It’s long been held that OA is a result of wear and tear on the joints, an inevitable consequence of years of use. But increasingly research is painting a far different picture – a disease resulting a complex interplay of multiple factors, including genes, body fat, trauma and, of course, aging. 

Here are some of the factors now known to be involved in osteoarthritis and what these findings could potentially mean for treatment. 

Genes

In 1990, the National Institutes of Health announced that scientists had isolated a gene responsible for osteoarthritis. The flawed gene is involved in making type II collagen, a key component of joint cartilage. In people with the gene mutation, weakened cartilage leads to a form of familial osteoarthritis that occurs in early adulthood.

Since that time, scientists have discovered that this type II collagen gene is not the gene responsible for osteoarthritis, but is likely just one of many – some which are not directly involved in joint cartilage, says Roland W. Moskowitz, MD, of Case Western Reserve University in Cleveland, one of two scientists making that first genetic discovery. 

For example, joint laxity in a condition called Ehlers-Danlos syndrome could lead to problems with the articular cartilage, resulting in secondary OA, as could certain genetic metabolic disorders such as hemochromatosis – a genetic disease in which too much iron builds up in the body – or calcium pyrophosphate dihydrate (CPPD) deposition disease, a condition in which CPPD, a calcium salt, builds up and the joints and forms irritating crystals.

Research shows genes also play a role in OA severity. Most recently, data from the Johnson County Osteoarthritis Project – which monitored 1,154 residents of the North Carolina county for up to 11 years – revealed nine genes associated with the progression of osteoarthritis. The strongest of the associations involved a pattern of variations in the gene for interleukin-1 receptor antagonist (IL-1RA), a cytokine associated with inflammation and cartilage breakdown, says Joanne M. Jordan, MD, director of the University of North Carolina’s Thurston Arthritis Research Center, who led the study.  Having the variations doubled the chance of a person’s OA progressing to a severe stage, she says. 

While similar findings have occurred in some other studies, not all have identified the same genetic variants to be associated with knee OA progression. Jordan says despite this, genetic findings may offer clues for understanding and treating the disease and help doctors identify patients whose disease should be treated more aggressively.