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Contemporary perspectives on heterotopic ossification
Charles D. Hwang, … , Aaron W. James, Benjamin Levi
Charles D. Hwang, … , Aaron W. James, Benjamin Levi
Published July 22, 2022
Citation Information: JCI Insight. 2022;7(14):e158996. https://doi.org/10.1172/jci.insight.158996.
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Review

Contemporary perspectives on heterotopic ossification

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Abstract

Heterotopic ossification (HO) is the formation of ectopic bone that is primarily genetically driven (fibrodysplasia ossificans progressiva [FOP]) or acquired in the setting of trauma (tHO). HO has undergone intense investigation, especially over the last 50 years, as awareness has increased around improving clinical technologies and incidence, such as with ongoing wartime conflicts. Current treatments for tHO and FOP remain prophylactic and include NSAIDs and glucocorticoids, respectively, whereas other proposed therapeutic modalities exhibit prohibitive risk profiles. Contemporary studies have elucidated mechanisms behind tHO and FOP and have described new distinct niches independent of inflammation that regulate ectopic bone formation. These investigations have propagated a paradigm shift in the approach to treatment and management of a historically difficult surgical problem, with ongoing clinical trials and promising new targets.

Authors

Charles D. Hwang, Chase A. Pagani, Johanna H. Nunez, Masnsen Cherief, Qizhi Qin, Mario Gomez-Salazar, Balram Kadaikal, Heeseog Kang, Ashish R. Chowdary, Nicole Patel, Aaron W. James, Benjamin Levi

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Figure 1

HO induces reactivation of developmental programs found in bone.

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HO induces reactivation of developmental programs found in bone.
Bone de...
Bone development in traumatic and genetic forms of HO is initiated by a range of inflammatory responses and recapitulation of developmental bone biology, via both predictable patterns of direct mesenchymal progenitor cell (MPC) differentiation into bone-forming osteoblasts (intramembranous ossification, top progress bar) and the deposition of cartilagenous scaffold via chondroblasts and subsequent infiltration and differentiation of osteoblasts (endochondral ossification, bottom progress bar). These yield robust formation of bony lesions typified in the appendicular skeleton in traumatic HO versus the axial skeleton in genetic forms, i.e., fibrodysplasia ossificans progressiva (FOP) (bottom).

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