Heterotopic Bone Formation About the Hip Undergoes Endochondral Ossification: A Rabbit Model

Abstract

Background Heterotopic ossification (HO) occurs most commonly after trauma and surgery about the hip and may compromise subsequent function. Currently available animal models describing the cellular progression of HO are based on exogenous osteogenic induction agents and may not reflect the processes following trauma.Questions/purposes We therefore sought to characterize the histologic progression of heterotopic bone formation in an animal model that recapitulates the human condition without the addition of exogenous osteogenic material. Methods We used a rabbit model that included intramedullary instrumentation of the upper femur and ischemic crush injury of the gluteal muscle. Bilateral surgical induction procedures were performed on 30 animals with the intention of inciting the process of HO; no supplemental osteogenic stimulants were used. Three animals were sacrificed at each of 10 predetermined times between 1 day and 26 weeks postoperatively and the progression of tissue maturation was graded histologically using a five-item scale. Results Heterotopic bone reliably formed de novo and consistently followed a pathway of endochondral ossification. Chondroid elements were found in juxtaposition with immature woven bone in all sections that contained mature osseous elements. Conclusions These results establish that HO occurs in an animal model mimicking the human condition following surgical trauma about the hip; it is predictable in its histologic progression and follows a pathway of endochondral bone formation. Clinical Relevance By showing a consistent pathway of endochondral ossification leading to ectopic bone formation, this study provides a basis for understanding the mechanisms by which HO might be mitigated by interventions.

Diminished Chondrogenesis and Enhanced Osteoclastogenesis in Leptin-Deficient Diabetic Mice (ob/ob) Impair Pathologic, Trauma-Induced Heterotopic Ossification

“…Similar to normal fracture healing, HO is believed to develop through an endochondral intermediary [4,5]. Metabolic derangements, including diabetes, can result in decreased bone mineral density and impaired fracture site healing in normal bone [6][7][8].…”

Post‐Traumatic Heterotopic Ossification: An Old Problem in Need of New Solutions

“…It has been shown that there is upregulation in key osteogenic and chondrogenic gene transcripts (BMP2, BMP3, ALPL, COLL2A1, COLL10A1, COLL11A1, COMP, CSF2, CSF3, MMP8, MMP9, SMAD1, and VEGFA) in the soft tissues of high‐energy combat wounds . The upregulation of these gene transcripts suggests an endochondral (as opposed to an intramembranous) model of development of acquired HO, something that has been confirmed separately in an animal model …”

Early Detection of Heterotopic Ossification for Effective Prevention and Treatment

“…Among the risk and predisposing factors summarized from clinical data, spreading bone marrow to the surgical field during reaming femoral canal was speculated [13] . This theory is supported by an animal study, in which HO was successfully induced in rabbits by surgical reaming of femoral medullary canal and intentionally leaving bone debris and marrow materials in the wound [14] . Bone marrow is well-known for containing mesenchymal stem cells (MSCs) and other osteogenic elements [15] .…”