Tuesday 5 February 2013

From the Archives: "Story on Bisphosphonate therapy" (1999)



This is a feature story assignment I wrote while I was a journalism student at Ryerson University 14 years ago. My Newspaper/Print professor liked it and gave it a high grade. We even talked about getting it published in one of the major newspapers or magazines. Unfortunately this didn't happen because I ended up losing the work, or so I thought at the time. This weekend I found it again while going through old items in my apartment. Now I want to share this story with everybody. Though some of the participants may not be involved with this treatment today, the content remains relevant and timely. - DB

Story on Bisphosphonate therapy (1999)
Donald Barrie

Carlos Medina is a happy six-year-old, but unlike most children his age, his bones break easily. Carlos was born with osteogenesis imperfecta, or brittle bone disease, which affects about one in nearly 20,000 children born each year. In addition to frequent fractures, it causes progressive deformities of the arms and legs, and chronic bone pain. Lately, however, Carlos has been feeling stronger physically, thanks to bisphosphonate therapy.

Bisphosphonates are a group of synthetic compounds that are most widely used in the treatment of post-menopausal osteoporosis. They reduce bone turnover and suppresses bone resorption (a normal breakdown process that is excessive in some diseases including osteoporosis and OI). The most common bisphosphonates being administered to these children with OI is pamidronate, which is closely related to alendronate (Fosamax), used to treat osteoporosis in adults.

At Sunny View Public School in Toronto, physiotherapist Lynn Mueller takes Carlos out of his electric wheelchair and puts him on the floor. Mueller, skeptical of his mother’s claims about his increased mobility, asks him to crawl on the floor. Lying on his back, Carlos turns over on his stomach, and crawls gently on his hands and knees. Carlos then pushes himself off the ground, and sits in a kneeling position.

Mueller’s eyes light up, and so do those of the kids looking on. Another therapist watching him from a distance rushes to get her camera. “I can’t believe it!” the two therapists exclaim. “This is the first time I have seen him do that!” Mueller adds ecstatically.

“When Carlos arrived at Sunny View, he was very weak,” Mueller says. “Since the start of this school year, he has gotten stronger, and his mobility has improved. However, he has only been doing the treatment since August, and sometimes he gets too brave.” She notes that Carlos recently suffered a skull fracture when he tried to get off the toilet on his own.

“I feel less pain now since I started the therapy,” he says, as he gently touches the small bump on the left side of his head where he had the skull fracture. “It still hurts a little though. If I was not doing the drug treatment, it would probably hurt more.”

Prior to taking this drug, Carlos was unable to crawl or sit up on his own, and would get fractures at least every one or two months. Now he can use a walker in therapy, and he can grip a pencil more securely when writing.

Bisphosphonate therapy is still at the experimental stage in the treatment of OI. Carlos is receiving treatment as part of a research project being conducted by Dr. Francis Glorieux and colleagues at the Shriners Hospital in Montreal.

Last October, the New England Journal of Medicine (NEJM) published results of their initial findings, arising out of an uncontrolled observational study on bisphosphonate therapy. The study, one of the first to investigate the use of bisphosphonates in this patient group, involved 30 children who were three to 16 years old and had severe osteogenesis imperfecta. The children were administered the drug pamidronate intravenously. The results of the study found that chronic bone pain decreased, motor function improved, bone mineral density increased, and bone resorption decreased.

Dr. Glorieux has extended the study of the effect of pamindronate to other children with OI. “We are currently following more than 170 patients suffering different types of OI,” Dr. Glorieux says. “It includes all the departments involved in the care of patients with OI. [We] aim to respond to all their needs, not only the medical management of their condition.”

As director of research at Montreal’s Shriners Hospital and professor of surgery, human genetics and pediatrics at McGill University, Dr. Glorieux has treated people with OI for the past 25 years. He found other medical treatments for OI unsuccessful, so he turned to bisphosphonates after seeing their effects in animal studies and in adults with osteoporosis.

The main concern against the use of these drugs in children was that it could affect growth. So he started treating very severe patients for whom height was not an issue. He discovered that growth was not arrested.

When a person like Carlos goes to Montreal for the treatment, it is for a three-day period every four months. During his first visit, the doctors made a small cut inn his hip to get a sampling of his bone structure. For the next three days, Carlos had pamidronate taken intravenously for six to eight hours each day.

Dr. Horacio Plotkin, one of Dr. Glorieux’s colleagues and co-author of the report in the NEJM, said in a phone interview from Montreal that the only side effect to pamidronate found is an “acute phase reaction.” It is a flu-like syndrome patients often experience the first time they receive the drug. This reaction resolves in 24 hours, and usually does not reappear with new infusions.

There are no other similar treatment facilities in Canada. Dr. William Cole, chief of Orthopedic Surgery at Toronto’s Hospital for Sick Children, says he is supportive of Dr. Glorieux’s study, and has referred patients to him. At this time, however, there are no plans to open a similar treatment facility in Toronto, as the treatment is still experimental. The Shriners Hospitals in Los Angeles and in Springfield (Massachusetts) are providing the treatment to selected cases.

Since Dr. Glorieux began his bisphosphonate therapy clinic in 1992, OI children from the United States, France, Brazil and Kuwait have come to Montreal for the procedure once every four months.

“There is no plan to end the study. All patients are improving, so we do not want to discontinue the treatment,” Dr. Plotkin explains.

The long-term benefits of bisphosphonate therapy are not known, and the knowledge of side effects is limited to seven years at the Montreal clinic. “It is probably the only treatment so far that is able to produce significant and positive changes in the quality of life of the patients,” says Dr. Plotkin, currently co-chair of the Pediatric Committee of the American Society of Bone and Mineral Research. “It is not the ideal treatment, and active research is taking place to find better treatments. Currently, we are only accepting patients under four years of age in Montreal, due to the overwhelming demand.”

As a 25-year-old adult with OI, I expressed personal interest in bisphosphonate therapy to Dr. Plotkin. But he cautioned me that bisphosphonate therapy may be less effective for anyone whose bones have stopped growing. Alendronate would be most appropriate for adults with OI, according to Dr. Plotkin.

At present, there are no reports that confirm the benefits of bisphosphonate therapy for adults with OI. In the long term, Dr. Plotkin believes it could help strengthen bones and reduce the likelihood of recurrent fractures later in life, when bone loss occurs with age. One serious side effect of alendronate is that it may cause esophagitis (i.e. an inflammation of the esophagus).

Both Dr. Glorieux’s paper and the editorial commentary in the NEJM make clear that bisphosphonate therapy is not a cure for OI. It reduces the rate of fractures, and improves bone mineral density as seen on X-rays. According to the editorial commentator in the NEJM, this treatment provides cause for cautious optimism. It strengthens the bones, but may not enable the more severely affected patients to walk. For some patients, walking is not their primary concern.

“[Dr. Glorieux] seemed to be so determined that I would walk and that’s not a big priority for me. It took a while for them to understand that,” insists Kristin Hayes, a 15-year-old who has been having bisphosphonate therapy since 1997. “I wanna get stronger but walking [to me] is not that important… After my first two treatments, my swimming coach noticed my endurance ad speed had suddenly improved, and, of course, bone density improved.”

As she hadn’t had bone pain or a fracture for four years before starting the treatment, the effects were less dramatic than those seen in younger, more severely affected patients.

In Dr. Plotkin’s view, bisphosphonate therapy has opened the door for new treatments, has increased the interest of the medical community in the disease, and he hopes it will lead to a change in the lives of patients with OI.

It has already given hope and strength to Carlos and his mother Eusemia, who feels more confident knowing her son is benefiting from the treatment. “The doctors told us that we could stop the treatment at any time, but we will keep going with it, because it is making his bones stronger,” she says as Carlos sits in his chair watching television at home after a long school day. “Carlos has become so confident since starting the therapy that he thinks he can do anything. He is not strong enough yet to walk on his own, but the doctors said someday that may happen.”

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