Osteogenesis Imperfecta
— What you need to know in 2006

We are most fortunate in Australia that Professor David Danks and Lucille Stace (Hutchinson) decided in 1971 to undertake a study of inherited bone disorders in Victoria. We are also indebted to Little People of Australia (LPAA) who funded the study <http://www.sspa.org.au/>. It became apparent that approximately half of all the people in the community with genetic bone disorder had some form of the brittle bone disorder, Osteogenesis Imperfecta (OI). In 1975, very little was known, except there appeared to be a wide range of severity, from very "mildly" affected people who might have the occasional fracture through to extremely severely affected babies who had literally hundreds of fractures before birth. At the time it was believed there was one disorder. The 3-year period, between 1975-1977, went on to show there were at least four disorders accounting for the variability in OI. We named (numbered) the disorders in order of their delineation. Type I - Dominantly inherited with distinctly blue sclerae +/- conductive hearing loss II - Perinatally lethal OI with ribs III - Progressively deforming OI with normal sclerae IV - Dominantly inherited OI with normal sclerae Over the last three decades of study it has become clear there are many more types of OI and considerable variability within families and within each type of OI. The Colour of the Sclerae The presence of distinctly blue-grey sclerae for life, still strongly predicts certain features of the disorder known as OI type I. It is still unknown what substance contributes to the blue colour but it is not due to thinning of the sclerae (the 'whites' of the eyes). People with OI type I, have the highest frequency of conductive hearing loss/mixed hearing loss and easy bruising. They are very responsive to bisphosphonate therapies. People with OI type IV have bluish or normal sclerae in childhood. Opalescent Dentine Some people with OI have obviously brittle teeth. When these erupt they appear light brown or grey. Fluoride intake modifies the colour. Opalescent dentine, which is also seen in the condition Dentinogenesis Imperfecta, is associated with an increased risk of fractures before birth, basilar impression and scoliosis. Inheritance Patterns In European countries, the predominant pattern of inheritance is autosomal dominant but in Southern and Northern Africa/Middle East, autosomal recessive forms of OI predominate. How do we make a diagnosis of OI Fracture history Family history (when there is none, we call this sporadic) Bone x-ray findings Measurement of bone 'metabolism' such as deoxypyridinoline/creatinine excretion in urine Measurement of bone density Bone biopsy (selected children) Collagen biochemistry and DNA molecular analysis Bone Biopsy The newer types of OI (types V, VI and VII) were all distinguished on the basis of their bone when subjected to a special type of study known as histomorphometry. This resource is not available at present for all children in Australia. Collagen biochemistry and DNA molecular diagnosis This is a valuable study and currently not available in Australia. It requires skilled interpretation in a clinical setting. The discovery of the genetic alteration in one of the two type I collagen genes is valuable and: correlates with OI type for OI types I-IV assists with prognosis for stature and OI complications permits genetic counselling and prenatal diagnosis in subsequent pregnancies. However, is it useful specifically for OI types I-IV and "normal" recessive OI type II and types V-VII and "ocular" types of OI. The 2005 International Nomenclature of OI This includes types of OI in addition to OI types I - IV. Type Description Inherit V Normal sclerae, calcification in forearm ligaments +/- hyperplastic callus AD VI Normal sclerae, bone biopsy shows fish scale lamellation ?AD VII Normal sclerae, short arms and thighs AR Cole-Carpenter type SP OI with joint contractures - Bruck type 1 AR OI with joint contractures - Bruck type 2 AR Osteoporosis with Pseudoglioma-ocular type 1 AR Spondylo-ocular Dysplasia-ocular type 2 AR Autosomal Recessive OI "type III" We are still ignorant about the causes in most autosomal recessive forms of OI. These disorders seem to be characteristic of different regions and population groups, eg. Southern Africa, Libya, Old Order Amish, Lebanon, Irish Gypsies, Italy, Dakota first nations. OI type VIII was distinguished because children had short humeri and femurs. It has found to result from a deficiency in 3 prolyl hydroxylation. An Australian family helped us discover he causative mechanism in the second type of Bruck syndrome. Some factors which modify the severity and complications in OI. These include: Lack of basic orthopaedic care Lack of pain relief for fractures Excessive immobilisation Basilar impression A family history of scoliosis A second bone or joint disorder such as Arthrogryposis Lack of access to bone and mineral management services to treat the osteoporosis Lack of rehabilitation services to facilitate living in the home and access to school and the work place What can we do? Sadly many children (and adults) in Australian and New Zealand, not to mention our neighbours receive inadequate care. We need to find some way to work with: Osteoporosis Australia, and the Decade of Bone and Joint Health to increase awareness and participation of all families in Australia with brittle bone disorders. There are some dogmas that need to be broken down - OI is a rare disease, Children don't suffer from osteoporosis. There is much yet to be done in regards to OI.   by Prof David Sillence, Discipline of Genetic Medicine, University of Sydney, the Children's Hospital at Westmead NSW Australia - talk given at the 9th National conference on Osteogenesis Imperfecta, 2006. http://www.medfac.usyd.edu.au/people/academics/profiles/davids.php

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