Arthritis isn’t a single disease with a single cause. It’s a broad term covering more than 100 conditions that affect the joints, and each type has its own distinct trigger. Some result from physical wear on cartilage, others from an immune system gone haywire, and still others from metabolic problems or infections. About 21.3% of U.S. adults have been diagnosed with some form of arthritis, making it one of the most common chronic conditions in the country.
Understanding the specific cause behind each type matters because it changes what you can do about it. Here’s what drives the most common forms.
Osteoarthritis: Cartilage Wearing Down
Osteoarthritis is the most common type, and its root cause is the breakdown of cartilage, the slippery tissue that cushions the ends of bones where they meet at a joint. This breakdown happens in three stages. First, enzymes in the joint begin dissolving the proteins that give cartilage its structure. Second, the cartilage surface starts to crack and erode, releasing tiny fragments into the fluid surrounding the joint. Third, the joint lining absorbs those fragments and responds with inflammation, which accelerates further damage.
Once collagen in the cartilage is destroyed, it doesn’t rebuild. The body tries to compensate by thickening the bone underneath and growing bone spurs (osteophytes) along the joint edges, but these changes only add to stiffness and pain. The process is gradual, often unfolding over years or decades.
Several factors speed this process along. Age is the biggest one, simply because joints accumulate more wear over time. Obesity plays a major role too: every pound of body weight places four to six pounds of pressure on each knee joint, according to the American Academy of Orthopaedic Surgeons. That means gaining just 10 pounds adds 40 to 60 pounds of force with every step. Joint injuries also set the stage. Between 20% and 50% of people who experience a significant joint injury eventually develop arthritis in that joint, sometimes within a year but often 10 to 20 years later.
Why Women Are at Higher Risk
Osteoarthritis is significantly more common in women than men, and the gap widens sharply after menopause. Radiographic evidence of osteoarthritis is three times more common among women aged 45 to 64 compared to men the same age. Symptomatic knee osteoarthritis affects about 14% of women versus 5.8% of men; for the hands, it’s 9.5% versus 2.3%.
The connection appears to be hormonal. Estrogen receptors are found throughout joint tissues, and estrogen has a protective, anti-inflammatory effect on cartilage. When estrogen levels drop suddenly at menopause, inflammation increases and cartilage loses some of its built-in maintenance system. Studies in mice confirm this: removing estrogen receptors leads directly to cartilage damage and bone spur formation. Women also tend to experience more pain than men at the same level of joint damage, suggesting hormones influence not just the disease process but how it feels.
Rheumatoid Arthritis: The Immune System Attacks
Rheumatoid arthritis has a fundamentally different cause. Instead of cartilage wearing down from physical stress, the immune system mistakenly targets the lining of the joints (called the synovium), triggering chronic inflammation that can eventually erode bone and deform joints.
Genetics play a significant role. Specific variations of a gene called HLA-DRB1 are the strongest known genetic risk factor. These gene variants change the shape of an immune protein so that it’s more likely to bind to the body’s own tissues instead of foreign invaders like bacteria and viruses. The result is an immune response directed inward. But genetics alone don’t seal your fate. Environmental factors, particularly smoking, are strongly linked to triggering the disease in people who carry these genetic variants.
The Gut Microbiome Connection
Researchers at Mayo Clinic have found that the population of bacteria living in your gut is linked to rheumatoid arthritis outcomes. The gut microbiome helps regulate the immune system, and differences in its composition appear to predict which patients improve and which don’t. People with certain microbiome profiles at the time of diagnosis had measurably different disease trajectories. This doesn’t mean gut bacteria directly cause rheumatoid arthritis, but they likely influence how aggressively the immune system misfires and whether the disease progresses or stabilizes.
Gout: A Metabolic Problem
Gout is caused by a buildup of uric acid in the blood, a condition called hyperuricemia. Uric acid is a normal waste product created when your body breaks down purines, compounds found in many foods (especially red meat, organ meats, and certain seafood) and produced naturally by your cells. About two-thirds of the uric acid in your body comes from internal processes, not diet.
Normally, uric acid dissolves in the blood, passes through the kidneys, and leaves the body in urine. Problems arise when the body produces too much or the kidneys excrete too little. Uric acid becomes saturated in the blood at around 6.8 mg/dL, and above 7 mg/dL it can form needle-shaped crystals that deposit in joints. These crystals trigger a specific immune receptor that launches a powerful inflammatory response, causing the sudden, intense pain and swelling of a gout attack. The big toe is the classic location, but gout can strike the ankles, knees, wrists, and fingers too.
Kidney function is central to the equation. Two-thirds of uric acid leaves the body through the kidneys, and anything that impairs kidney filtration, from chronic kidney disease to certain medications, can tip the balance toward crystal formation.
Psoriatic Arthritis: Skin and Joints Together
Psoriatic arthritis develops when the same immune system malfunction that causes the scaly skin patches of psoriasis also attacks the joints. The immune system produces excess skin cells and inflames joint tissue simultaneously. Up to 30% of people with psoriasis eventually develop joint symptoms, though the arthritis occasionally appears before any skin changes do.
Like rheumatoid arthritis, it’s driven by an overactive immune response, but the specific inflammatory pathways and the pattern of joint involvement differ. Psoriatic arthritis often affects joints unevenly (one knee but not the other, for example) and commonly involves the fingers, toes, and the places where tendons attach to bone.
Ankylosing Spondylitis: Spinal Inflammation
Ankylosing spondylitis primarily targets the spine and the joints connecting the spine to the pelvis. Over time, chronic inflammation triggers the growth of new bone, which can fuse vertebrae together and severely limit flexibility.
The genetic link here is unusually strong. More than 8 out of 10 people with ankylosing spondylitis carry a gene variant called HLA-B27. However, about 8% of the general population carries this same variant without ever developing the disease, so the gene creates vulnerability rather than certainty. Other genetic and environmental factors still need to align for the disease to take hold.
Infectious Arthritis: Caused by Germs
Septic arthritis is the one form caused directly by an infection. Bacteria, viruses, or fungi enter a joint, either through the bloodstream, a wound, or during surgery, and trigger rapid inflammation. Staphylococcus aureus (staph) is the most common bacterial culprit. Unlike other forms of arthritis that develop slowly, septic arthritis is a medical emergency. The infection can damage cartilage and bone within days if untreated, leading to permanent joint destruction.
People with pre-existing joint damage, weakened immune systems, or artificial joints face the highest risk. Viral infections can also cause temporary joint inflammation that typically resolves on its own as the infection clears.
Shared Risk Factors Across Types
While each type of arthritis has its own primary cause, several risk factors cut across multiple forms. Obesity increases the risk of osteoarthritis through mechanical stress and also worsens inflammatory types like rheumatoid and psoriatic arthritis because excess fat tissue produces inflammatory chemicals. Smoking raises the risk of rheumatoid arthritis specifically in people with genetic susceptibility, and it worsens outcomes across nearly every type. Age increases risk broadly, though some forms like ankylosing spondylitis tend to start in young adulthood while osteoarthritis becomes more common after 50. Family history matters for most types, with varying degrees of genetic influence ranging from modest (osteoarthritis) to strong (ankylosing spondylitis).
Previous joint injuries create lasting vulnerability. Even an injury that heals well changes the mechanics and biology of that joint permanently, raising the odds of osteoarthritis years or decades later. Occupations or sports involving repetitive joint stress contribute in a similar way, particularly for the knees, hips, and hands.