Elsevier

The Lancet

Volume 363, Issue 9418, 24 April 2004, Pages 1377-1385
The Lancet

Seminar
Osteogenesis imperfecta

https://doi.org/10.1016/S0140-6736(04)16051-0Get rights and content

Summary

Osteogenesis imperfecta is a genetic disorder of increased bone fragility, low bone mass, and other connective-tissue manifestations. The most frequently used classification outlines four clinical types, which we have expanded to seven distinct types. In most patients the disorder is caused by mutations in one of the two genes encoding collagen type 1, but in some individuals no such mutations are detectable. The most important therapeutic advance is the introduction of bisphosphonate treatment for moderate to severe forms of osteogenesis imperfecta. However, at present, the best treatment regimen and the long-term outcomes of bisphosphonate therapy are unknown. Although this treatment does not constitute a cure, it is an adjunct to physiotherapy, rehabilitation, and orthopaedic care. Gene-based therapy presently remains in the early stages of preclinical research.

Section snippets

Diagnosis

The clinical diagnosis of osteogenesis imperfecta is based mainly on the signs and symptoms outlined above. Traditionally, much emphasis has been laid on the presence or absence of blue sclera and dentinogenesis imperfecta as diagnostic signs of osteogenesis imperfecta. This practice still holds true, but some limitations should be recognised. Dark or bluish sclerae are very typical in healthy infants, and therefore this finding is not of much diagnostic use in this age-group. Dentinogenesis

Pathogenesis

This section focuses on forms of osteogenesis imperfecta that are positive for collagen type 1 mutations, since little is known about the pathogenesis of the other types of the disorder. A collagen type 1 molecule consists of three polypeptide chains (two α 1 and one α 2 chain) that form a triple-helical structure.40 For the three chains to intertwine correctly they must have a glycine residue at every third position. The most typical sequence abnormality associated with osteogenesis imperfecta

Medical management of osteogenesis imperfecta

Physiotherapy, rehabilitation, and orthopaedic surgery are the mainstay of treatment for patients with osteogenesis imperfecta.61, 62 Therapeutic efforts aim to get the most out of mobility and other functional capabilities.61, 63 Physical activity programmes are encouraged—as far as is possible with the raised risk of fracture—to prevent contractures and immobility-induced bone loss.62 Orthoses are used to protect the legs during the early phases of mobilisation.64 Standing and walking can

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