A three-year study tracked dozens of patients suffering from an extremely rare disorder that gradually transforms muscles, tendons, and ligaments into bone. This lifelong condition is known as Fibrodysplasia Ossificans Progressiva (FOP). While estimates of its prevalence vary, confirmed cases occur in approximately one out of every one to two million births. Only about 800 patients worldwide have been diagnosed with Fibrodysplasia Ossificans Progressiva, and in 2006, researchers found that 97% of patients shared the same genetic variant of the disease. This mutation occurs in the gene that encodes for a bone growth regulation receptor, which seems to cause stem cells to produce bone tissues in areas where they typically shouldn’t be found.
Due to the rarity of FOP, researchers hope that the findings of the current study will enable doctors to better address the medical needs of underserved patients. It is noted that the progressive calcification of soft tissues due to FOP is not steady and comes in waves. Attacks usually begin in childhood, often starting in the neck and shoulders. The hard tissue spreads over the joints, gradually limiting movement, fixing body parts in place, and reducing the lifespan of those affected. Not everyone with Fibrodysplasia Ossificans Progressiva shows the same rate of calcification, but once bone is formed in any part of the body, it is permanent, making most affected individuals require a wheelchair by their twenties.
Unfortunately, no treatments are available for Fibrodysplasia Ossificans Progressiva to date, although pain and swelling that patients experience can be somewhat alleviated with medication. Throughout a patient’s life, the disease and physical traumas can cause swellings in muscle areas, and inflammatory responses can last from days to months, often leading to bone formation thereafter. If these events can be minimized, there is a chance that the progression of the disorder may be halted.
The recent long-term study is among the first to investigate the development of Fibrodysplasia Ossificans Progressiva in 114 patients, as previous studies had relied on patient reports. Only 33 individuals completed the three-year study, which included regular check-ups (most of them moved on to participate in clinical trials for possible drug interventions). Ultimately, researchers found that 82 patients (over 70% of the original group) reported a total of 229 inflammatory episodes, typically in the upper back but also in the hip, shoulder, and lower spine. After twelve weeks from an episode, researchers often found that new bone had accumulated at the site of inflammation or pain.
Although the progression of Fibrodysplasia Ossificans Progressiva seems to slow down with age, 70% of individuals aged 25 to 65 displayed new bone volume in annual study examinations. The most commonly reported symptoms during these visits were severe pain, swelling of soft tissues, and extremely restricted movement. The researchers concluded that "the findings obtained from individuals receiving standard care for up to 3 years in this study illustrate the debilitating effect and progressive nature of Fibrodysplasia Ossificans Progressiva both transversely and longitudinally, with the greatest advancement occurring during childhood and early adulthood."
The results reveal that the most commonly used continuous medications by patients are non-steroidal anti-inflammatory drugs. However, during the study, nearly 80% of participants started a new medication, indicating they were desperately seeking something that could help them feel better. Fibrodysplasia Ossificans Progressiva does not only affect the musculoskeletal system; patients involved in the study commonly faced respiratory issues such as reduced chest expansion (which can be life-threatening) and hearing loss. Each participant exhibited internal deformities in the growth of their big toes, supporting the idea that this might be one of the first signs of the disorder, believed to be present at birth.
If doctors can recognize these clear early signs of Fibrodysplasia Ossificans Progressiva, genetic testing could be conducted early to expedite diagnosis and potentially delay disease progression. If diagnosis takes too long without effective management of the condition and its symptoms, there is a greater risk of injuries or muscle strain accelerating the stiffness of soft tissues. High doses of corticosteroids taken for four days during an episode have proven highly effective in reducing inflammation associated with excessive bone growth. The new study, along with ongoing clinical trials, may help improve the lives of those dealing with this rare condition in the coming years. The study's findings have been published in the journal *Genetics in Medicine*.
