Correctly known as osteogenesis imperfecta - this is a genetic or heritable disorder characterized by poor collagen formation. The net effect is that there is less bone substance present - bone density is markedly reduced. As a result of this, frequent fractures occur with progressive deformity of the bones, decreased height (when spinal vertebra are involved), loss of mobility sometimes to the extent that the child is wheelchair bound. In addition, there is chronic bone pain associated with this disorder. In addition, there is one other outstanding characteristic and that is the sclerae (or "whites" of the eyes) are blue rather than the normal white color. There are various biochemical abnormalities but these are beyond the scope of this article.
A study was done from the genetics unit of the famous Shriner's Hospital for Children and the departments of pediatrics and surgery at McGill University and reported in The New England Journal of Medicine, Vol. 339, No. 14, pp. 947-952. It involved the use of a new medication that had been tried on few patients - named pamidronate. The time began in late 1992 and the trial was continued for five years - a considerable period of observation. Thirty children were included with an age range of three to sixteen years and all had severe or fairly severe forms of osteogenesis imperfecta. They all had severe reduction in bone density and 27 of 30 were small for their age. All but five had moderate to severe restriction in ambulation.
Before this substance was used there was no medication of benefit to a patient stricken with this disorder. Physical therapy was all that could be done.
In addition to various biochemical studies, other observations were made. Serial x-rays of various bones were taken, usually every six months (the radiologists who did the interpretation were unaware of the treatment status of the patient for greater objectivity in evaluation). In addition, subjective responses such as bone pain were duly noted. Occupational therapists experienced in the care of such children evaluated mobility and ambulation using a specific five point scale.
One of the most outstanding results was significant reduction in bone pain and this occurred in all 30 subjects. In addition, the bone density measurements showed improvement. As a result, new fractures were significantly reduced and the degree of ambulation was increased considerably. For example, when the study began, 16 of the children were confined to a bed or wheelchair and the ambulation scores of the group improved - six gained one grade, five gained two grades, and one gained three grades. (Four children progressed from being wheelchair bound to walking independently.) In the other children no change in the grade occurred during this period of observation.
The administration of pamidronate resulted in a fairly rapid increase in the density of bones and this is what accounted for the improvement. The radiologists found no new vertebral crush fractures during the period of observation and also an increase in vertebral height was observed. While fractures continued to occur it was at a much reduced rate - prior to the onset of therapy the incidence of fractures was on average 2.3 per year and this was reduced to 0.6 per year during treatment. In fact, nine children had no new fractures during treatment. Measuring bone mineral density is an excellent way to evaluate patients to see if improvement occurs and there was a positive correlation with clinical improvement.
While this is only one study, and an observational one at that (that is to say no placebo control or double-blind methodology), it is still strongly suggestive of the value of this medication. It is not a cure, however, as was mentioned in the companion editorial by Joan C. Merini, M.D. of the National Institutes of Health. She gave a thoughtful review of this entity and clearly re-emphasized the marked susceptibility of these patients to fractures, even after minimal trauma. She observed that all other treatments used were unsuccessful, such as fluoride and calcitonin. (The medication used in this study was previously found to be effective in patients with osteoporosis and Paget's disease of bone.) She reiterated some of the results found in the study and then discussed other possible future modalities such as gene therapy. She did admit that study indicates that pamidronate, although not a cure, may be the way to bring about considerable improvement. I would say that she was cautiously optimistic. At last now something can be done to improve the plight of patients with this disorder.October 1998
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