Neurological heterotopic ossification: novel mechanisms, prognostic biomarkers and prophylactic therapies

Abstract

Neurological heterotopic ossification (NHO) is a debilitating condition where bone forms in soft tissue, such as muscle surrounding the hip and knee, following an injury to the brain or spinal cord. This abnormal formation of bone can result in nerve impingement, pain, contractures and impaired movement. Patients are often diagnosed with NHO after the bone tissue has completely mineralised, leaving invasive surgical resection the only remaining treatment option. Surgical resection of NHO creates potential for added complications, particularly in patients with concomitant injury to the central nervous system (CNS). Although recent work has begun to shed light on the physiological mechanisms involved in NHO, there remains a significant knowledge gap related to the prognostic biomarkers and prophylactic treatments which are necessary to prevent NHO and optimise patient outcomes. This article reviews the current understanding pertaining to NHO epidemiology, pathobiology, biomarkers and treatment options. In particular, we focus on how concomitant CNS injury may drive ectopic bone formation and discuss considerations for treating polytrauma patients with NHO. We conclude that understanding of the pathogenesis of NHO is rapidly advancing, and as such, there is the strong potential for future research to unearth methods capable of identifying patients likely to develop NHO, and targeted treatments to prevent its manifestation.

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Funding

U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NINDS)(NINDS RFA-NS-16-012)