The pathogenesis of heterotopic ossification after traumatic brain injury. A review of current literature


key, words

Published online: Feb 13 2021

Joris Anthonissen, Clara Theressa Steffen, Alexander Hofmann, Jan Victor

From Department of Orthopedics and Trauma Surgery, Ghent University Hospital, Ghent, Belgium


Neurogenic heterotopic ossification (NHO), mostly defined as a benign process of formation of bone outside the skeletal system, after traumatic brain injury (TBI) is a musculoskeletal disorder that causes pain and reduces the range of motion, often leading to marked impairment of quality of life. The pathogenic factors that link the brain and bone and cause the formation of heterotopic bone are largely unknown. This article will try to summarize the current literature on the pathogenesis of NHO and accelerated fracture healing after TBI.

The heterotopic formation of bone after TBI seems to be inducted by a complex interplay between local and systemic factors. For all different forms of HO, the same three conditions are required for the formation of ectopic bone : The presence of osteoprogenitor cells, a permissive environment, and a stimulating factor. The osteoprogenitor cells are thought to be of mesenchymal origin, however recent research suggests a possible neural origin. The permissive environment is created mainly by reactions to hypoxia and both local and sensory nerve inflammation. Many possible inducing factors have been described ; the endogenic route is thought to be the most dominant in the stimulation of HO formation after TBI.

The pathogenesis of NHO remains largely unknown, recent research, however, has discovered interesting topics for further research and new possible targets in the prevention of NHO.