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

Abstract

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.

New developments and therapies in pediatric endocrinology

“…Identifying the crucial pathways in the regulation of bone development and bone mass, has also led to the identification of new genetic causes of osteogenesis imperfecta, for which now more than 20 subtypes have been identified, each with its genetic cause [11].…”

Higher Sedentary Behaviors and Lower Levels of Specific Knowledge Are Risk Factors for Physical Activity-Related Injuries in Saudi Adolescents

“…This can lead to abnormal movement mechanics and decreased motor performance during maximum speed at height [44]. Bone mineralization may also not be in line with its linear growth and therefore the bone is temporarily more porous, so there is an increased risk of fractures throughout the bone and growth plate [11,45]. All of these events, acting separately or together, render the immature musculoskeletal system less able to cope with traumatic situations and repetitive biomechanical stresses [10].…”

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