Cartilage loss in the knees results from a combination of mechanical wear, inflammatory processes, injuries, metabolic conditions, genetics, and the natural effects of aging. In most people, several of these factors overlap and accelerate each other. Even in healthy adults with no knee problems, tibial cartilage shrinks at an average rate of about 1.2% per year, with the pace increasing with age and body weight.
How Cartilage Breaks Down at the Cellular Level
Knee cartilage is made of two key structural proteins: type II collagen, which gives it tensile strength, and aggrecan, which helps it absorb shock by holding water. When something goes wrong in the joint, your body produces enzymes that chew through these proteins faster than cartilage cells can rebuild them. The most important of these enzymes break down collagen and aggrecan directly, and their production ramps up in the presence of inflammatory signaling molecules like TNF and IL-1β.
What makes this especially damaging is that the process feeds on itself. Inflammation triggers enzyme production, those enzymes destroy cartilage, and the debris from that destruction provokes more inflammation. One enzyme in particular creates a positive feedback loop with TNF: the more of the enzyme present, the more TNF is produced, which in turn stimulates even more enzyme activity. This self-reinforcing cycle explains why cartilage loss tends to accelerate over time rather than progress at a steady rate.
Excess Body Weight and Joint Forces
Every step you take sends a force of two to three times your body weight through your knee joints. That means each extra pound you carry translates to two or three additional pounds of pressure on your knees during normal walking. During activities like stair climbing, squatting, or rising from a chair, compressive forces can reach four to six times body weight. At maximal effort, such as a powerful leg extension, forces can spike to as high as nine times body weight.
This mechanical math is a major reason why obesity is one of the strongest modifiable risk factors for cartilage loss. But the connection isn’t purely mechanical. Excess body fat also contributes through systemic inflammation, which is covered below.
Joint Injuries and Surgical History
A torn ACL or damaged meniscus dramatically increases your risk of cartilage loss, even if the injury is surgically repaired. Roughly 30% of people who tear their ACL develop osteoarthritis within 10 years, and most will show signs of it within 15 years. At the moment of an ACL tear, cartilage degeneration has already begun: studies of acute ACL injuries find severe cartilage damage in 16% to 46% of cases right at the time of injury.
Timing of treatment matters significantly. Delaying ACL reconstruction is associated with nearly double the incidence of cartilage injury compared to early surgery. The meniscus plays a critical protective role here as well. Removing part of a damaged meniscus increases the incidence of new cartilage defects, while patients who have their meniscus repaired (rather than removed) have 64% to 84% less chance of subsequent cartilage damage. This is because the meniscus acts as a shock absorber and load distributor. Without it, force concentrates on smaller areas of cartilage, wearing them down faster.
Knee Alignment
The angle of your leg bones determines how force is distributed across the knee. In a bow-legged (varus) alignment, the inner compartment of the knee bears a disproportionate share of the load during walking. This creates higher forces toward the inside of the knee during the late phase of each step, grinding down cartilage on the medial side and eventually causing the underlying bone to collapse. Knock-kneed (valgus) alignment does the same thing to the outer compartment.
Malalignment can be something you’re born with, or it can develop gradually as cartilage wears unevenly on one side, which then worsens the alignment, which then accelerates the wear. Like the inflammatory cycle at the cellular level, this mechanical cycle tends to get worse on its own once it starts.
Metabolic Syndrome and Diabetes
Cartilage loss isn’t just a mechanical problem. People with metabolic syndrome, a cluster of conditions including central obesity, high blood sugar, high cholesterol, and insulin resistance, face cartilage breakdown driven by chemistry rather than physics. Fat tissue actively secretes inflammatory compounds like leptin and visfatin that promote joint inflammation. High cholesterol leads to oxidized LDL particles that create a pro-inflammatory environment inside the joint and cause mitochondrial dysfunction in cartilage cells.
Diabetes contributes through at least three pathways. High blood sugar increases oxidative stress and triggers new blood vessel growth in the joint lining, which recruits inflammatory cells. Persistently elevated glucose also leads to the formation of advanced glycation end-products, sticky molecular compounds that damage cartilage cells and stimulate the release of more inflammatory signals. Insulin resistance itself pushes immune cells called macrophages toward a more aggressive, inflammatory state, increasing production of the same TNF that drives the enzyme feedback loop described above. These metabolic pathways explain why people with diabetes develop knee osteoarthritis at higher rates than their body weight alone would predict.
Genetic Factors
Your genes play a meaningful role in how vulnerable your cartilage is to breakdown. The most widely confirmed genetic link to knee osteoarthritis involves a variant in the GDF5 gene, which encodes a protein involved in joint formation and the maintenance of cartilage, ligaments, and tendons. Carrying the risk version of this variant (the T allele of rs143383) increases the odds of developing knee osteoarthritis by about 17%. While that’s a modest increase from a single gene, osteoarthritis is influenced by many genetic variants acting together, and studies consistently show a significant overall genetic contribution to the disease.
Age and Sex Differences
A 10.7-year study tracking healthy adults found that everyone lost cartilage volume over the study period, at an average rate of 1.2% per year. But the rate wasn’t uniform. Each additional year of age increased the annual rate of cartilage loss, with the inner (medial) side of the knee losing volume faster than the outer side. Women lost more cartilage on the lateral (outer) side of the knee with increasing age compared to men, which may partly explain the higher rates of osteoarthritis seen in women after menopause. These changes happen in the absence of any injury, obesity, or other risk factor, representing the baseline toll of aging on joint tissue.
Running and Exercise: What the Evidence Shows
A common concern is that running wears out your knees, but the data suggest the opposite for recreational runners. A cross-sectional study comparing long-term male runners with sedentary controls found that runners had thicker cartilage in multiple knee regions. Cartilage in the front of the inner thigh bone was 9.6% thicker in runners, cartilage on the outer thigh bone was 10.8% thicker, and cartilage on the inner shinbone was 12% thicker. Runners also had greater cartilage volume in several regions.
There was one important nuance: faster running pace correlated with thinner overall cartilage and changes in cartilage composition. This suggests that moderate, recreational running stimulates cartilage to adapt and strengthen, while very high-intensity running may push past the tissue’s ability to recover. The distinction matters because cartilage responds to loading the way bone and muscle do: regular, moderate stress prompts it to maintain or build itself, while too little activity (a sedentary lifestyle) or too much high-intensity stress can both lead to deterioration.
Vitamin D and Nutritional Gaps
Earlier observational studies suggested that low vitamin D levels might accelerate cartilage loss, which seemed plausible given vitamin D’s established role in bone health. But a randomized controlled trial testing this directly found no benefit. Participants who took vitamin D supplements for two years lost the same amount of cartilage as those who took a placebo, with no significant differences in cartilage thickness, bone marrow lesion size, or joint space narrowing. The trial concluded that vitamin D does not have a major effect on knee osteoarthritis progression in people whose levels are above 15 ng/mL. For those with true vitamin D deficiency, correcting the shortfall supports bone health broadly, but it won’t specifically protect knee cartilage.
How Multiple Causes Compound
In practice, cartilage loss rarely has a single cause. A person with a genetic predisposition may do fine until a knee injury in their 30s destabilizes the joint. Someone with moderate malalignment may not develop problems until weight gain in middle age tips the balance. Metabolic inflammation from diabetes compounds the mechanical stress of obesity. The inflammatory enzyme cycle amplifies damage from any initial trigger. Understanding which factors apply to your situation is what makes it possible to target the ones you can change, whether that’s body weight, activity level, metabolic health, or the timing of treatment after an injury.