Arthritis in the knee develops when the cartilage, joint lining, or surrounding structures break down or become inflamed. The most common cause is osteoarthritis, a gradual wearing away of the cartilage that cushions the joint. But knee arthritis can also result from autoimmune disease, crystal deposits, past injuries, or a combination of risk factors that accumulate over years.
How Cartilage Breaks Down in Osteoarthritis
Healthy knee cartilage constantly rebuilds itself. Old tissue is broken down by enzymes while new tissue is laid down by cartilage cells called chondrocytes. In osteoarthritis, this balance tips toward destruction. Two families of enzymes do most of the damage: one type chews through collagen (the tough structural fiber in cartilage), and another strips away a spongy molecule called aggrecan that gives cartilage its ability to absorb shock.
The loss of aggrecan typically comes first and is considered reversible in the early stages. Once the collagen network starts to break apart, though, the damage becomes permanent. Normally, a natural inhibitor protein keeps both types of enzymes in check. In osteoarthritic joints, levels of that protein drop, not because the body stops making it, but because it gets cleared away too quickly. The result is enzymes running unchecked, steadily dissolving the cartilage surface. Aging cartilage cells, oxidative stress, and low-grade inflammation all accelerate this process.
Body Weight and Joint Force
The knee bears enormous loads. During normal walking, the force on your knee joint averages about 2.9 times your body weight. That means a person weighing 200 pounds puts roughly 580 pounds of force through each knee with every step. Running, climbing stairs, or squatting increases that multiplier further.
Excess weight is one of the strongest modifiable risk factors for knee arthritis. Globally, the disability caused by knee osteoarthritis linked to high body mass index nearly tripled between 1990 and 2021. Women bear a disproportionate share of this burden, with 1.8 times the disability of men. Projections suggest the global impact will nearly double again by 2050, driven largely by rising obesity rates in South Asia, East Asia, and Southeast Asia. Carrying extra weight doesn’t just increase mechanical stress. Fat tissue also produces inflammatory molecules that accelerate cartilage breakdown, so the effect is both mechanical and chemical.
Past Knee Injuries
A serious knee injury can set the stage for arthritis years or even decades later. Within 10 to 20 years of tearing an ACL or meniscus, roughly half of all patients show signs of osteoarthritis on X-rays. A large population-based study in the British Journal of Sports Medicine found that cruciate ligament injuries raised the absolute risk of developing knee osteoarthritis by about 20 percentage points compared to people without injuries. Meniscal tears raised it by about 10 percentage points. When both injuries occurred together, the risk increase was roughly 19 to 20 percentage points.
This happens because injuries alter the joint’s mechanics. A torn meniscus removes a shock absorber. A damaged ligament allows abnormal sliding and rotation. Even after surgical repair, the joint rarely returns to its original biomechanics, and the cartilage gradually wears in patterns it wasn’t designed for.
Knee Alignment
The angle of your leg affects which part of your knee wears fastest. Bow-legged alignment (varus) pushes more load onto the inner half of the knee. Knock-kneed alignment (valgus) shifts it to the outer half. In people who already have some osteoarthritis, bow-legged alignment increases the risk of the inner compartment getting worse by about 3.6 times. Knock-kneed alignment increases the risk of outer compartment progression by nearly 5 times.
Alignment can be inherited or develop gradually from cartilage loss itself, creating a feedback loop: arthritis causes malalignment, which accelerates more arthritis in the overloaded area.
Genetics
Your genes account for roughly 50% or more of your susceptibility to knee osteoarthritis. Twin studies in women estimated the genetic contribution to knee arthritis at 39% to 65%, independent of weight, age, and other environmental factors. Multiple genes are involved, including those that code for collagen types, cartilage proteins, growth factors, and hormone receptors. No single gene causes knee arthritis on its own, but inherited variations can make your cartilage structurally weaker, your inflammatory response more aggressive, or your repair mechanisms less efficient.
Occupational and Repetitive Stress
Jobs that demand heavy physical work significantly raise the odds of knee arthritis. A meta-analysis of 71 studies found that physically demanding occupations carried a 52% higher risk of knee osteoarthritis compared to sedentary jobs. The specific activities that matter most are kneeling, squatting, heavy lifting, climbing, and prolonged standing.
Agriculture workers, construction workers, floor layers, carpenters, metal workers, cleaners, and service workers all showed elevated risk. The common thread is repetitive compressive or shearing force on the knee over years. If your job keeps you on your knees or in a deep squat for hours a day, the cumulative load on your cartilage adds up in the same way that excess body weight does.
Rheumatoid Arthritis and Autoimmune Causes
Osteoarthritis is a wear-and-tear process, but rheumatoid arthritis attacks the knee from the inside out. It’s an autoimmune disease in which the immune system targets the synovial membrane, the thin lining that produces lubricating fluid inside the joint. Immune cells, especially macrophages, flood the lining and trigger intense inflammation. The number of macrophages in the synovial tissue correlates directly with how much bone erosion occurs over the following year.
This inflamed lining thickens and produces inflammatory signals, including interleukin-6, that spill into the joint fluid and eat away at both cartilage and bone. Unlike osteoarthritis, which tends to affect one knee more than the other, rheumatoid arthritis often strikes both knees symmetrically and can begin at any age. The joint damage is faster and more destructive if left untreated.
Crystal Deposits: Gout and Pseudogout
Two types of crystal arthritis commonly affect the knee. Gout occurs when uric acid crystals build up inside the joint, triggering sudden, severe inflammation. Pseudogout (also called calcium pyrophosphate deposition disease) involves a different crystal made of calcium pyrophosphate. Both conditions cause intense pain, swelling, and redness that can come on within hours.
The knee is actually the most common joint affected by pseudogout, while gout more famously targets the big toe but frequently involves the knee as well. Crystal arthritis episodes are episodic at first, but repeated flares can cause permanent cartilage and bone damage that looks similar to osteoarthritis on imaging.
Age, Sex, and Hormones
Age is the single biggest non-modifiable risk factor. Cartilage cells become less active and less responsive to repair signals as you get older. The water content of cartilage changes, making it stiffer and more brittle. Years of cumulative loading add up.
Women develop knee arthritis at higher rates than men, particularly after menopause. Estrogen appears to have a protective effect on cartilage, and its decline after menopause may partly explain the sharp rise in knee arthritis among women in their 50s and 60s. Women also tend to have wider hips relative to their knees, which changes the angle of force through the joint. The combination of hormonal shifts, alignment differences, and longer life expectancy means women carry a substantially greater share of the global knee arthritis burden.