![]() In practice, the designation of HO is applied to bone formation at any extra‐osseous site, including skeletal muscle, fascia, tendon, ligament, subcutis, skin, vascular wall, or virtually any site of connective tissue. These downstream signaling events inappropriately activate an osteogenic or osteochondrogenic program. HO is most commonly incited upon tissue injury, followed by an influx of inflammatory cells and subsequent downstream signaling sequelae among predominantly resident cells of mesenchymal origin. Some HO lesions may be small and clinically irrelevant, while others may exact a high morbidity. Nongenetic forms of HO are most common, but rare genetic forms of HO also exist. The word “heterotopic” is derived from the greek roots “hetero” and “topos,” meaning “other place.” HO can be conceptualized as aberrant tissue repair and is increasingly recognized as a common complication of trauma, surgery, and other local or systemic insults. Heterotopic ossification (HO) is a diverse pathologic process, defined as the formation of extraskeletal bone in muscle and soft tissues. on behalf of American Society for Bone and Mineral Research. JBMR Plus published by Wiley Periodicals, Inc. Next, current concepts regarding the mechanistic bases for HO are discussed, including the putative cell types responsible for HO formation, the inflammatory milieu and other prerequisite “niche” factors for HO initiation and propagation, and currently available animal models for the study of HO of this common and potentially devastating condition. ![]() First, the clinical features, radiographic appearance, histopathologic diagnosis, and current methods of treatment are discussed. This comprehensive review seeks to synthesize the clinical, pathoetiologic, and basic biologic features of HO, including nongenetic and genetic forms. HO can be conceptualized as a tissue repair process gone awry and is a common complication of trauma and surgery. ![]()
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