A three-year study followed dozens of patients with an extremely rare disorder that gradually turns muscles, tendons and ligaments into bone.
The lifelong, irreversible condition is known as fibrodysplasia osteoplasia progressive (FOP). While estimates of its prevalence vary, confirmed cases occur in about one in 1 to 2 million births.
Only about 800 patients have been diagnosed with FOP worldwide, and in 2006, 97 percent of patients were found to have the same genetic variant of the disease.
This mutation, which occurs in a gene that codes for a receptor that regulates bone growth, appears to cause stem cells to produce bone tissue in places where it shouldn’t normally have it.
Given the severity and rarity of FOP, it is hoped that the findings of the current research will allow physicians to better respond to the medical needs of underserved patients.
Progressive soft tissue calcification from FOP is not constant. it comes in waves. Episodes usually begin in childhood and tend to start in the neck and shoulders, causing bands, sheets, and plates of bone to form.
By stretching joints and joints, the stiff tissue progressively limits mobility, locking body parts in place and shortening the lifespan of those affected.
Not all FOP sufferers experience the same rate of calcification, but once the bone is set in a part of the body, it is permanent. Most people need a wheelchair by age 20.
Unfortunately, currently, there are no treatments available for FOP, although the pain and swelling that patients experience can be somewhat relieved with medication.
During a patient’s lifetime, illness and physical trauma can cause flare-ups of muscle swelling and inflammation that can last days to months, often leading to bone formation afterward. If these events can be limited, there is a chance that the progression of the disorder will be stopped.
The recent long-term study is among the first to really delve into the progression of FOP among 114 patients. Previous studies of the one-in-a-million disorder have only been retrospective or based on patient reports.
Only 33 people completed the full three-year study with regular checkups (most stayed to participate in clinical trials of potential interventions). But ultimately, the authors found that 82 patients (more than 70 percent of the original cohort) reported a combined 229 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 appears to slow with age, 70 percent of people ages 25 to 65 developed a new bone tumor at an annual checkup in the study.
The most common symptoms reported during these visits were severe pain, soft tissue swelling, and very limited movement.
“Results from subjects receiving standard care for up to 3 years in this natural history study demonstrate the debilitating effect and progressive nature of FOP cross-sectionally and longitudinally, with greatest progression during childhood and early adulthood,” the authors conclude.
The findings reveal that the most common ongoing medication used by patients is non-steroidal anti-inflammatory drugs. But during the study, nearly 80 percent of the participants started a new drug, which suggests they are desperate to find something that can help them feel better.
FOP does not only affect the musculoskeletal system. Patients in the study were commonly found to suffer from breathing problems, such as reduced ability to expand the chest and hearing loss. The first can even be fatal.
Each of the participants showed inward growth of their big toes, which supports the idea that this may be one of the first signs of the disorder. It is thought to be present from birth.
If doctors can keep their eyes out for this clear and early indicator of FOP, then genetic testing could be done in time to speed diagnosis and possibly delay the progression of the disease.
If the diagnosis takes too long and the condition and its symptoms are not properly treated, there is a greater chance that injury, biopsy, muscle fatigue or intramuscular injections will accelerate the hardening of the soft tissues.
A four-day course of high-dose corticosteroids during a flare has been shown to be quite effective in reducing the inflammation associated with bone overgrowth.
The new research, combined with ongoing clinical trials, could help improve the lives of people with FOP in the years to come.
The study was published in Genetics in Medicine.