UNASSIGNED: Diagnosis of sclerosing and hyperostotic bone disorders (SHS) is challenging. The correct and early identification of SHS can have therapeutic, prognostic and, in case of genetic SHS with regard to the risk of inheritance, advisory consequences.
UNASSIGNED: For diagnosis, radiographic examinations and supplementary computed tomography (CT) and magnetic resonance imaging (MRI) are used. These are of indicative nature. Definitive diagnosis is usually made by genetic differentiation.
UNASSIGNED: In combination with the age of the affected person and the location of the osseous changes the characteristic image criteria are important. These are summarized in groups in this overview.
UNASSIGNED: Projection radiography in two planes is the imaging modality of choice. CT and MR can detect additional differential diagnostic criteria and should be indicated when needed.
UNASSIGNED: KLINISCHES/METHODISCHES PROBLEM: Die bildgebende Diagnostik von sklerosierenden hyperostotischen Skelettveränderungen (SHS) ist eine Herausforderung. Die korrekte und frühzeitige Identifizierung von SHS kann therapeutische, prognostische und, vorrangig bei genetisch bedingten SHS hinsichtlich des Vererbungsrisikos, beratende Konsequenzen haben.
UNASSIGNED: Zur Abklärung werden projektionsradiographische Untersuchungen sowie ergänzend Computertomographie (CT) und Magnetresonanztomographie (MRT) eingesetzt. Diese haben hinweisenden Charakter. Die definitive Diagnosestellung erfolgt regelhaft durch genetische Differenzierungen.
UNASSIGNED: Entscheidend sind die charakteristischen Bildkriterien. Diese sind in der vorliegenden Übersicht in Gruppen zusammengefasst und dienen in Kombination mit dem Alter der Betroffenen und der Lokalisation der ossären Veränderungen als differenzialdiagnostische Entscheidungshilfe. EMPFEHLUNG FüR DIE PRAXIS: Grundsätzlich ist die Projektionsradiographie in 2 Ebenen das bildgebende Verfahren der Wahl. CT und MRT können differenzialdiagnostische Zusatzkriterien erfassen und sollten fakultativ indiziert werden.

Bone mineral density (BMD) is a quantitative traits used as a surrogate phenotype for the diagnosis of osteoporosis, a common metabolic disorder characterized by increased fracture risk as a result of a decreased bone mass and deterioration of the microarchitecture of the bone. Normal variation in BMD is determined by both environmental and genetic factors. According to heritability studies, 50-85% of the variance in BMD is controlled by genetic factors which are mostly polygenic. In contrast to the complex etiology of osteoporosis, there are disorders with deviating BMD values caused by one mutation with a large impact. These mutations can result in monogenic bone disorders with either an extreme high (sclerosteosis, Van Buchem disease, osteopetrosis, high bone mass phenotype) or low BMD (osteogenesis imperfecta, juvenile osteoporosis, primary osteoporosis). Identification of the disease causing genes, increased the knowledge on the regulation of BMD and highlighted important signaling pathways and novel therapeutic targets such as sclerostin, RANKL and cathepsin K. Genetic variation in genes involved in these pathways are often also involved in the regulation of normal variation in BMD and osteoporosis susceptibility. In the last decades, identification of genetic factors regulating BMD has proven to be a challenge. Several approaches have been tested such as linkage studies and candidate and genome wide association studies. Although, throughout the years, technological developments made it possible to study increasing numbers of genetic variants in populations with increasing sample sizes at the same time, only a small fraction of the genetic impact can yet be explained. In order to elucidate the missing heritability, the focus shifted to studying the role of rare variants, copy number variations and epigenetic influences. This review summarizes the genetic cause of different monogenic bone disorders with deviating BMD and the knowledge on genetic factors explaining normal variation in BMD and osteoporosis risk.