mg/d).
Follow-Up
Disposition
Admission Criteria
- Admission is determined by multiple trauma or operative needs for fracture repair.
- Pediatric patients may need admission to investigate possibility of nonaccidental trauma.
Discharge Criteria
- Patients may be considered for outpatient management if isolated fracture is present and appropriate home resources are available.
- Most patients should be discharged with orthopedic and primary physician follow-up.
Issues for Referral
- Orthopedic referral is driven by the acute injury.
- The presence of fractures in multiple locations or at different times also suggests nonaccidental trauma, which should prompt acute consultation and/or referral per local protocol.
Follow-Up Recommendations
- Follow-up is generally driven by the acute injuries.
- Follow-up with the primary physician should be instituted to encourage treatment and monitoring of the disease.
Pearls and Pitfalls
- The most challenging aspect of caring for these patients is differentiating between pathologic fractures associated with osteogenesis imperfecta and nonaccidental trauma. With any questions, acute consultation and/or referral should be initiated per local protocol.
- It is a myth that children with osteogenesis imperfecta feel less pain than other patients.
- Predisposition to respiratory infections
Additional Reading
- Bishop ‚ N. Osteogenesis imperfecta. Medicine. 2005;33(12):67 " “69.
- Prockop ‚ DJ. Heritable disorders of connective tissue. In: Wilson ‚ JD, et al., eds. Harrisons Principles of Internal Medicine. 12th ed. New York, NY: McGraw-Hill; 1991:1860.
- Rauch ‚ F, Glorieux ‚ FH. Osteogenesis imperfecta. Lancet. 2004;363(9418):1377 " “1385.
- Shapiro ‚ JR, Sponsellor ‚ PD. Osteogenesis imperfecta: Questions and answers. Curr Opin Pediatr. 2009;21(6):709 " “716. www.oif.org
See Also (Topic, Algorithm, Electronic Media Element)
Specific Orthopedic Injuries ‚
Codes
ICD9
756.51 Osteogenesis imperfecta ‚
ICD10
Q78.0 Osteogenesis imperfecta ‚
SNOMED
- 78314001 Osteogenesis imperfecta (disorder)
- 385482004 osteogenesis imperfecta type I (disorder)