Osteoarthritis (OA) is the most common form of arthritis, affecting over 30 million adults in the United States. It is a debilitating disease characterized by the breakdown of cartilage in joints, resulting in pain, stiffness, and loss of movement. Understanding the root causes of OA is critical for developing preventative strategies and more effective treatments. This article will examine the complex interplay of factors that contribute to the onset and progression of osteoarthritis.
What is osteoarthritis?
Osteoarthritis is a degenerative joint disease that affects the cartilage, bones, and connective tissues of joints over time. Cartilage acts as a cushion between bones, allowing smooth movement in the joint. In OA, the cartilage breaks down, causing pain, inflammation, bone spurs, and loss of function in the joint. The most commonly affected joints are the knees, hips, hands, and spine. As cartilage wears away, bone rubs against bone, resulting in stiffness, swelling, and chronic pain. Risk factors for OA include older age, female sex, obesity, joint injury, and genetics. There is no cure, but treatments aim to manage pain and maintain mobility.
Genetics
Genetics play a significant role in the development of osteoarthritis. Studies show that OA has a heritability of over 50%, meaning more than half of the risk is determined by inherited genes. Certain genetic variations affect the structure and stability of joint tissues, increasing susceptibility to cartilage breakdown. For example, defects in collagen genes COL2A1, COL11A1, and COL11A2 are linked to early-onset OA. Mutations in the GDF5 gene involved in joint formation also raise OA risk. Additionally, genes regulating bone density, inflammation, and obesity confer inherited OA risk. While genes do not guarantee OA development, they indicate a biological predisposition in many patients.
Common genetic variants linked to OA risk
| Gene | Function |
| COL2A1 | Codes for type II collagen in cartilage |
| COL11A1 | Codes for type XI collagen in cartilage |
| COL11A2 | Codes for type XI collagen in cartilage |
| GDF5 | Involved in joint development |
| DOT1L | Histone modifier regulating cartilage genes |
| IL1RN | Inflammatory marker |
| MCF2L | Obesity and inflammation related |
While genetic testing for OA risk is not routine, understanding the genes involved reveals the biological pathways that lead to cartilage degeneration when dysfunctional. This knowledge aids in developing targeted OA treatments.
Aging
Advancing age is the top risk factor for osteoarthritis. The disease rarely occurs in people under 40, with exponential increases after age 50. By age 65, radiographic evidence of OA can be found in at least one joint of over 80% of people. The age-related risks accumulate over decades and include cartilage breakdown, muscle weakness, oxidative stress, and circulation changes. Breakdown of cartilage accelerates after age 50 and is thought to be linked to reduced ability to repair joint damage. Weakening muscle strength and proprioception with aging also worsen OA progression by altering biomechanics. Age-related changes interact with other risks like genetics and obesity to promote osteoarthritis.
Prevalence of osteoarthritis by age
| Age group | Prevalence of OA |
| 18-29 | 5% |
| 30-49 | 14% |
| 50-64 | 33% |
| Over 65 | 44% |
The age-related risks for OA highlight the need for early preventive strategies. Weight management, joint-strengthening exercise, and avoiding injury in early adulthood may slow progression in later decades. Future treatments may also target age-related oxidative damage and circulatory changes affecting cartilage health.
Obesity
Obesity significantly raises risks for developing osteoarthritis, especially in the knees. Over 65% of OA cases in the knees may be attributable to excess weight. Added weight stresses the joint cartilage, meniscus, and ligaments beyond their load-bearing capacity. Just a 10-lb weight gain increases knee OA risk by 20-30%, while a gain of 30 lbs nearly triples the risk. Fat tissue also secretes inflammatory chemicals that break down cartilage. Losing weight, even just 10 lbs, can dramatically improve OA symptoms by lowering inflammation and joint loads. For obese individuals, weight loss is likely the most effective OA prevention strategy.
Obesity impacts on osteoarthritis
| Effect | Explanation |
| Joint loading | Extra body weight strains cartilage and meniscus |
| Inflammation | Fat cells release proteins that cause inflammation |
| Metabolic | Obesity alters glucose and lipid metabolism |
| Hormonal | Leptin and estrogen changes affect cartilage |
Due to the strong connection, weight management through diet and exercise should be first-line treatment for obese patients with OA. Even modest weight loss of 5-10% dramatically reduces pain and disability. Future research into the metabolic and inflammatory effects of obesity on joints may reveal additional targets for slowing OA progression.
Joint injury
Joint injuries, particularly to the knee, are well-established risk factors for developing osteoarthritis later in life. ACL tears, meniscus tears, and articular cartilage lesions increase the risk of post-traumatic OA 4-5 fold compared to uninjured knees. Impact and twisting injuries damage the structural integrity of cartilage and stabilizing ligaments. Surgical repairs do not fully prevent this damage. Altered joint mechanics after injury lead to abnormal wear patterns and cartilage breakdown. Injuries in young adulthood are especially concerning, as the cumulative damage over decades can accelerate OA onset before age 50. Protecting joint health through proper strength training, neuromuscular balance, and avoiding high-risk activities may help prevent these traumatic injuries.
Types of injuries linked to osteoarthritis
| Injury | OA risk |
| ACL tear | 4-5 times higher |
| Meniscus tear | 2-3 times higher |
| Articular cartilage defect | 3-4 times higher |
| Patellofemoral dislocation | 2-3 times higher |
Joint injury prevention through neuromuscular training programs has been proposed in younger athletic populations. Such programs improve biomechanics and stabilize joints during activity. Further research is needed on cartilage regeneration after joint trauma and preventing the onset of post-traumatic OA.
Mechanical factors
Abnormal joint mechanics and misalignment are important contributors to osteoarthritis development and progression. Chronic excessive loading in one area leads to uneven cartilage wear. Varus (bow-legged) and valgus (knock-kneed) misalignments increase loads on the medial and lateral compartments of the knee respectively. Metabolic disorders like hemochromatosis that affect cartilage properties also disturb joint mechanics. Muscle weakness in the leg or back reduces stability and stresses joints. High-impact activities such as running on hard surfaces are linked to higher OA incidence in hips and knees. Understanding each patient’s alignment and movement pattern is key to provide targeted mechanical interventions.
Mechanical causes of osteoarthritis
| Factor | Effects |
| Malalignment | Overloads one side of joint |
| Muscle weakness | Reduces stability, causes imbalance |
| Joint laxity | Leads to instability, cartilage damage |
| High-impact activities | Chronic repetitive overloading |
| Metabolic disorders | Affect cartilage properties |
Treatment strategies include bracing, taping, muscle strengthening, activity modifications, shoe orthotics, and gait training. For severe misalignments, corrective osteotomies surgically realign the joint. Understanding each patient’s mechanical environment is key to develop a targeted treatment plan.
Inflammation
Chronic low-grade inflammation emerges as both a cause and consequence of osteoarthritis. The innate immune system becomes activated within OA joints, releasing inflammatory cytokines like IL-1, IL-6, and TNF-alpha. These proteins degrade cartilage, stimulate nerves, and spur degenerative changes. Anti-inflammatory drugs like NSAIDs provide temporary OA symptom relief by blocking them. Joint injury also triggers acute inflammation that fails to fully resolve, initiating cartilage breakdown. Obesity promotes systemic inflammation, contributing to OA development in multiple joints. Identifying patients with high inflammatory biomarkers may better target those who could benefit from anti-inflammatory therapies.
Effects of inflammation in osteoarthritis
| Effect | Process |
| Cartilage breakdown | Activates degradative enzymes |
| Joint pain | Sensitizes nerve endings |
| Bone changes | Promotes osteophyte formation |
| Synovitis | Thickens synovial membrane |
Future osteoarthritis treatments may target specific inflammatory pathways activated in OA patients. Diet and exercise also help resolve chronic inflammation. Protecting joints from inflammatory insults early in life may prevent the downstream impacts on cartilage health.
Conclusion
Osteoarthritis development results from a complex interplay of many biological, mechanical, and environmental factors over time. Genetics underlie biological joint vulnerabilities, while aging, obesity, injury, inflammation, and mechanical imbalances stress the joint structures beyond their inherent capacity. Identifying combinations of risks unique to each patient allows for individualized management plans. Preventing joint deterioration earlier in adulthood and resolving mechanical problems before cartilage breakdown are key OA prevention strategies. With many pathways identified, researchers continue working to translate insights on OA causes into impactful new treatments.