Scientists in Montreal have discovered a new genetic mutation linked to "bone death" or osteonecrosis of the hip, with the help of four young siblings who suffered from the debilitating disease.
Dr. Chantal Seguin, a hematologist-oncologist at the Research Institute at McGill University Health Centre, said three sisters and a brother were diagnosed in their 20s and 30s with osteonecrosis at the top of the femur.
"Four siblings out of six in the same family, and all of them had advanced disease on both hips," she said, adding patients can be as young as 10, and that the entire bone beneath the cartilage can "die" in some cases.
Seguin's path toward the discovery began about three and a half years ago when she saw a patient in her 30s at the Osteonecrosis Clinic at Montreal General Hospital.
She was diagnosed at age 21, but the disease had progressed to the point of extreme pain by the time Seguin intervened and later learned that three of the patient's siblings also had trouble with their hips.
Orthopedic surgeon Dr. Ed Harvey, who had worked at the clinic with Seguin for 18 years, helped diagnose the disease through X-rays and MRIs, eventually leading to identification of a gene called TRPV4.
Research on the gene, which plays a critical role in blood flow and bone development, has been published in the Journal of Medical Genetics.
Seguin said an intriguing aspect of the research is that the family is of European descent and that up to now, only one other such gene mutation had been identified in five Asian families.
However, the findings from the Asian families in 2005 have not led to early diagnosis or new treatments, she said, adding she is collaborating with two American experts on TRPV4 in hopes of developing early detection and targeted therapies for osteonecrosis patients.
Dimitra, who did not want her surname used, said her sister Eleni was the patient who saw Seguin three and a half years ago, setting off a study that led to the genetic mutation discovery.
She said Eleni suffered acute pain in her hips, starting at about age 19, and could sometimes barely stand.
About a decade later, Dimitra, now 43, also started having pain in her hips.
"I didn't think anything of it at the time but after I gave birth at 35, within a two- or three-year period I had pain all the time and I could barely make it through the day," she said.
"That's when I said to my sister, when I was actually having a lot of difficulty, I said, 'There's got to be a connection here.' My other siblings were also having a bit of trouble and that's how we all got involved with (the study)."
Dimitra had both hips replaced about three years ago.
"It was impossible to care for a five-year-old (daughter) at the time and be in constant pain," she said.
Dimitra said a treatment called core decompression was used to slow the progression of Eleni's disease.
Her brother, now 40, is managing his pain and has not yet had a hip replacement, and neither has another sister. She does not know if her parents, who are deceased and of Greek origin, had hip problems.
Dimitra said she's hoping further research could one day help her daughter and her children.
Seguin said she may take more DNA samples from Dimitra and her siblings to further her research.
"The next step is to try and find other families also in the world, of European descent and try to see if this mutation is seen worldwide."
Seguin said the discovery could help to better understand a much more common form of osteonecrosis that is induced by medications called glucocorticoids, or steroids, used as anti-inflammatories or in chemotherapy to treat blood cancer.
Seguin said she treated a 24-year-old patient who developed osteonecrosis after being prescribed the medication for leukemia.
The young woman, who is half Greek, has had both of her hips replaced.