Could a new treatment mean new hope for brittle bone disease?


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Brittle bone disease, though relatively rare, affects tens of thousands of people in the U.S. The inherited condition can mean bone malformation, multiple fractures and restricted physical activity from birth and can, in some cases, lead to premature death. Now, researchers say, for those who cope with its debilitating effects, an unexpected beacon of hope may come from research into osteoporosis.


A growing problem

Research published by the University of Michigan in Ann Arbor suggests that a new drug designed to treat the devastating bone disease osteoporosis may also have a role in treating brittle bone disease — also called osteogenesis imperfect or OI — a rare genetic bone disorder that makes bones highly susceptible to breaks and fractures. In a healthy body, bone is built up and is regularly replaced as it gets older. Growth of too much new bone is prevented by a protein called sclerostin, which tells the bone-producing cells when enough is ADAM.comenough. This keeps the bones the right size, shape and density. In a body where there isn't enough healthy bone around, slowing down the job that sclerostin does becomes important — and that's where the new drug comes in. Previous studies have shown it to help with new bone growth in both mice and humans with osteoporosis.

"The dynamics of bone growth in young mice and in children are very different from those in adults," said Ken Kozloff, associate professor of orthopedic surgery and biomedical engineering. "Their bone structures are still forming, so it's important to understand how inhibiting sclerostin may affect that. We were also concerned that the benefits of the drug would reverse themselves after treatment stopped." The researchers say the results of their study are encouraging. In laboratory tests, no decrease in "midshaft" bone strength was detected even six weeks after treatment ended. Though some loss of new "spongy" bone was apparent, the scientists discovered the problem was rectifiable by combining the new drug with other therapies.



Boning up on the facts

So what's the difference? Well, for a start, says the National Institutes for Health (NIH), the term osteoporosis is "a general one, not related to any specific cause for the bone loss." There are many factors that can lead to osteoporosis — a number of them relate to physiology and nutrition. The NIH says that medication, lifestyle, gender, age and body size are all important aspects. Women, for example, are affected more than men — particularly after menopause. However, it can also be related to hormonal imbalance, family history and ethnicity — with Black and Hispanic women having a lower risk. As a result, cases of osteoporosis are far more common. According to the NIH, "in the United States, more than 40 million people either already have osteoporosis or are at high risk due to low bone mass."

Hope for brittle bone disease 

Brittle bone disease is a specific inherited disease. Healthline.com says it is "a genetic defect that affects the production and formation of type 1 collagen, a protein used to create bone. The defective gene is usually inherited, but in some cases the defect occurs due to a spontaneous mutation." The condition has eight distinct types that range from the relatively mild Type I where those affected can lead close to normal lives to the severe Type II which is "frequently lethal at or shortly after birth, often due to respiratory problems." As well as brittle bones, the disease can mean bone deformities, loose joints, weak teeth, discoloration of the eye, bowed legs and arms, abnormal curvature of the spine, hearing loss, respiratory problems and heart defects. The Osteogenesis Imperfecta Foundation reports that "while the number of people affected with OI in the United States is unknown, the best estimate suggests a minimum of 20,000 and possibly as many as 50,000." — that's about 1 in 20,000 live births.


A future framework

At this time, the team is working with studies on mice that have a genetic condition similar to OI and they will continue with these for another two years. However, there are hopes that they may soon be able to progress to small samples of bone cells taken from patients. Already, they say, the new drug is a significant improvement over current treatments, which only reduce the loss of existing bone. The disease limits the body's ability to make new bone meaning current treatments focus on reducing the rate of loss rather than replacing bone. In many cases, doctors prescribe "rodding" in which metal rods are surgically inserted to prevent fractures. The hope is that new, more effective treatments for patients will be available within five to six years.


"I envision a treatment that uses a precise combination of sclerostin antibodies to grow new bone, followed by bisphosphonates to lock in that bone growth," said Michelle Caird, associate professor of orthopedic surgery who specializes in brittle bone disease. "The rodent studies we're doing right now are giving us a better understanding of how to optimize the timing and amounts of the two drugs. We have years of hard work ahead of us, but I think this could really improve quality of life for kids with this disease."