Heterotopic Ossification: Basic-Science Principles and Clinical Correlates

Abstract

➤ Heterotopic ossification occurs most commonly after joint arthroplasty, spinal cord injury, traumatic brain injury, blast trauma, elbow and acetabular fractures, and thermal injury.➤ The conversion of progenitor cells to osteogenic precursor cells as a result of cell-mediated interactions with the local tissue environment is affected by oxygen tension, pH, availability of micronutrients, and mechanical stimuli, and leads to heterotopic ossification.➤ Radiation and certain nonsteroidal anti-inflammatory medications are important methods of prophylaxis against heterotopic ossification.➤ Well-planned surgical excision can improve patient outcomes regardless of the joint involved or the initial cause of injury.➤ Future therapeutic strategies are focused on targeted inhibition of local factors and signaling pathways that catalyze ectopic bone formation.

Copyright © 2015 by The Journal of Bone and Joint Surgery, Incorporated.

Figures

Fig. 1

Histopathologic evidence of heterotopic ossification (hematoxylin and eosin). Fig. 1-A Early heterotopic ossification. The appearance of early heterotopic ossification may resemble reactive fibroblastic lesions. The photomicrograph shows the cellular proliferation of fibroblasts arranged in gently undulating C and S-shapes (×200). Fig. 1-B Densely mineralized osteoid interspersed with a loose and edematous fibroblastic proliferation (×40). Fig. 1-C A higher-magnification image demonstrates the tendency for maturation along the periphery of the lesion (lower left) in comparison with the more central areas (upper right) (×100). Prominent bone-lining osteoblasts are noted throughout the lesion.

Fig. 2

The common locations of heterotopic ossification are indicated according to the mechanism of injury. The numbering system from 1 (highest) to 3 (lowest) indicates decreasing prevalence of heterotopic ossification at the indicated joint based on the mechanism of injury. SCI = spinal cord injury, and TBI = traumatic brain injury.

Fig. 3

Burn injury and the resulting hypoxic environment increase HIF-1α production, which leads to angiogenesis as a result of increased levels of VEGF. Angiogenesis is an important step in the process of bone formation. MSC = mesenchymal stem cell.