Osteogenesis imperfecta (OI) is a hereditary disease characterized by skeletal findings like increased fracture rate, deformed long bones and vertebral compression fractures. Non-skeletal findings include hypermobility of joint, hearing and dental impairments and weakness of collagen involving structures like vessels and valves. Therapy is based on an interdisciplinary approach including orthopaedic surgery to correct deformities, physiotherapy to increase musclefunction and pharmacological treatment. During the last two decades antiresorptive therapy with bisphosphonates are more and more frequently used to treat patients with moderate or severe types of OI. Bisphosphonates bind permanently to the bone and stay there for many years or decades. Bisphophonates are frequently used to treat osteoporosis in elderly but they are only approved for the treatment of OI in very few countries. When treating children special caution has to be given to long term side effects. In the treatment of osteoporosis concerns about impairments of bone remodelling after longtime bisphosphonate treatment have been raised regarding occurrence of pathological fractures (femur) and osteonecrosis of the jaw. Recently the RANKL-Antibody Denosumab has become available for the treatment of postmenopausal osteoporosis and is also approved in a few other oncological indications with increased bone resorption. A benefit of the antibody might be the direct interaction with the osteoclasts and a complete resorption after a few months. Denosumab has been used in very rare indications in children and has proven to be highly effective in reducing osteoclastic activity. In a growing skeleton it seems that the risk of a severe hypocalcemia after application is more prominent than in adults and calcium has to be monitored closely and substituted with high doses of oral calcium for a few weeks. A pilot trial of 1 year involving 10 severely affected OI children showed a higher increase of areal bone mineral density (aBMD) than it was achieved during the previous treatment with bisphosphonates. It has to be kept in mind that it is not clear which would be the best aBMD for OI patients. Special concerns have to be given to a rebound hyper-calcemia and -calciuria at the end of the treatment period which might cause nephrocalcinosis and calcification of vessels and has to be studied in detail in the future.
10 - 12 Sep 2016
European Society for Paediatric Endocrinology