Burn-induced heterotopic ossification from incidence to therapy: key signaling pathways underlying ectopic bone formation

Abstract

Burn injury is one of the potential causes of heterotopic ossification (HO), which is a rare but debilitating condition. The incidence ranges from 3.5 to 5.6 depending on body area. Burns that cover a larger percentage of the total body surface area (TBSA), require skin graft surgeries, or necessitate pulmonary intensive care are well-researched risk factors for HO. Since burns initiate such complex pathophysiological processes with a variety of molecular signal changes, it is essential to focus on HO in the specific context of burn injury to define best practices for its treatment. There are numerous key players in the pathways of burn-induced HO, including neutrophils, monocytes, transforming growth factor-β1-expressing macrophages and the adaptive immune system. The increased inflammation associated with burn injuries is also associated with pathway activation. Neurological and calcium-related contributions are also known. Endothelial-to-mesenchymal transition (EMT) and vascularization are known to play key roles in burn-induced HO, with hypoxia-inducible factor-1 (HIF-1) and vascular endothelial growth factor (VEGF) as potential initiators. Currently, non-steroidal anti-inflammatory drugs (NSAIDs) and radiotherapy are effective prophylaxes for HO. Limited joint motion, ankylosis and intolerable pain caused by burn-induced HO can be effectively tackled via surgery. Effective biomarkers for monitoring burn-induced HO occurrence and bio-prophylactic and bio-therapeutic strategies should be actively developed in the future.

Effect of Puerarin on Osteogenic Differentiation in vitro and on New Bone Formation in vivo

“… 65 The AOD value showed puerarin increased ALP and BMP2 expression levels during RME, thereby upregulating bone regeneration. Heterotopic ossification (HO) is one of the hot spots of research on post-traumatic complications, 66 , 67 and it has been reported that elevated BMP2 is positively correlated with the occurrence of HO. 68 It is noteworthy that though puerarin upregulates BMP2 level when it is used to stimulate osteogenesis in mid-palatal suture, we presume that HO is less likely to occur in the context of safe, physiological, controlled RME.…”

Heterotopic ossification after alloplastic temporomandibular joint replacement: a case cohort study

“…In addition, we found that pain scores were significantly higher in HO patients than non-HO patients both before and after operation. High pain scores may reflect local inflammation around the joint which may affect bone metabolism and lead to the occurrence of HO after surgery [37][38][39]. HO is also a major cause of postoperative pain.…”

Panniculitis Ossificans in Posterior Knee: An Unusual Presentation

“…Unlike calcification lesions, HO leads to a complete bone microenvironment within bone tissue cells, microcirculation, and neuroendocrine function. HO patients can experience pain and limited range of motion, which seriously impairs their activity of daily living [3]. Pathogenesis is not yet clear, although some studies found that it's multifactorial and the major factor identified is trauma.…”