In the past, the primary interventions for OI consisted of deformity correction by surgical intervention, physiotherapy, orthotic support(s), and mobility-assistance devices, such as wheelchairs. As the molecular nature of this disease has become better understood, pharmacotherapy is being increasingly employed to augment bone mass and strength. Surgical intervention is kept in reserve for functional improvement.

Synthetic pyrophosphate analogues—such as bisphosphonates (particularly pamidronate)—inhibit osteoclast-mediated bone resorption. Because osteoblastic new bone formation is unopposed, cortical thickness increases, yielding stronger bone tissue. Intravenous administration of pamidronate is effective in infants, and its administration may ameliorate the natural course of the disease. In particular, pamidronate decreases the rate of fractures, increases bone mineral density, decreases bone pain, and contributes to increased height. Growth hormone may be given to act on the growth plate and stimulate osteoblast function. The patient with a quantitative collagen defect may derive somewhat greater benefit from growth hormone administration; however, the role of growth hormone has yet to be clearly delineated.