severe types of OI, using heavy casts, such as hip spica casts, can cause fractures at the bones at the boundaries of the cast, as well as generalized osteopenia. The lightweight cast or splint is then replaced with a removable orthosis after a few weeks and once evidence of union is seen on X-ray. In order to prevent a nonunion or malunion, all fractures should be immobilized, even if the fracture seems trivial (microfracture), as people with OI are at greater risk of nonunion. Bone infections secondary to fractures are treated as and when they occur with the appropriate antibiotics and antiseptics, as in the general population. Medications Bisphosphonates In 1998, an initial observational trial demonstrated the effectiveness of intravenous pamidronate, a bisphosphonate which had previously been used in adults to treat osteoporosis. In severe OI, this trial showed that pamidronate reduced bone pain, prevented new vertebral fractures, reshaped previously fractured vertebral bodies, and reduced the number of long-bone fractures. Although oral bisphosphonates are more convenient and cheaper, they are not absorbed as well, and intravenous bisphosphonates are generally more effective, although this is under study. Some studies have found oral and intravenous bisphosphonates, such as oral alendronate and intravenous pamidronate, equivalent. In a 2013 double-blind trial of children with mild OI, oral risedronate increased bone mineral densities, and reduced nonvertebral fractures. However, it did not decrease new vertebral fractures. A Cochrane review in 2016 concluded that though bisphosphonates seem to improve bone mineral density, it is uncertain whether this leads either to a reduction in bone fractures or improvement in the quality of life of individuals with osteogenesis imperfecta. Even in trials with as many as 125 children, no causal link has been found between bisphosphonates and decreased fracture rates; placebo controlled trials were also unable to prove that they brought about increased strength, motor control or lower pain levels. Bisphosphonates are not as effective at increasing the bone mineral density of adults. Nutritional supplements OI is a genetic disorder and is not caused by insufficient intake of any vitamin or mineral; supplementation cannot cure OI. With that said, people with OI tend to be severely deficient in vitamin D at much higher rates than the general population, and the cause of this is not well understood. The severity of the deficiency and the likelihood of its occurrence is thought to be related to severity of OI. Vitamin D