The arthritic Bullwinkles got that way because of poor nutrition early in life, an extraordinary 50-year research project has discovered. That could mean, scientists say, that some people's arthritis can be linked in part to nutritional deficits, in the womb and possibly throughout childhood.
The moose conclusion bolsters a small but growing body of research connecting early development to chronic conditions like osteoarthritis, which currently affects 27 million Americans, up from 21 million in 1990.
Osteoarthritis's exact cause remains unknown, but it is generally thought to stem from aging and wear and tear on joints, exacerbated for some by genes. Overweight or obese people have greater arthritis risk, usually attributed to the load their joints carry, and the number of cases is increasing as people live longer and weigh more.
But the moose work, along with some human research, suggests arthritis's origins are more complex, probably influenced by early exposures to nutrients and other factors while our bodies are developing. Even obesity's link to arthritis probably goes beyond extra pounds, experts say, to include the impact on the body of eating the wrong things.
Nutrients, experts say, might influence composition or shape of bones, joints or cartilage. Nutrition might also affect hormones, the likelihood of later inflammation or oxidative stress, even how a genetic predisposition for arthritis is expressed or suppressed.
"It makes perfect sense," said Dr. Joanne Jordan, director of the Thurston Arthritis Research Center at the University of North Carolina. "Osteoarthritis starts way before the person knows it, way before their knee hurts or their hand hurts. It's very clear that we're going to have to start looking back" at "things in the early life course."
Such research could lead to nutritional steps people can take to protect against osteoarthritis, a condition that is often painful or debilitating, and according to federal data, costs billions of dollars annually in knee and hip replacements alone.
"It would be helpful to know if we want to make sure pregnant moms are taking certain vitamins or if you need to supplement with such and such nutrition," said Dr. David Felson, an arthritis expert at Boston University School of Medicine. "The moose guy is right in that we probably should study weight or some other nutritional factor almost through adolescence when the bones or joints have stopped forming."
The "moose guy" is Rolf Peterson, a Michigan Technological University scientist on the Isle Royale project, which began in 1958 and is reportedly the longest-running predator-prey study.
For half the year, Dr. Peterson and his colleagues are the only humans allowed on the 45-mile-long island, part of a national park. They stay in yurts, a log cabin or a wood-stove-heated lodge, navigate the wilderness without roads or cars, and share a single staticky phone line. They analyze everything from wolves' moose-hunting strategies to moose feces. Collecting bones of more than 4,000 moose, they noticed that out of 1,200 carcasses they analyzed, more than half had arthritis, virtually identical to the human kind. It usually attacked the hip and instantly made the moose vulnerable.
"Arthritis is a death sentence around here — you need all four legs," Dr. Peterson said. "Wolves pick them off so quickly that you don't even see them limping."
What is more, the arthritic moose were often small, measured by the length of the metatarsal bone in the foot. Small metatarsals indicate poor early nutrition, and scientists determined that the arthritic moose were born during times when food was scarce, so their mothers could not produce enough milk.
Dr. Peterson said if the arthritis were caused by excess wear and tear on the moose's joints, that would have meant that times of food scarcity occurred when the moose were already grown, since the extra wear would have happened to moose walking farther to find edible plants. But the arthritic moose had had plentiful food as adults.
For people, several historical cases may suggest a nutritional link. Bones of 16th-century American Indians in Florida and Georgia showed significant increases in osteoarthritis after Spanish missionaries arrived and tribes adopted farming, increasing their workload but also shifting their diet from fish and wild plants to corn, which "lacks a couple of essential amino acids and is iron deficient," said Clark Larsen, an Ohio State University anthropologist collaborating with Dr. Peterson. Many children and young adults were smaller and died earlier, Dr. Larsen said, and similar patterns occurred when an earlier American Indian population in the Midwest began farming maize.
British scientists studying people born in the 1940s found low birth weight (indicating poor prenatal nutrition) linked to osteoarthritis in the men's hands, Dr. Felson said. And Dr. David Barker, a British expert on how nutrition and early development influence cardiac and other conditions, said "studies of people in utero during the Great Chinese Famine" of the late 1950s found that "40, 50 years later, those people have got disabilities."
Overeating can be as problematic as undereating. Dr. Lisa A. Fortier, a large-animal orthopedist at Cornell University's College of Veterinary Medicine, said she saw "abnormal joint and tendon development from excessive nutrition" in horses overfed "in utero or in the postnatal life," probably ingesting "too much of the wrong type of sugar that may cause levels of inflammation."
Dr. Peter Bales, an orthopedic surgeon affiliated with University of California, Davis, Medical Center, who has written about nutrition and arthritis, sees similar problems in overweight patients. He said the causes were not as "simplistic" as "carrying more weight around," but might involve nutritional imbalances that could hurt joints and erode cartilage. Much is unknown about nutrition's relevance. Isle Royale moose, for example, also seem to have genetic predispositions for arthritis, suggesting that nutrition might be amplifying or jump-starting the genes.
"Genes are not Stalinist dictators," said Dr. Barker, now at Oregon Health and Science University. "What they do, how they're expressed, is conditional on the rest of the body. The human being is a product of a general recipe, and the specific nutrients you get or don't get."
Studying nutrition in people is much more complicated than in moose. Dr. Peterson said the early moosehood developmental window occurred in utero through 28 months, but humans' developmental time frame lasted into the teens. Some experts say prenatal nutrition is most critical; others see roles for nutrients after birth and beyond.
"Up until the growth plates close, which is through adolescence and even early adulthood, the effects of nutrition are magnified," said Dr. Constance R. Chu, director of the Cartilage Restoration Center at the University of Pittsburgh, who said nutrients might affect the number of healthy cells in cartilage and its thickness. "But in my opinion, it's relevant throughout life."