May 9, 2011

Surgery Strengthens Brittle Bones
By Carolyn Gutierrez
For The Record
Vol. 23 No. 9 P. 24

By implanting newly developed telescoping rods, surgeons can boost the quality of life for patients with osteogenesis imperfecta.

On his fourth birthday, a boy with severe osteogenesis imperfecta (OI), also known as brittle bone disease, was able to walk for the first time thanks to an innovative procedure in which rods were implanted into his thigh bones.

Ismael Vega had broken his legs 12 times and suffered more than 100 microfractures prior to the surgery. Because of OI, he had been unable to pull himself up without fracturing his small legs. Some physicians told his mother, Patricia, that he would probably never walk. But after learning about a specialized pediatric orthopedic surgery available in New York City, the Long Island mom realized there was an alternative for her son.

By implanting stainless steel telescoping rods into the leg bones, Daniel W. Green, MD, FAAP, an associate attending orthopedic surgeon at the Hospital for Special Surgery, was able to provide the support and stability the boy needed to take his first steps.

Characteristics and Symptoms
OI is an incurable genetic disorder characterized by a fragile, easily fractured skeletal system. Patients with OI may also have symptoms such as muscle weakness, scoliosis, blue sclerae (a bluish discoloration of the whites of the eyes), and brittle teeth. They are prone to fragile skin, short stature, loose joints, easy bruising, and frequent nosebleeds. Hearing loss, asthma, and other lung problems are common occurrences for both children and adults with OI.

Curved, misshapen bones are typical with OI. “Without surgical support, the bones are so weak that they not only break over and over, but when they heal, they heal in a crooked position. In a case like Ismael’s, by the time he was 3, one of his bones was actually bent at a right angle; it was actually bent 90 degrees,” notes Green.

OI is caused by a DNA mutation within the gene that controls collagen production in the bones. Deficient collagen or abnormalities in the collagen’s structure leave the bones extremely brittle and vulnerable to breakage. The severity of each case depends on the degree of the collagen defect. Genetic testing and collagen analysis can be helpful in diagnosing OI.

“It’s a genetic disease, but many of the children who have it, their parents don’t have it, so their disease is known as a spontaneous mutation,” says Green.

The range of OI’s severity is vast. The spectrum includes very mild manifestations of the disease that often go undiagnosed to patients who experience minimal fractures to those who have hundreds of fractures in their lifetime. “There are cases so severe where [the fetus] breaks its bones while in its mother’s uterus,” says Green. Newborns with the most severe forms of OI generally don’t live more than a few days.

Based on the manner of genetic inheritance, x-ray information, and overall health, OI patients are generally classified into a type system that was developed in 1979. The type system can be very fluid, however, as there can be subtle and unique differences in each patient’s disease, making classification of each patient difficult.

“There are some severe cases where we’ll do the surgeries, not with the hope that they can be a great walker, but with the hope that we can get them comfortable to get in and out of the wheelchair and sitting up without breaking their arms and legs all the time. It’s a complicated, diverse disease,” says Green.

Rodding Surgery
OI treatment depends on the severity of the disease and the patient’s age. Current treatments include casts, splints, or wraps for broken bones and braces to support unstable limbs. Physical therapy and carefully monitored exercise, particularly swimming, can be beneficial to patients with OI.

Rodding surgery has been performed on children with moderate to severe OI since the 1940s. The surgery involves placing a rod into the marrow cavity of large bones, usually either the femur (thigh bone) or the tibia (shin bone). Rods can also be implanted in the upper arm bones and the spine in cases that involve severe scoliosis.

Complications from rodding surgery include the chance of fractures when positioning the child during surgery, infection, rod migration, and mechanical failure of a rod. Patients can also be sensitive to the rodding material used.

There are two major rod types used in OI surgery: nontelescopic and telescopic. Although they come in a wide array of sizes, nontelescopic rods do not expand. They are generally used for children with very short, narrow bones. Telescopic rods are thin rods encased within larger hollow rods, ideally enabling the rods to lengthen as a child’s bone grows, minimizing the need for multiple replacement surgeries.

“Rods have been used in children with osteogenesis imperfecta for over 50 years, and each decade or so there’s been an improvement or a new device that’s available for use. One excellent option is the telescoping rod that we used in Ismael’s case: the Fassier-Duval rod,” says Green.

Approved by the FDA in 2005, the Fassier-Duval model is the most advanced telescopic rod being used by pediatric orthopedic surgeons. Developed by François Fassier, MD, chief of staff at Shriners Hospitals for Children in Montreal, Canada, the new telescoping rod was created to minimize complications in OI surgery. Upgrading the design of previous rods, the Fassier-Duval version was developed with distinct criteria: to allow smooth expansion within the bones of a growing child, minimize migration of the rod within the bone, prevent damage to the growth plates and joints, and decrease scarring.

Its design fosters a less invasive surgery, resulting in a more rapid recovery compared with previous rod models. Smaller incisions are needed, plus there is less blood loss, only minimal soft tissue damage, and the joints do not need to be opened.

When utilizing the older rods, “You had to open up the knee to put them in, so there was more potential damage to the knee,” notes Green. “The Fassier-Duval rods can be put in from one insertion point at the hip. They also have some screw threads on the tips of each side so they’re a little more stable.”

At a May 2010 meeting of the Pediatric Orthopedic Society of North America, the results of a study were released showing the Fassier-Duval rod to be a reliable option for children with OI, with a lower reoperation rate compared with previous rods. Other studies have demonstrated the rod’s ability to improve children’s gross motor function. When implanted early, the rods can dramatically improve a child’s quality of life, including the possibility of walking.

After the rods are implanted, orthopedic physicians use x-rays to monitor the child’s growth for several years.

“Technically,” says Green, “our hope is to provide windows where the children don’t need surgery for two, three, four, five years. At some point, they will most likely need to have additional surgery—revision of the rods or replacement for a bigger rod when they grow. Sometimes there will be a complication caused by a fall or a trauma. If you follow the children for five years, at least 30% of the rods will have to be revised either because there’s been too much growth or the rods themselves are getting weak or the kids fall and the rods bend or the bones break around the rods. These children still have to be followed very closely.”

Because of the newer technology, rodding surgery is becoming an earlier treatment option. “Once the child’s muscle strength is strong enough where you can see the child wants to stand up in the crib, that’s when we’ll start to consider the child for surgery,” says Green. “The procedure’s been done on kids as young as 11/2 but probably the average is two or three for their first surgery.”

Bisphosphonate Medicines
Another important factor in treating OI is the use of bisphosphonates, a group of carbon-substituted analogs of pyrophosphate that give the affected bones much-needed resiliency. The same class of medicines that help patients with osteoporosis, bisphosphonates have been proven effective in strengthening the bone density and strength of patients with OI. Infants born with severe cases of OI are now routinely put on bisphosphonates shortly after birth to decrease the frequency of fractures, lessen pain, and increase bone strength.

“Just a few years ago, we weren’t sure if these bisphosphonate medicines were working well in children. Now, a number of studies have confirmed that bisphosphonates work in young kids,” says Green. “I first started training in the Hospital for Special Surgery in 1991 and that was before bisphosphonates were available and it was before the development of the Fassier-Duval rod. The younger children who have the benefit of both of those interventions seem to be doing a lot better than the kids who were growing up 20 years ago.”

Future Developments
When discussing future OI care, Green says there’s a group being overlooked. “We need to get better solutions for adult patients,” he says. “There are patients who are 60 years old with this disease. We have a paucity of data concerning how to help the adults with OI. There’s a need for specialized implants for them.”

Green would also like to see a more aggressive approach to OI. “There’s a lot to be learned about the disease and, on the horizon, there could even be genetic interventions and stem-cell therapy. What we’re doing right now is just treating the symptoms of the disease, and there’s a lot of work to be done to try to develop a cure,” he says.

Funding
Now 6 years old, Ismael has enjoyed visits to the beach and Disney World with the help of a small walker. His supportive family members have become great advocates for the OI cause.

In March, Ismael, his mother, and Green took a trip to Washington, D.C., on behalf of the Pediatric Society of North America to address Congress at the 2011 Research Capitol Hill Days event sponsored by the American Academy of Orthopaedic Surgeons. The gathering included more than 60 orthopedic patients, surgeons, and researchers who personally addressed senators and representatives on the need for funding more life-changing musculoskeletal treatments and surgeries such as Ismael’s.

Part of the trip’s purpose was to acknowledge the work of the National Institutes of Health (NIH), which paid for Ismael’s groundbreaking surgery.

“Ismael and I were asked to go down to the National Institutes of Health and to the Capitol to meet with members of our New York Congress and let the legislators know about the great work that the NIH is doing in this area,” says Green. “I think that because of the medicines and the surgical advancements, hundreds of patients with this rare disease wouldn’t have benefited with an improved quality of life and function had the government not invested in it. It’s a success story, and obviously we’re promoting additional research for the National Institute of Arthritis and Musculoskeletal and Skin Diseases [NIAMS].”

The NIAMS, part of the NIH, comprises about 2% of the total NIH budget. Orthopedic surgeons such as Green are hoping to see an increase in funding. According to the American Academy of Orthopedic Surgeons’ website, during the Capitol Hill event, “Patients, physicians, and researchers urged Congress to appropriate $556 million in fiscal year 2012 for the NIAMS—a 3.2% increase over fiscal year 2010.”

Although there is no cure at this time, many people with severe OI can lead satisfying and productive lives thanks to research and advances in technology. The most challenging time for a patient with OI may be in their youth, when they must carefully and patiently learn how to navigate through life with this rare disease and to not let their bones—or spirit—be broken.

— Carolyn Gutierrez is a freelance writer based in New York City.