Osteoarthritis (OA) is a leading cause of pain and disability among adults — and has doubled in prevalence over the past 70 years. Current numbers from the Arthritis Foundation tell it all:
- 54 million adults in the U.S. have physician-diagnosed arthritis
- By 2040, that number is expected to rise to 78.4 million
- Among people over 65, one in two men is likely to have arthritis, as are two in three women
- Arthritis is the leading cause of disability among adults in the U.S.
- In 2013, medical costs and earning losses totaled $304 billion
A major challenge today in OA is understanding the disease, why its prevalence has increased so markedly — and what can be done to halt this trend.
Pain and the Joint
Despite these alarming figures, few effective treatments for OA exist, and there are no approved disease-modifying drugs that can help prevent progression.
Recent years have seen a shift in the understanding of OA, which was once considered a disease of wear-and-tear associated with aging. Today, however, increasing evidence exists indicating that low-grade inflammation is a contributing factor and that the condition is a disorder of the whole joint. Pain, which in OA is exacerbated by activity, is what usually leads patients to seek medical care. However, there is considerable discordance between the pain experienced by patients and the structural pathology.
“The signature feature of OA is cartilage loss, but the disease is a lot more than that — it winds up affecting all structures of the joint and causing lots of pain in ways we really don’t understand very well,” said David T. Felson, MD, of Boston University School of Medicine, in an interview.
Excess body fat clearly contributes to the development of OA, with mechanical excess loading affecting the weight-bearing joints but also through the production and proliferation of pro-inflammatory cytokines such as tumor necrosis factor, interleukin (IL)-6, and IL-1 by adipose tissue.
A Mismatch Disease
A novel study led by Daniel E. Lieberman, PhD, chair of the department of human evolutionary biology at Harvard University in Boston, suggested that viewing OA in an evolutionary context could shed light on its changing prevalence and risk factors. He defined OA as a “mismatch disease.”
“A mismatch disease is either more common or more severe today because our bodies are inadequately or imperfectly adapted to novel environmental conditions,” Lieberman told MedPage Today.
“The concept of mismatching is not unusual in biology — species are constantly being exposed to changes in the environment, and natural selection is always acting on mismatches. But what’s happening now is that we are changing our world so fast and so powerfully through cultural evolution that mismatches are becoming more common,” he explained.
The contributions of increased longevity and obesity became accepted as primary drivers of the recent increase in OA, but this hypothesis had never been fully tested. So Lieberman and colleagues conducted a study in which they compared rates of late-stage knee OA in postindustrial individuals (late 20th and early 21st centuries) with rates in the early industrial era (19th to early 20th centuries), and also in archaeological skeletons of prehistoric Native American hunter gatherers and farmers (approximately 2000 BC to 1700 AD).
The postindustrial group included 819 individuals who died between 1976 and 2015 in Albuquerque and Knoxville, while the early industrial group consisted of 1,581 people who died from 1905 to 1940 in St. Louis and Cleveland. The prehistoric group included 176 skeletons from archaeological sites throughout the U.S. who were estimated to be ages ≥50 at the time of death. Late-stage knee OA can be identified in skeletal remains because of a pathologic process known as eburnation, a sclerotic polishing of subchondral bone resulting from bone-on-bone contact following loss of cartilage in the knee joint.
‘Astonishing’ Results
When the researchers compared the rates of knee OA in the three groups, the results were “astonishing,” according to Lieberman. After controlling for age and sex, the prevalence in the postindustrial group was 16% (95% CI 14%-19%), which was 2.6 times higher than in the early industrial sample (6%, 95% CI 5%-7%, P<0.001) and twice as high as in the prehistoric group (8%, 95% CI 5%-13%).
In addition, among the postindustrial patients with OA, 42% had both knees affected, which was a rate 2.5-fold higher than in the prehistoric group (17%, P=0.042) and 1.4-fold higher than in the early industrial group (30%, P=0.058).
At the time of death, individuals in the postindustrial group were 6 years older than the early industrial individuals, and their BMI was 41% higher. In the early industrial group, only 1% were obese and 6% were overweight, compared with 25% and 24%, respectively, of those in the postindustrial group (P<0.001).
Yet after adjusting for age and BMI, the prevalence of knee OA in the postindustrial sample (11%, 95% CI 8%-14%) was still 2.1 times higher than in the early industrial group (5%, 95% CI 4%-7%, P<0.01), Lieberman and colleagues reported in Proceedings of the National Academy of Sciences.
“These data show that knee OA long existed at low frequencies, but since the mid-20th century, knee OA has approximately doubled in prevalence, even after accounting for the effects of age and BMI,” they wrote.
Other factors that may have contributed, they proposed, include walking on hard pavements and in certain types of shoes, modern diets that include highly refined carbohydrates, and, in particular, lower physical activity, which is associated with thinner cartilage and lower cartilage proteoglycan content and is far more common today than in the past.
“From an evolutionary perspective, knee OA thus fits the criteria of a mismatch disease that is more prevalent or severe because our bodies are inadequately or imperfectly adapted to modern environments. Intriguingly, other well-studied mismatch diseases such as hypertension, atherosclerotic heart disease, and type 2 diabetes, that also have become epidemic during the last few decades are strongly associated with knee OA,” the researchers observed.
“There needs to be a large shift in how we think about these diseases of aging,” Lieberman said in an interview. “We are conflating diseases that are caused by aging with diseases that occur more commonly as you age. That’s a very serious conflation that we should stop doing.”
The focus should not be exclusively on treating OA, which is a highly debilitating disease with no cure apart from replacing the joint. “I’m not saying we shouldn’t treat people with OA. Obviously we should, but we also need to really think about how to prevent the disease. We’re not doing that right now, and that’s where an evolutionary perspective can really help,” he concluded.
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