The pathophysiology of heterotopic ossification: Current treatment considerations in dentistry

SummaryHeterotopic ossification (HO) consists of the formation of ectopic cartilage followed by endochondral bone, and is triggered by major surgeries, large wounds, and other conditions. Daily functions of HO patients can be hampered by the loss of normal posture, pain, inflammation, reduced mobility, formation of pressure ulcers, deep venous thrombosis, and other complications. Research so far revealed the molecular and cellular pathways leading HO formation, and proposed several possible mechanisms behind such pathways. Nonsteroidal anti-inflammatory drug (NSAID) regimens and localized low-dose irradiation are currently available as prophylaxis of HO formation. However, they are not always effective and do not target skeletogenic processes directly. New therapeutic modalities targeting pathological process of HO formation, such as bone morphogenetic proteins (BMP) inhibitors like Noggin, BMP type 1 receptor inhibitor, and nuclear retinoic acid receptor-gamma (RARγ) agonists are currently under investigation. In this review, we will summarize our current understanding of the pathology and molecular and cellular mechanisms of HO, especially endochondral heterotopic ossification, and then discuss its current and future therapies. We will also discuss the potential application of heterotopic ossification in the dental field.