- Characterized by bone fragility, ligamentous laxity and joint hypermobility
- 87% of cases are caused by a defect in type I collagen
- High variability in the severity of the disorder
- Must be differentiated from non-accidental trauma
- Bisphosphonates are utilized for medical management
- Intramedullary fixation is favored for operative treatment of fractures
Description:Osteogenesis Imperfecta (OI) encompasses a group of disorders characterized by a varying degree of bone fragility and frequent fractures often leading to limb bowing or other deformities. The most widely used clinical classification is the Sillence classification, which originally included four groups (Sillence, 1979). (Table 1)
|Type I||Dominantly Inherited OI with blue sclerae|
|Type II||Lethal perinatal OI with radiographically crumpled femora and beaded ribs|
|Type III||Progressively deforming OI|
|Type IV||Dominantly inherited OI with normal sclerae|
A subsequent expansion of the classification added an additional 3 groups (Rauch,
2004). As additional genetic causes were identified, the number of subtypes gradually increased up to OI type XIV (Forlino, 2011).
In 2009, the International Nomenclature group for Constitutional Disorders ICHG of the Skeleton decided to use a phenotypic basis to group the existing OI syndromes into 5 types, utilizing the original 4 types with a type 5 representing OI with calcification in the interosseous membranes (Warman, 2011). (Table 2) The new nomenclature transitioned to Arabic numerals from Roman numerals which had implied a distinct genetic locus.
|Mild to Moderate Severity|
|Type 1||Non-deforming OI with blue sclerae|
|Type 4||Common variable OI with normal sclerae|
|Type 5||OI with calcification in interosseous membranes|
|Progressively Deforming and Perinatally Lethal|
|Type 3||Progressively deforming OI|
|Type 2||Perinatally lethal OI|
Epidemiology:OI affects approximately one in 10,000 births. There is no racial or ethnic predisposition (Roughley, 2003). In type I, the annual fracture rate appears to be less than or equal to 1, while the pre-pubertal rates of fracture in more severe types are likely to be greater than 3 annually (Van Dijk, 2014). Type I accounts for 50% of cases in Europe and the US (Steiner, 2017).
Clinical Findings:Children with type I are on the milder end of the spectrum. The dominant clinical features are blue sclerae with or without involvement of the teeth, known as dentinogenesis imperfecta. Often this is referred to as “non-deforming OI” as bowing and deformity is less common.
The most severe cases of the condition are found in type II where children experience multiple prenatal fractures. This type is often lethal in the perinatal period.
Type III is the most severe form that is routinely compatible with life. Children affected often have severe growth retardation and depend on a wheelchair for mobility. Osteopenia leads to multiple fractures and progressive bowing. (Figure X) Teeth and sclerae appear to be unaffected. Osteopenia, ligamentous laxity and compression deformity of the vertebral bodies may lead to thoracolumbar scoliosis. Basilar invagination may also be present.
In Type IV, there is bone fragility of a more severe degree then in type I but less severe than type III, most often with normal sclerae. Involvement of the teeth may be present.
A severity grading scale has been proposed which utilizes clinical data, frequency of fractures, bone densitometry, and mobility (Van Dijk, 2014). (Table 3)
OI is a disorder of connective tissue and those children affected may also exhibit associated hearing loss (up to 40% in type I), decreased pulmonary function, skin fragility, valvular regurgitation, and joint hyperlaxity (Bonita, 2010; LoMauro, 2012).
Children who present with isolated olecranon apophyseal fractures should be evaluated for OI given its incidence in this group.
Imaging Studies:OI may be identified by prenatal ultrasonography. (Table 3) In severe forms of the disease, characteristic radiographic findings include generalized osteopenia, with bowing deformities of the limbs. There may be multiple fractures at different stages of healing. Joints are not involved. Children with less severe OI often present a greater diagnostic challenge as plain radiographs will not reveal the diagnosis.
Children with OI do not require imaging for every presumed fracture. In the absence of instability or deformity, empiric treatment without imaging is reasonable. Additionally, follow-up radiographs for inherently stable injuries again is not required. Dual-energy x-ray absorptiometry (DEXA) bone density can provide diagnostic information and guide treatment (Huang, 2007).
Treatment:A multidisciplinary approach to OI is preferred. This should include physical therapy, medical management, and orthopedic considerations. The goal in treatment is for improvement of independent mobility, pain control and fracture prevention and management. Therapy can help to mobilize joints, improve strength and aerobic conditioning and allow for greater independence in ambulation as well as guide treatment with bracing or ambulatory aids (Brussel, 2008; Montpetit, 2015).
Bisphosphonates act as specific inhibitors to osteoclast-mediated bone resorption and have been widely utilized in these children. In a recent Cochrane review of fourteen studies, bisphosphonates were shown to improve bone density after treatment (Dwan, 2016). This increase in bone density has decreased the number of clinical fractures (Gatti, 2004).
Most fractures in OI children may be treated nonoperatively. Fracture healing is unaffected in patients with OI and therefore the duration of immobilization should not be extended. General treatment guidelines are similar to those of other children, although intramedullary fixation is used whenever possible instead of plate fixation (Fassier, 2014). Operative treatment of limb deformity as well as prophylactic treatment should be done with intramedullary fixation. Growing, telescoping implants are most commonly used to allow for longer-term prophylaxis. Scoliosis should be treated early to help prevent respiratory complications from progressive, severe deformity. Growing rod instrumentation is a consideration for progressive early onset scoliosis.
Complications:Side effects of bisphosphonate use include atypical femur fractures, delayed healing of osteotomies as well as hypocalcemia, vomiting, fever or even respiratory depression during the first dose of the intravenous forms (Kumar, 2016; Munns, 2004; Vasanwala, 2016)
Surgical complications arise from poor implant choice or can arise from the implants themselves. Plates leave stress risers in weak bone leading to repeat fractures. Migration, extrusion, and implant failure are common for telescoping and traditional intramedullary implants (Zionts, 2014).
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Top Contributors:Holly Leshikar MD
Jeff Martus MD