Hereditary Metabolic Bone Diseases: A Review of Pathogenesis, Diagnosis and Management

Hereditary metabolic bone diseases are characterized by genetic abnormalities in skeletal homeostasis and encompass one of the most diverse groups among rare diseases. In this review, we examine 25 selected hereditary metabolic bone diseases and recognized genetic variations of 78 genes that represent each of the three groups, including sclerosing bone disorders, disorders of defective bone mineralization and disorder of bone matrix and cartilage formation. We also review pathophysiology, manifestation and treatment for each disease. Advances in molecular genetics and basic sciences has led to accurate genetic diagnosis and novel effective therapeutic strategies for some diseases. For other diseases, the genetic basis and pathophysiology remain unclear. Further researches are therefore crucial to innovate ways to overcome diagnostic challenges and develop effective treatment options for these orphan diseases.

Automated summary

Hereditary metabolic bone diseases encompass a diverse group of rare diseases with genetic abnormalities in skeletal homeostasis. This review examines 25 selected diseases and genetic variations of 78 genes, covering sclerosing bone disorders, disorders of defective bone mineralization, and disorder of bone matrix and cartilage formation. Advancements in molecular genetics have enabled accurate genetic diagnosis and novel therapeutic strategies for some diseases, but further research is needed for diseases with unclear genetic basis and pathophysiology.