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.
Highlights
Heterotopic ossification (HO) is the pathological formation of bone in muscles and surrounding joints
Role of neuropeptides Neuronal injury can trigger neurogenic inflammation, which in the context of moderate-severe traumatic brain injury (TBI) or spinal cord injury (SCI) has been shown to muscle injury, mice were injected intravenously with clodronateloaded liposomes to deplete resident tissue macrophages.[12] exacerbate secondary injury pathologies such as neuronal cell death,[82] BBB83 and BSB,[82] oedema,[83] ischaemia[83] and hypoxia.[84]. Ablation of these resident tissue macrophages was found to Neurogenic inflammation has been associated with the release of reduce Neurological heterotopic ossification (NHO) volume by ~90%, and completely prevent NHO development in 3/11 mice.[12]. These findings indicate that macrophages likely play a prominent role in SCI-induced NHO
While in the mouse model, antagonising substance P (SP) receptor neurokinin-1 receptor (NK-1R) with RP67580 reduced NHO volume by ~30%.12. These findings indicate that SP may represent both a prognostic biomarker of NHO and a treatment target, whereby an intervention that downregulates SP is initiated following elevated plasma levels of SP
Summary
GCS 3: 9 Coma duration of 76 patients: 10.03 (1–61 days) Mechanical ventilation: 8.95 (0–52 days) Diffuse axonal injury: 7 patients. The precise mechanisms are unclear, it has been theorised that central regulation of bone formation occurs via activation of efferent pathways relayed via the brainstem.[111,112] As patient is stable enough to undergo surgery and the lesion is sufficiently mineralised to enable resection.[8,119,120,121] These changes were based on findings that earlier resection of NHO-lesions did not increase the risk of recurrence.[8,119,120,121] Further, recent evidence suggests that early excision may reduce the risk of such, damage or alterations in excitability of these neural operative complications (e.g. peri-operative fracture), enhance pathways following TBI or SCI may be a contributor to NHO bone and articular cartilage health, and reduce negative cerebral formation Supporting this hypothesis, ventromedial hypothalamic neurons have been identified as playing a key role in bone changes (e.g. atrophy of motor areas) that further inhibit ROM (see Table 2).[11,118,122] formation, with chemical lesioning of these neurons resulting in a high bone mass phenotype in mice.[113] This was thought to occur via ablation of leptin receptors which are densely populated in this region, inhibiting the osteogenic effect of leptin.[113] Resection has been associated with a number of complications. IV etidronate disodium (300 mg for 3 h, 3 doses for 3 days/5 days) followed by oral
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