Knee osteoarthritis develops when the cartilage cushioning the joint breaks down faster than the body can repair it. This isn’t a single event but a gradual process driven by a combination of mechanical wear, biological inflammation, genetics, and aging. Roughly 535 out of every 100,000 people worldwide develop osteoarthritis each year, and the knee is one of the most commonly affected joints.
How Cartilage Breaks Down
Healthy cartilage maintains itself through a constant cycle of breakdown and rebuilding. Cells called chondrocytes produce the proteins that give cartilage its structure and shock-absorbing ability, while enzymes clear away damaged material. In a healthy knee, these two processes stay in balance.
In osteoarthritis, the enzymes responsible for breaking down cartilage become overactive. They chew through the structural proteins (collagen and proteoglycans) faster than chondrocytes can replace them. At first, the cartilage cells try to compensate. They multiply and ramp up production. But as the disease progresses, this repair effort falls behind, and the cartilage thins out.
What makes this worse is a feedback loop. Some of the overactive enzymes can activate even more enzymes, accelerating the destruction. At the same time, inflammatory signaling molecules suppress the production of new cartilage proteins and trigger cartilage cell death. The result is a cycle where damage fuels more damage, and the joint’s built-in repair system gets progressively overwhelmed.
Body Weight and Joint Force
Excess weight is one of the strongest modifiable risk factors for knee osteoarthritis, and the math explains why. Walking on flat ground puts force equal to about 1.5 times your body weight on each knee. Going up or down stairs increases that to two to three times your body weight. Squatting to pick something up off the floor loads each knee with four to five times your body weight.
For someone who weighs 200 pounds, that means each knee absorbs up to 1,000 pounds of force during a simple squat. Every extra 10 pounds you carry translates to an additional 40 to 50 pounds of pressure on the joint during everyday movements. Over years and decades, that extra load accelerates cartilage wear in the parts of the knee that bear the most weight.
Weight also contributes through inflammation. Fat tissue produces inflammatory molecules that circulate through the body, and these same molecules promote cartilage breakdown. This is why obesity increases the risk of osteoarthritis even in non-weight-bearing joints like the hands.
Prior Knee Injuries
A major knee injury dramatically raises the odds of developing osteoarthritis later, even if the injury heals well. A torn ACL (the ligament that stabilizes the knee front-to-back) is associated with a four-fold increase in osteoarthritis risk. A torn meniscus, the rubbery disc that cushions the joint, carries a six-fold increase. When both structures are damaged in the same injury, the risk climbs to seven times that of an uninjured knee.
This happens for several reasons. Injury triggers inflammation inside the joint that can persist long after the initial trauma heals. Surgery to repair the damage, while necessary, changes the joint’s mechanics in subtle ways. And a torn meniscus, even a repaired one, doesn’t distribute load as evenly as an intact one, concentrating pressure on certain areas of cartilage. Many people who tear an ACL in their 20s or 30s begin showing signs of osteoarthritis within 10 to 15 years.
Aging and “Zombie” Cells
Age is the single biggest risk factor for knee osteoarthritis, and the reason goes deeper than simple wear and tear. As you age, some cartilage cells stop dividing and functioning normally but don’t die. These senescent cells, sometimes called “zombie cells,” sit in the joint and cause problems. Instead of producing healthy cartilage, they release a cocktail of inflammatory molecules and the same cartilage-destroying enzymes that drive osteoarthritis.
The accumulation of these dysfunctional cells essentially turns part of the cartilage’s own cell population against it. They increase local inflammation, break down the surrounding matrix, and suppress the activity of remaining healthy cells. This is one reason osteoarthritis becomes so much more common after age 50: the ratio of functional to dysfunctional cells in the cartilage shifts steadily in the wrong direction.
Genetic Predisposition
Some people are genetically more vulnerable to knee osteoarthritis regardless of their weight or activity level. Researchers have identified variations in a gene called GDF5, which plays a key role in forming cartilage, tendons, ligaments, and the joint structures themselves. Certain versions of this gene reduce how actively it works, resulting in cartilage that may be structurally weaker from the start. People who carry these variants are overrepresented among osteoarthritis patients. Other versions of the same gene appear protective against knee osteoarthritis.
Genetics likely explain why osteoarthritis sometimes runs in families and why some people develop severe disease while others with similar risk factors do not. Your genes don’t guarantee you’ll develop the condition, but they can set the stage by influencing cartilage quality, joint shape, and how aggressively your body’s inflammatory responses behave.
Occupational and Repetitive Stress
Jobs that require frequent kneeling, squatting, heavy lifting, or walking long distances significantly increase knee osteoarthritis risk. Workers who regularly kneel or squat, walk more than two miles a day on the job, or routinely lift loads of 55 pounds or more show higher rates of the disease, even after accounting for body weight and prior injuries.
The risk compounds when physical job demands overlap with other factors. People with a BMI of 30 or higher whose work also requires prolonged kneeling and squatting face a particularly elevated risk. This combination subjects already-stressed cartilage to repeated high-force loading in positions that concentrate pressure on specific areas of the joint. Flooring installers, construction workers, farmers, and warehouse workers are among the occupations most studied for this link.
What Happens Beyond Cartilage
Osteoarthritis isn’t just a cartilage problem. As the disease progresses, the bone underneath the cartilage (called subchondral bone) begins to change. X-rays typically show increased bone density beneath the weight-bearing surfaces of the joint, a process called subchondral sclerosis. The bone essentially thickens and stiffens in response to abnormal loading, which paradoxically makes it worse at absorbing shock and transmits more force back into the remaining cartilage.
Other bone changes include the formation of bone spurs (osteophytes) around the joint edges, small fluid-filled cysts within the bone, and areas of bone marrow swelling visible on MRI. These bone marrow lesions are associated with increased pain and are a sign of excessive mechanical stress. Together, these changes alter the joint’s shape and mechanics, creating a new set of forces that accelerate cartilage loss in a vicious cycle. By the time most people feel significant knee pain, the disease involves not just thinning cartilage but remodeled bone, inflamed joint lining, and weakened surrounding muscles.
Multiple Causes, One Disease
Knee osteoarthritis rarely has a single cause. In most people, it develops from several overlapping factors. Someone with a genetic predisposition who also carries extra weight and had a sports injury decades ago faces compounding risks that together push the joint past its ability to maintain itself. Women develop knee osteoarthritis at higher rates than men, particularly after menopause, suggesting hormonal factors also play a role in cartilage maintenance.
The factors you can influence, body weight, activity patterns, injury prevention, and muscle strength around the knee, are also the ones that matter most for slowing the process down. Reducing body weight by even a modest amount meaningfully decreases the force your knees absorb with every step, and strengthening the muscles around the joint helps distribute load more evenly across the cartilage surface.