Osteogenesis Imperfecta

- See: Pyknodyostosis

- Discussion:
    - disease characterized by failure of maturation and organization of collagen fibers;
          - defect in collagen (procollagen to type I collagen sequence and abnormal cross linking) leading to decreased collagen secretion,
                    bone fragility;
          - there may be an inability to form normal bone due to a defect in osteoblastic function;
    - with the formation of abnormal bone, there is a secondary, though not precisely understood, increase in resorption of bone with a
                    secondary increase in bone turnover;
    - osteoid mineralization, osteoclastic activity, and intramembranous bone formation are not affected;
    - classification of osteogenesis imperfecta:
          - note that there is a wide variety in the OI phenotype, but all share in osseous fragility and propensity for fracture;
    - diff dx:
          - juvenile osteoporosis
          - rickets
          - battered child syndrome
          - leukemia;
          - abundant frx callus may be mistaken for osteosarcoma;
    - references:
          - Distinct biochemical phenotypes predict clinical severity in nonlethal variants of osteogenesis imperfecta.  
          - Studies of collagen synthesis and structure in the differentiation of child abuse from osteogenesis imperfecta.      

- Clinical Features:
    - short stature, scoliosis, tooth defects, hearing defects, propensity for fractures, and ligamentous laxity;
          - other abnormalities associated with abnormal collagen formation are evident, such as blue sclerae, abnormalities of tooth
                    formation and skull shape, and occasional deafness;
    - fractures:
          - results from marked loss of bone and leads to significant lack of growth of bone in length, and multiple deformities secondary
                    to these fractures;
          - femur fractures are most common but tibial frx may show most severe angulation;
          - frxs may occur at any age, but frx occurance frequently decreases as age increases (often fractures cease at puberty);
          - some adults affected with this disorder will only give a history of occassional fractures and mild osteopenia;
          - fractures tend to heal readily w/ exuberant callus, but the callus formed is of poor quality (identical in structure with the rest of
                  the skeleton);
                  - hence it is easily deformed by forces associated with wt bearing; 
          - ref: Fractures at Diagnosis in Infants and Children With Osteogenesis Imperfecta
    - joints:
          - laxity of the ligaments results in hypermobile joints & increased incidence in joint dislocation;
    - hearing:
          - hearing defects 2nd to inner and middle ear abnormalities may develop, & affected children require regular audiologic 
    - pelvis:
          - protrusio acetabuli may occur in type III and may narrow pelvic outlet, and can cause constipation or even partial obstruction of
                   rectosigmoid colon;

- Radiographs:
    - bones are gracile and diffusely osteopenic, w/ thin cortices & attenuated trabecular pattern;
    - note that w/ some OI phenotypes, radiographic osteopenia may be slight and may be missed on x-ray; (in these cases, consider
           dual energy x-ray absorptiometry);
    - references:
           - The role of dual energy x-ray absorptiometry in aiding the diagnosis of pediatric osteogenesis imperfecta.


- Treatment:
    - Sofield osteotomy:
          - indicated for OI patients w/ repetitive frx or progressive angular deformity in a weightbearing bone;
          - involves multiple realignment osteotomies and internal fixation with a load sharing IM device is the treatment of choice;
          - reference:
                - The Sofield-Millar operation in osteogenesis imperfecta  A modified technique
                            - bone grafting is not required for fracture healing, and compression plating predisposes to further fracture;
    - bone deformities caused by microfrx on tension side are common;
          - when severe enough to interfere with bracing or allow recurrent frx, multiple realignment osteotomies (Sofield), fixed w/
                   expandable IM rods is performed;
          - note that these patients may be at risk for malignant hyperthermia;
          - all substantial deformities should be corrected simultaneously to limit immobilization time;
          - postop bracing to avoid recurrent deformity must be considered;

- Spine:
    - cervical spine:
          - basilar impression may occur in up to 25% of patients (more common w/ type IV);
          - MRI is radiographic study of choice;
    - thoraco-lumbar spine:
          - scoliosis develops in over 50% of involved patients;
          - bracing is ineffective because of the plasticity of the chest wall;
          - surgical correction w/ posterior instrumentation is usually successful;
                  - bone fragility may complicate surgical fixation;
                  - hooks may be reinforced with methylmethacrylate;
                  - segmental instrumentation techniques have been used successfully;
          - vertebral compression of fractures caused by osteoporosis can occur at any age and may lead to symptomatic back deformities;
          - references:
                  - The operative management of basilar impression in osteogenesis imperfecta. 
                  - The spine in osteogenesis imperfecta.
                  - Osteogenesis imperfecta. Radiographic classification, natural history, and treatment of spinal deformities.


Non-union of fractures in children who have osteogenesis imperfecta.

Defective association between collagen fibrils and proteoglycans in fragile bone of osteogenesis imperfecta.

Aftermath of osteogenesis imperfecta: the disease in adulthood.

Hip and knee replacement in osteogenesis imperfecta.

Microvascular and cellular defects of the periosteum of osteogenesis imperfecta.

Gastrointestinal problems in patients who have type-III osteogenesis imperfecta.

Intramedullary rodding with Bailey-Dubow extensible rods in osteogenesis imperfecta: an interim report of reports and complications

Fractures in childhood: osteogenesis imperfecta or child abuse? 

Functional Significance of Bone Density Measurements in Children with Osteogenesis Imperfecta.

Deficiency of Cartilage-Associated Protein in Recessive Lethal Osteogenesis Imperfecta.

Intravenous Pamidronate Therapy in Osteogenesis Imperfecta: Response to Treatment and Factors Influencing Outcome.

Successful results of pamidronate treatment in children with osteogenesis imperfecta with emphasis on the interpretation of bone mineral density for local standards.

Original Text by Clifford R. Wheeless, III, MD.

Last updated by Data Trace Staff on Friday, July 8, 2016 10:33 am