Osteoarthritis happens when the cartilage cushioning your joints breaks down faster than your body can repair it. Unlike the popular image of joints simply “wearing out” with age, the disease involves an active biological process where the joint’s internal chemistry shifts toward destruction. Multiple factors drive this shift, including genetics, body weight, prior injuries, and the physical demands you place on your joints over time.
How Cartilage Breaks Down
Healthy cartilage constantly rebuilds itself. Cells called chondrocytes produce the proteins that give cartilage its structure, while enzymes quietly clear away old or damaged material. In a healthy joint, these two processes stay in balance, and the total volume of cartilage holds steady.
In osteoarthritis, that balance tips. The enzymes responsible for breaking down cartilage become overactive, chewing through the structural proteins (collagen and proteoglycans) faster than chondrocytes can replace them. Your body does try to compensate. Early on, chondrocytes multiply and ramp up production of new cartilage material. But as the disease progresses, the repair effort falls behind. Cracks and roughening appear first on the cartilage surface, then work their way deeper until large patches erode entirely, leaving bone exposed.
A key driver of this imbalance is a signaling molecule called interleukin-1, one of the body’s inflammatory messengers. It pushes chondrocytes and the cells lining the joint to produce more destructive enzymes while simultaneously suppressing the production of new collagen and proteoglycans. Making matters worse, some of these destructive enzymes can activate other inactive enzymes nearby, creating a feedback loop that accelerates cartilage loss once it starts.
The Role of Bone Beneath the Cartilage
Osteoarthritis isn’t only a cartilage problem. The layer of bone directly beneath the cartilage, called subchondral bone, plays a surprisingly early role. Animal studies have shown that abnormal remodeling of this bone layer can begin before visible cartilage damage appears. Under excessive or repetitive mechanical stress, bone cells in this region become overactive, releasing growth factors that trigger new blood vessel formation, nerve growth, and disorganized bone production.
This matters because the subchondral bone normally acts as a shock absorber, distributing force evenly beneath the cartilage. When its structure becomes disrupted and abnormally dense in some spots, it loses that ability. The cartilage above it then absorbs uneven loads, speeding up its deterioration. The new nerve growth into the remodeled bone is also one reason osteoarthritis becomes painful even in areas where cartilage loss isn’t yet severe.
Why Body Weight Matters More Than You’d Think
Carrying extra weight increases the mechanical load on your hips, knees, and ankles with every step. That alone raises the risk of cartilage damage. But the connection between obesity and osteoarthritis goes beyond physics. People with obesity also develop osteoarthritis in non-weight-bearing joints like the hands, which points to a chemical explanation.
Fat tissue, particularly the visceral fat stored around the organs, is an active producer of inflammatory molecules. These include signaling proteins like leptin, resistin, and visfatin, all of which promote inflammation and cartilage breakdown inside joints. Fat cells also release the same inflammatory messengers (interleukin-6, TNF-alpha) found in damaged joint tissue. Circulating levels of these molecules have been linked to cartilage loss and increased knee pain even after accounting for the mechanical stress of extra weight. In other words, excess body fat attacks joint cartilage through both force and chemistry.
Genetics and Joint Development
Your genes influence how strong and resilient your cartilage is from the start. One of the best-studied genetic links involves a gene called GDF5, which helps guide skeletal and joint development before birth. The protein it produces stimulates the creation of the two main structural components of cartilage.
A common variation in this gene reduces how much GDF5 protein your joints produce. People who carry two copies of this variant have a significantly higher frequency of knee osteoarthritis compared to the general population. Conversely, people with two copies of the protective version of the gene appear to have a lower risk. In mice, disabling the GDF5 gene entirely causes visible knee joint malformations, illustrating how central this single gene is to joint integrity. GDF5 is just one of many genetic contributors, but it highlights how osteoarthritis risk can be partly inherited rather than purely earned through wear and tear.
Joint Injuries and Post-Traumatic Osteoarthritis
A significant joint injury, such as a torn ACL, a meniscus tear, or a fracture that reaches into the joint surface, substantially raises your odds of developing osteoarthritis in that joint later. This is sometimes called post-traumatic osteoarthritis, and it accounts for a notable share of all OA cases, especially in younger adults.
The timeline is unpredictable. Some people develop symptomatic osteoarthritis within a year of a major injury. Others remain symptom-free for 10 to 20 years before the joint deteriorates enough to cause problems. The initial trauma damages cartilage cells directly and triggers an inflammatory cascade inside the joint. Even after the injury heals, the altered mechanics of a previously damaged joint can keep cartilage under uneven stress for years, gradually nudging the joint toward breakdown.
Occupational and Repetitive Stress
The physical demands of your work can shape which joints develop osteoarthritis and when. According to a review by the National Institute for Occupational Safety and Health, heavy physical workloads are the most consistent occupational risk factor across multiple joint sites. Specific activities tied to higher risk include frequent kneeling, regular stair climbing, crawling, sustained bending, exposure to whole-body vibration (common in construction and trucking), and repetitive hand or arm movements.
These activities don’t cause osteoarthritis overnight. They accumulate damage over years or decades by repeatedly loading the same joints beyond their comfortable recovery capacity. The cartilage repair process simply can’t keep pace with the rate of micro-damage, and the subchondral bone remodels in response to the chronic stress, compounding the problem.
Age, Sex, and Hormonal Factors
Age is the single strongest risk factor for osteoarthritis, though aging alone doesn’t cause it. What changes with age is the capacity for repair. Chondrocytes become less responsive, produce fewer structural proteins, and are more susceptible to inflammatory signals. The cumulative effect of decades of joint use also means that even minor imbalances between damage and repair have had time to add up.
Women develop osteoarthritis more frequently than men, and the gap widens sharply after menopause. The drop in estrogen appears to play a role, as estrogen has protective effects on cartilage and bone metabolism. Post-menopausal women are particularly prone to hand and knee osteoarthritis, suggesting that hormonal changes interact with the same inflammatory and metabolic pathways already described.
Why It’s Rarely Just One Cause
Most people who develop osteoarthritis have several of these factors overlapping. A person with a genetic predisposition who also carries extra weight and works a physically demanding job is facing a combination of reduced cartilage quality, elevated inflammatory signaling, and chronic mechanical overload. Each factor on its own might not be enough to overwhelm the joint’s repair systems, but together they tip the balance toward progressive cartilage loss. This is why osteoarthritis rates climb steeply with age: the longer multiple risk factors act on a joint, the harder it becomes for repair to keep up with damage.