Apyrase as a novel therapeutic inhibitor of heterotopic ossification

Olin D. Liang, Anthony M. Reginato, Damian Medici


Heterotopic ossification (HO) is a disabling disorder where endochondral bone forms in soft tissue (1). Genetic diseases, traumatic injuries, or severe burns can induce this pathological condition and can lead to severe immobility (2). While the mechanisms by which the bony lesions arise are not completely understood, intense inflammation associated with musculoskeletal injury and/or highly invasive orthopaedic surgery is thought to induce HO. The incidence of HO has been reported between 3% and 90% following total hip arthoplasty or severe fracture of the long bones (3). While the vast majority of these cases are asymptomatic, some patients will present decreased range of motion and painful swelling around the affected joints leading to severe immobility. In severe cases, ectopic bone formation may be involved in implant failure, leading to costly and painful revision surgery (4). Currently, no treatment modalities exist for HO and attempts to prevent the ectopic formation of bone have had only limited success. Early diagnosis of the formation of ectopic bone is complicated by the absence of calcium in the matrix during the first few weeks following surgery, making X-ray detection of ectopic bone very difficult. Prophylactic radiation therapy, anti-inflammatory, and bisphosphonates agents have shown some promise in preventing HO, but their effects are mild to moderate at best and complicated with adverse effects (5). Furthermore, none of these treatment modalities target key signaling pathways critical in the development of the extra skeletal bone tissue formation.

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