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Osteogenesis Imperfecta-Update
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Dr. Francis H. Glorieux, OC, MD, PhD
Professor of Surgery, Pediatrics, and Human Genetics,
McGill University

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Osteogenesis Imperfecta (OI) is a heritable disorder characterized by bone fragility caused by alterations in bone quantity and quality. The observed bone abnormalities such as high turnover rate and bone loss provide justification for the use of bisphosphonates in order to reduce osteoclast mediated bone resorption.
Currently, the most common bisphosphonate therapy for OI is cyclical intravenous pamidronate (PAM) administration. PAM at the dosage of 9mg/kg/yr reduces bone pain, decreases the fracture incidence, increases the level of ambulation, and increases both bone size and density. Effects on bone include increase in size of vertebral bodies and thickening of the cortical envelope. If the patient is younger, the therapeutic effects might be more striking. Although there are some adverse events at first exposure to the drug (e.g. fever), no negative effects on growth, modeling or fracture repair have been observed. Extremely rare adverse events of bisphosphonate in the acute phase include respiratory distress due to bronchospasm, which is not recurrent. There is so far no evidence of osteonecrosis of the jaw in childhood OI treated with appropriate doses of bisphosphonates.
Current reports indicate that oral alendronate has a lesser effect than the intravenous drugs. Randomized placebo-controlled study of risedronate in mild pediatric OI demonstrated no evidence of benefit. These drugs are unconvincing for treating OI at present.
Compared with PAM, zoledronic acid (ZOL) requires a smaller amount and has a longer effect. Randomized study in moderate to severe OI patients revealed that ZOL induced significant increase in bone density and decrease in fracture incidence. These effects were comparable to those of PAM. Because of its ease and safety, ZOL is likely to become the first choice among intravenous bisphosphonates for treating OI.
The benefit of using bisphosphonate for mild OI has not been established. For moderate to severe OI, the therapy is most effective when started as early as possible. How long to treat, and when to stop bisphosphonates remains an open question. In growing individuals, treatment should probably be maintained until the epiphyses are fused, at half the initial dose of intravenous PAM. However, long-term bisphosphonate therapy will suppress bone turnover to levels lower than those in healthy children and the consequences of chronically low bone turnover in children with OI are unknown at the present time.
In addition to medical treatment, corrective surgery using intramedullary rodding of the long bones and paravertebral instrumentation as well as physiotherapy programs are also important and efficacious.

Besides bisphosphonate therapy, further strategies for treating OI aiming at inhibition of bone resorption include Rankl inhibitors and CatK inhibitors. Those aiming at acceleration of bone formation include serotonin inhibitors and sclerostin inhibitors.

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