Bone Involvement in the Ehlers-Danlos Syndromes

The Ehlers-Danlos syndromes (EDS) encompass a heterogeneous group of heritable conditions that share several characteristics such as soft and hyperextensible skin, abnormal wound healing, easy bruising, and (generalized) joint hypermobility. The currently used 2017 International EDS classification recognizes 13 EDS types, caused by genetic defects in 20 different genes. Defects in different fibrillar collagens, which are distributed throughout the connective tissues of the skin, ligaments, tendons, blood vessels, and bone, lie at the molecular basis of many EDS types. Interestingly, fragility of the bone is not traditionally considered a hallmark of EDS, despite the importance of many of the causative molecules in bone development and/or homeostasis. Only a few studies have directly addressed fracture rate, bone quality, and/or density in EDS patients. Reduced bone mass density, abnormal bone structure, and/or a tendency to low-impact fractures has been reported in several EDS patients across different types, but these studies are usually confined to case studies or small case series and/or do not provide detailed information on the specific EDS type. This chapter provides a brief overview of the structure and biosynthesis of fibrillar collagens and focuses on the clinical and molecular characteristics of different types of genetically defined types of EDS, with a special emphasis on bone phenotypes reported for these conditions.