Nearly 30% of children suffer a fracture during till the end of growth. Most of these fractures are accidental fractures and many are located at the forearm. Non accidental fractures can by caused due to an appropriate force (e.g. child abuse) or can be classified as pathological fractures which are often caused by benign tumours like bone cysts, non-ossifying fibroma or fibrous dysplasia. Most reasons for fractures can be detected by carefully recording the medical history of the patient and the family. In cases without a traumatic history or non-accidental injury additional laboratory tests to exclude metabolic reasons of decreased bone stability are necessary. Radiographs which have been taken of the fractured bone can also give some first impressions about bone structure, modelling of the bone and of the mineralization. After excluding systematic and metabolic reasons for a reduced bone mass, many different types of skeletal dysplasia can cause a reduced bone stability. The most frequent hereditary disease causing an increased fracture rate in children and adolescents is Osteogenesis imperfecta (OI) with an incidence of 1:20,000 births. Osteogenesis imperfecta is primarily a clinical diagnosis but during the last years the knowledge about the molecular reasons for impaired bone stability has increased tremendously. Most patients are affected by dominant mutations involving collagen production (COL1A1/A2) causing a reduced amount of bone matrix, which can additionally show an impaired bone mineralization. Besides these typically types of OI many different genes (most of them recessive ones) have been discovered to cause diseases belonging to the spectrum of hereditary bone fragility syndromes. Some of these rare types can be differentiated by characteristic clinical findings, like the calcified membrane interossea at the forearm in OI type 5 or the combination of fractures and contractures in Bruck-Syndrom. Other types are characterized by increased bone mineral density (caused by mutations in BMP) or an increased amount of osteoid in bone biopsies like OI type 6. Not all different diseases can be diagnosed based on clinical findings and therefore genetic testing including bone panels or Exome Sequencing is frequently necessary to find the correct diagnosis which is important for treatment of patients and counselling of families.
10 - 12 Sep 2016
European Society for Paediatric Endocrinology