Local injection of a hexametaphosphate formulation reduces heterotopic ossification in vivo.

Abstract

Heterotopic ossification (HO), the pathological formation of ectopic bone, is a debilitating condition which can cause chronic pain, limit joint movement, and prevent prosthetic limb fitting. The prevalence of this condition has risen in the military population, due to increased survivorship following blast injuries. Current prophylaxes, which aim to target the complex upstream biological pathways, are inconsistently effective ​and have a range of side-effects that make them unsuitable for combat-injured personnel. As such, many patients must undergo further surgery to remove the formed ectopic bone. In this study, a non-toxic, U.S. Food and Drug Administration (FDA) -approved calcium chelator, hexametaphosphate (HMP), is explored as a novel treatment paradigm for this condition, which targets the chemical, rather that biological, ​bone formation pathways. This approach allows not only prevention of pathological bone formation ​but also uniquely facilitates reversal, which current drugs cannot achieve. Targeted, minimally invasive delivery is achieved by loading HMP into an injectable colloidal alginate. These formulations significantly reduce ​the length of the ectopic bone formed in a rodent model of HO, with no effect on the adjacent skeletal bone. This study demonstrates the potential of localized dissolution as a new treatment ​and an alternative to surgery ​for pathological ossification and calcification conditions.