09/29/09 A new study suggests that obesity, by itself, does not inevitably lead to the development of osteoarthritis (OA), a finding that challenges current theories about why joints fail.
Researchers at Duke University Medical Center, in Durham, N.C., studied strains of mice that were unable to make and respond to the hormone leptin, which controls appetite. The animals were given unlimited food and water, and with no brake on their hunger, these leptin-deficient mice quickly gained weight, becoming three times the weight of normal mice, with 10 times as much body fat.
“To our surprise, they didn’t get arthritis,” said Farshid Guilak, PhD, director of Duke’s Orthopaedic Bioengineering Laboratory. “That tells us that obesity in and of itself may not be the cause of osteoarthritis.”
Osteoarthritis develops when cartilage, the spongy, white tissue that buffers the ends of bones where they meet at the joints, fails and wears away, causing pain, swelling and stiffness.
Doctors have long noted that being overweight dramatically increases a person’s risk of developing osteoarthritis, though they aren’t sure why.
Some researchers argue that extra pounds exert mechanical forces on joints that they weren’t designed to handle, eventually destroying cartilage, while others blame the breakdown on inflammatory chemicals, including leptin, that are cranked out by fatty tissue.
The Duke study, which was funded by grants from the Arthritis Foundation and the National Institutes of Health, sought to separate the effects of the weight of excess body fat from the effects of the soup of inflammatory chemicals, chiefly leptin, that fat cells create.
The results, which are published in the October 2009 issue of the journal Arthritis & Rheumatism, suggest that the chemical effects of obesity play a strong roll in the development of osteoarthritis.
But the experiment has several limitations. Because even though the obese, leptin-deficient mice didn’t develop osteoarthritis, they also didn’t move around as much as the normal mice, which may have prevented their joints from being excessively stressed by their body weight, as human bodies are.
“They become highly sedentary,” Guilak says. “They sit on their bellies, and all they do is eat.”
“That’s another factor, and that’s really hard to test. Once they get this big, there’s really no way to get them to move,” he adds.
Still, Guilak thinks mechanical differences were probably not the determining factor.
He points to previous research that suggests obesity increases the risk for osteoarthritis in non-weight bearing joints, like the wrist and fingers, as well as loaded joints, like the knee. And other studies have found that leptin increases the activity of a protein that breaks down cartilage.
What’s more, when researchers tested levels of pro-inflammatory proteins in the leptin-deficient mice, they were almost the same as the normal mice, suggesting that despite their size, they were protected from that consequence of obesity, perhaps because shutting off leptin, which acts as a master hormone in the body, also turns off a further cascade of pro-inflammatory chemicals.
“It’s a good and important study,” says David Felson, MD, a professor of medicine and epidemiology at Boston University who is investigating how mechanical loading contributes to the development of osteoarthritis. But he adds, “I’m not sure it explains why humans get OA in their knees.”
Dr. Felson says he thinks the current study does help to explain the mystery of why obese people are more likely to get osteoarthritis in non-weight-bearing joints.
“I think we’ve been confused as to why hand osteoarthritis tends to occur in obese people if they’re not walking on their hands, and this helps to explain that,” Dr. Felson says.
But he says the effects of body weight can't be discounted.
For example, Dr. Felson says, it's true that obesity increases the risk of osteoarthritis in non-weight-bearing joints like the hand, but that risk is only slightly increased, by about 30 percent, compared to the risk increases for weight-bearing joints like the knee and hip, which skyrocket 400 to 1,000 percent.
“That’s almost certainly because of the mechanical effect of obesity,” Dr. Felson says.
Timothy Griffin, PhD, a researcher with the Oklahoma Medical Research Foundation, who was lead author on the study, says he believes that the development of osteoarthritis will prove to be an interaction between several different factors, including biomechanics, inflammation and possibly diet.
“I think we have a really neat system to start testing some of the ideas right now,” Griffin says of the leptin-deficient mice.
“We can’t do this in humans,” Guilak adds, “But the fact that you can separate [obesity from osteoarthritis] tells us that there may be pathways where we can interrupt osteoarthritis” perhaps, eventually, with new medications.
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