Osteoarthritis is caused by a gradual breakdown of cartilage, the smooth tissue that cushions the ends of bones inside a joint. But it’s not simply “wear and tear” from aging. The process involves an active cycle of inflammation, failed repair, and structural changes across the entire joint, driven by a combination of mechanical stress, genetics, metabolism, and hormones. About 528 million people worldwide were living with osteoarthritis as of 2019, more than double the number in 1990, and roughly 73% of them are over 55.
How Cartilage Breaks Down
Healthy cartilage constantly rebuilds itself. The cells inside it (called chondrocytes) produce new structural proteins while enzymes clear away damaged material. In osteoarthritis, that balance tips. The enzymes responsible for breaking down cartilage become overactive, chewing through the structural fibers faster than the cells can replace them. Early on, chondrocytes try to compensate by ramping up production of new material. But as the disease progresses, the repair effort falls behind, and the cartilage thins and roughens.
The enzymes doing the damage belong to a family called matrix metalloproteinases. They come in several types: some dissolve collagen fibers, others break down the gel-like filler between those fibers, and a third group finishes the job by digesting the fragments. What makes this especially hard to reverse is that some of these enzymes activate each other in a chain reaction, creating a self-reinforcing loop of destruction.
A key driver of this loop is a signaling molecule called interleukin-1, one of the body’s inflammatory messengers. It pushes cartilage cells and the joint lining to produce more of those destructive enzymes while simultaneously blocking the production of new cartilage material. It also triggers cell death within the cartilage itself, further reducing the tissue’s ability to heal.
Mechanical Stress and Joint Injuries
Excess force on a joint is one of the most straightforward causes of osteoarthritis. Joints adapt to the loads placed on them, but when the demand consistently exceeds what the tissue can handle, the breakdown process accelerates. This is why osteoarthritis clusters in weight-bearing joints like knees and hips, and why carrying extra body weight significantly raises the risk.
A single major injury can also set the stage. Torn ligaments, meniscus tears, and fractures that extend into the joint surface all increase the likelihood of developing osteoarthritis in that joint later. The timeline varies enormously: some people develop symptoms within a year of the injury, while others remain symptom-free for 10 to 20 years before the damage becomes apparent. This post-traumatic form of osteoarthritis accounts for a meaningful share of cases, particularly in younger adults.
Occupational and Repetitive Stress
Certain jobs carry a measurably higher risk. Heavy physical workloads are the most consistently identified occupational risk factor, and the association shows up across multiple joint locations. Kneeling, regular stair climbing, crawling, bending, whole-body vibration (common in driving heavy equipment), and repetitive hand or arm movements all correlate with higher rates of localized osteoarthritis. Construction workers, farmers, floor layers, and people in manufacturing roles tend to develop joint problems in the specific areas their work stresses most.
The Role of Body Fat and Metabolism
For decades, doctors assumed that obesity caused osteoarthritis simply by putting more weight on joints. That’s part of the story, but it doesn’t explain why people with obesity also develop osteoarthritis in their hands, which bear no body weight at all. The missing piece is metabolic inflammation.
Fat tissue is not inert. It actively secretes signaling molecules, including a group called adipokines, that promote inflammation throughout the body. These molecules can reach joint tissue through the bloodstream and through local fat deposits near joints, like the fat pad behind the kneecap. Once there, they ramp up the same inflammatory signals that drive cartilage destruction. They also boost levels of several inflammatory messengers in the fluid inside the joint, infiltrate the cartilage directly, and activate the degenerative cascade. This means excess body fat attacks joints both mechanically (through load) and chemically (through inflammation), a combination that makes weight management one of the most effective strategies for slowing the disease.
Genetics and Family Risk
Osteoarthritis runs in families, and genetic factors account for a substantial portion of a person’s risk. Researchers have identified variations in several genes that influence how cartilage and bone develop, maintain themselves, and respond to stress. One well-studied example involves a gene called SMAD3, which plays a role in how cells communicate during tissue growth and repair. A specific variation in this gene raises the risk of both hip and knee osteoarthritis by about 22% in European populations.
No single gene causes osteoarthritis on its own. Instead, dozens of small genetic variations each nudge the risk up or down. Some affect the quality of cartilage a person is born with, others influence the intensity of inflammatory responses, and still others determine how efficiently the body repairs joint damage over time. If your parents or siblings developed osteoarthritis, your baseline risk is higher, though lifestyle factors still play a large role in whether and when the disease develops.
Why Women Are Affected More Often
About 60% of people with osteoarthritis are female, and the gender gap widens sharply after menopause. Several factors converge to explain this. Hormonal shifts appear to play a direct role: estrogen influences how cartilage cells function and how inflammatory pathways behave inside joints. During phases of higher estrogen (such as certain points in the menstrual cycle or pregnancy), joints become measurably looser, which may contribute to cumulative joint stress over time. When estrogen levels drop during menopause, the protective effects it provides to cartilage metabolism may diminish as well.
Weight gain during menopause adds a compounding factor. The metabolic and mechanical effects of added body weight layer on top of the hormonal changes, helping to explain the sharp increase in new osteoarthritis diagnoses among women in their 50s and 60s.
Changes Beyond Cartilage
Osteoarthritis is often described as a cartilage disease, but it reshapes the entire joint. The bone just beneath the cartilage (subchondral bone) thickens and stiffens as the disease progresses, a process called sclerosis. This happens because the bone actively remodels itself in response to altered loads, following the same principle that makes bones denser in areas of high stress. But the new bone formed in an osteoarthritic joint is structurally abnormal, denser but less resilient, which further compromises the joint’s ability to absorb shock.
Bone spurs (osteophytes) develop around the edges of the joint in later stages, growing as the body attempts to stabilize an increasingly damaged joint. These bony projections can restrict movement and press on nearby nerves, contributing to pain.
The synovium, a thin membrane that lines the inside of the joint and produces lubricating fluid, also becomes inflamed. This synovial inflammation is strongly linked to joint pain, particularly in early-stage disease, and contributes to further cartilage damage. Over time, chronic inflammation scars and thickens the synovium, impairing its ability to nourish the joint and support healing. The result is a cycle in which damage to any one part of the joint accelerates damage to the rest.