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Background: Multiple hereditary exostoses, also termed as multiple osteochondromas, is a heritable disorder of connective tissue with primarily orthopaedic clinical manifestations. Understanding of its biological underpinnings has been advanced on a variety of fronts in recent years.

Methods: The multifaceted literature regarding osteochondromagenesis and the major clinical challenges in patients with multiple osteochondromas were reviewed.

Results: Consideration of recent advances in molecular biology, biochemistry, and animal modeling of osteochondroma pathogenesis yields a unified model.

Conclusions: Mechanistic details and therapeutic targets have yet to be elucidated, but the general biology of osteochondroma formation is increasingly clear, as well as its implications in the orthopaedic clinical setting.

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