Stopping Excessive Bone Growth Following Trauma or Surgery

Researchers at Thomas Jefferson University (Jefferson, Philadelphia, PA, USA) examined the synthetic retinoid NRX195183, a potent and highly selective retinoic acid receptor alpha (RARalpha) agonist, to see if it inhibited chondrogenesis in mouse limb-micromass cultures. The researchers hoped that it would also inhibit HO, since chondrogenesis requires a decrease of nuclear RARalpha action. To do so, the researchers established a mouse HO model consisting of subcutaneous implantation of Matrigel mixed with rhBMP-2. Control mice that received daily oral doses of peanut oil or retinol (a natural nonactive retinoid precursor) developed large HO-like masses by days 9-12 that displayed abundant cartilage, endochondral bone, vessels, and marrow. In contrast, formation of HO-like masses was markedly reduced in the study companion mice that received daily oral doses of the alpha-agonist. The study was published in the September 2009 issue of the Journal of Orthopedic Research.

"We are able to largely prevent formation and progression of HO lesions,” said primary investigator Maurizio Pacifici, Ph.D, director of orthopedic research at Jefferson. "We presented our initial results at a recent U.S. Army Extremity War Injuries Symposium in Washington D.C., and they were very well-received and have elicited great hope on the part of military physicians to finally have a way to stop HO in troops wounded in war zones.”

Heterotopic ossification (HO) consists of formation of ectopic cartilage followed by endochondral bone and is triggered by major surgeries, large wounds, and other conditions. The excessive bone forms within muscles and other tissues, causing severe pain, reduced mobility, and even local paralysis if untreated. Current therapies, including low-dose irradiation, are not always effective and do not target the skeletogenic process directly. Hopefully, if clinical trials prove successful, the proposed treatment could be used as a cure for not only HO but for other HO-related diseases including Fibrodysplasia Ossificans Progressive (FOP), an inheritable and severe form of HO.

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