Diagnosis and management of osteogenesis imperfecta

N Bishop

Children’s Bone Group, Sheffield Children’s Hospital and University of Sheffield, Sheffield, UK

Summer School 13-16 July 2004
St Anne's College, Oxford University, UK

Children with osteogenesis imperfecta (OI) suffer recurrent fractures with resulting pain, deformity and disability. The clinical phenotype ranges from very mildly affected individuals with little or no bone deformity or loss of height to lethally affected infants.

Diagnosis rests largely upon clinical history taking and examination. New molecular diagnostic approaches, in particular the use of high-throughput sequencing of genomic DNA, seem to provide the best “capture” of OI mutations, and can detect the null alleles that occur frequently in the mild form of the disease. This is of particular relevance in cases of unexplained fractures in infancy.

New forms of OI have been defined over the last five years, extending the original Sillence classification of four forms to a total of seven, each with distinct clinical and histological phenotypes. The vast majority of OI cases in OI types I-IV have mutations in the genes encoding type I collagen (COL1A1 and COL1A2). The molecular characterisation of these recently-described forms is still awaited, but the origin of their disease is not in the type I collagen genes.

The management of OI is multidisciplinary. Until the early 1990’s, surgery, occupational and physiotherapy were the mainstays of treatment. Recent approaches to medical therapy for the condition have focussed on anti-resorptive therapy using initially calcitonin and more recently bisphosphonates and anabolic therapy with growth hormone. Bone marrow transplantation has not found an established place, even in severe cases. In addition to medical therapy directed primarily at improving bone mass, symptomatic pain relief may still be required in some children and many will need surgical correction of their limb deformities.

Bisphosphonate therapy is the most widely used medical intervention and has been demonstrated to reduce fracture rate, increase bone mass, restore the architecture of previously crush-fractured vertebrae, reduce bone pain and increase mobility. There remain questions over the “best” drug, dose, route of administration an duration of therapy, as well as concerns about “over-dosing” through the inappropriate use of bisphosphonates in other groups of children, particularly those without clear evidence of underlying bone disease.

The opinions expressed in this paper are those of the speaker and do not necessarily reflect the views of the Society

Revised: 05-Nov-2004