A three-year study followed dozens of patients with an ultra-rare disease that gradually turns muscles, tendons and ligaments into bone.
This lifelong irreversible condition is known as fibrodysplasia ossificans progressiva (FOP). Although estimates of its prevalence vary, confirmed cases occur in approximately one in 1 to 2 million births.
Only about 800 patients were diagnosed with FOP worldwide, and in 2006 it was discovered that 97 percent of patients harbor the same genetic variant of the disease.
This mutation occurs in a gene that codes for a receptor regulating bone development, appearing to cause stem cells to produce bone tissue in places that usually shouldn’t have any.
Given the severity and rarity of FOP, it is hoped that the results of current research will allow physicians to better meet the medical needs of underserved patients.
Progressive soft tissue calcification in FOP is not constant; it comes in waves. Episodes usually begin in childhood and tend to begin in the neck and shoulders, causing bands, sheets, and plates of bone to form.
Spanning joints and joints, the stiff fabric gradually limits mobility, locking body parts in place and reducing the lifespan of those affected.
Not everyone with FOP has the same rate of calcification, but once bone is deposited in one part of the body, it is permanent. Most people need a wheelchair before the age of 20.
Unfortunately, today there is no treatment available for FOP, although the pain and swelling experienced by patients can be alleviated somewhat with medication.
Over the course of a patient’s lifetime, illness and physical trauma can cause flare-ups of muscle swelling and inflammation that can last for days or even months, often resulting in bone formation later on. If these events can be limited, the progression of the disorder may be blocked.
The recent long-term study is among the first to really dig into the progression of FOP in 114 patients. Previous studies of the one-in-a-million disorder were simply retrospective in nature or based on patient reports.
Only 33 people completed the full three-year study with regular check-ups (most left to participate in clinical tests for possible interventions). But in the end, the authors found that 82 patients (over 70% of the original cohort) reported 229 combined flare-ups, usually in the upper back, but also in the hip, shoulder, and lower spine. .
Twelve weeks after a flare-up, researchers often found that new bone had accumulated at the site of inflammation or pain.
Although the progression of FOP seems to slow with age, 70% of people aged 25 to 65 showed new bone volume during an annual health check-up.
The most common symptoms reported during these visits were severe pain, soft tissue swelling and very restricted movement.
“Findings from individuals receiving standard care for up to 3 years in this natural history study show the debilitating effect and progressive nature of FOP cross-sectionally and longitudinally, with greatest progression during childhood. and early adulthood,” the authors said. conclude.
The results reveal that the most common ongoing medications used by patients are nonsteroidal anti-inflammatory drugs. But over the course of the study, almost 80% of the participants started a new medication, suggesting they are desperately trying to find something that can help them feel better.
FOP doesn’t just impact the musculoskeletal system. Patients in the study typically suffered from respiratory problems, such as a reduced ability to expand the chest and hearing loss. The first can even be deadly.
Each of the participants showed an internal malformation in the growth of their big toes, which supports the idea that this could be one of the first signs of the disease. It is thought to be present from birth.
If physicians can stay on the lookout for this clear, early marker of FOP, then genetic testing could be done early to expedite diagnosis and possibly delay disease progression.
If diagnosis takes too long and the disease and its symptoms are not well managed, there is a greater chance that an injury, biopsy, muscle fatigue, or intramuscular injections can hasten soft tissue hardening.
A four-day course of high-dose corticosteroids during a flare has been shown to be quite effective in reducing inflammation associated with excessive bone development.
The new research in combination with ongoing clinical trialscould help improve the lives of people with FOP for years to come.
The study was published in Genetics in medicine.