The Use of Bone Biomarkers, Imaging Tools, and Genetic Tests in the Diagnosis of Rare Bone Disorders.

Rare bone diseases are clinically and genetically heterogenous. Despite those differences, the underlying pathophysiology is not infrequently different. Several of these diseases are characterized by abnormal bone metabolism and turnover with subsequent abnormalities in markers of bone turnover, rendering them useful adjuncts in the diagnostic process. As most rare bone diseases are inherited, genetic testing for implicated pathogenic variants, where known, is another relevant tool that can aid in diagnosis. While some skeletal disorders can be localized or monostotic, others can involve multiple skeletal sites and warrant imaging tools to localize them and determine the severity of disease and/or presence of complications as well as to assess bone quality and the potential risk of fractures. Rare bone disorders pose a great challenge in their diagnosis, ultimately resulting in delayed diagnosis, higher risk of complications and a poor quality of life in affected individuals. In this review we discuss the biochemical and radiological tools that can be utilized to diagnose selected orphan bone disorders, the clinical utility and limitations of these diagnostic tools, and areas where future research is warranted.