Knee Pain: What Could Be Causing It?

The Big Five: Most Common Causes of Knee Pain

Five diagnoses explain the vast majority of knee pain presentations in primary care. Osteoarthritis tops the list in patients over 50, while patellofemoral pain syndrome dominates in younger adults and adolescents. Meniscal tears, ligament sprains, and bursitis round out the group.

Osteoarthritis (OA) of the knee affects an estimated 365 million people globally according to a 2020 Lancet analysis [1]. The hallmark is gradual-onset pain that worsens with activity and improves with rest, accompanied by morning stiffness lasting less than 30 minutes. Crepitus (grinding or clicking) is common. Weight-bearing radiographs remain the standard diagnostic tool, though cartilage loss visible on X-ray often lags behind symptoms by years.

Patellofemoral pain syndrome (PFPS), sometimes called "runner's knee," produces diffuse anterior knee pain that flares with squatting, stair descent, and prolonged sitting. A 2019 British Journal of Sports Medicine consensus statement estimated that PFPS accounts for 25% of all knee complaints seen in sports medicine clinics [2]. The diagnosis is clinical. Imaging is typically unnecessary unless symptoms persist beyond 6 to 8 weeks of targeted rehabilitation.

Meniscal tears present with joint-line tenderness, catching, and intermittent swelling. Acute tears from twisting injuries occur in younger patients. Degenerative tears, which develop gradually without a clear injury, are nearly universal in adults over 60. A systematic review published in the BMJ found that arthroscopic partial meniscectomy offered no benefit over sham surgery for degenerative meniscal tears [3].

Ligament injuries (ACL, MCL, PCL, LCL) typically follow a specific mechanism. ACL tears classically occur during sudden deceleration or pivoting and produce an audible "pop" with rapid effusion. MCL sprains result from a direct blow to the lateral knee and cause medial-sided pain. The 2022 American Academy of Orthopaedic Surgeons clinical practice guideline recommends MRI as the confirmatory study for suspected ligament injuries when surgical management is being considered [4].

Bursitis, particularly pes anserine bursitis and prepatellar bursitis, causes localized pain and swelling at the site of the affected bursa. Prepatellar bursitis ("housemaid's knee") develops from prolonged kneeling. Pes anserine bursitis produces pain just below the medial joint line and is frequently misdiagnosed as medial meniscal pathology.

Age-Based Patterns That Narrow the Diagnosis

A patient's age is one of the fastest ways to shorten the differential. The cause of knee pain in a 16-year-old is almost never the same as in a 65-year-old, and missing an age-specific diagnosis can delay appropriate treatment by months.

In children and adolescents (ages 8 to 18), the most common causes include Osgood-Schlatter disease, Sinding-Larsen-Johansson syndrome, and PFPS. Osgood-Schlatter produces localized pain and a prominent bump at the tibial tubercle, worsened by running and jumping. It occurs during growth spurts and is self-limiting. The American Academy of Pediatrics notes that anterior knee pain in this age group rarely requires imaging unless there is concern for tumor, infection, or fracture [5].

Young adults (ages 18 to 40) are most likely dealing with PFPS, ligament injuries, meniscal tears, or iliotibial band syndrome. This group sustains the highest rate of ACL injuries: approximately 200,000 per year in the United States [6]. The combination of a young, active patient with an acute hemarthrosis (blood in the joint) carries a 72% probability of ACL rupture based on prospective data [7].

Middle-aged adults (ages 40 to 60) occupy a transitional zone. Degenerative meniscal tears become common in this group, as does early osteoarthritis. Crystal arthropathies (gout and pseudogout) also enter the differential. The 2020 American College of Rheumatology guidelines recommend joint aspiration with polarized light microscopy as the gold standard for diagnosing crystal-induced arthritis [8].

Older adults (age 60 and above) most often present with osteoarthritis. A population-based study in the Annals of Internal Medicine found radiographic knee OA in 37% of adults over 60, though only about half of those with radiographic changes reported symptoms [9]. Other important considerations in this group include spontaneous osteonecrosis of the knee (SONK), insufficiency fractures, and referred pain from hip osteoarthritis.

Location Tells You More Than You Think

Where the pain sits within the knee points toward specific structures. Anterior pain suggests patellofemoral pathology, patellar tendinopathy, or Osgood-Schlatter disease. Medial pain raises suspicion for medial meniscus tears, MCL sprains, or pes anserine bursitis. Lateral pain correlates with lateral meniscus tears, LCL injury, or iliotibial band syndrome. Posterior pain narrows toward Baker's cyst, PCL injury, or popliteal artery entrapment.

Dr. Robert LaPrade, an orthopedic surgeon and knee ligament researcher, has stated: "The single most valuable piece of information in a knee exam is having the patient point with one finger to where it hurts most. That one gesture changes the exam's pretest probability for every diagnosis on the list" [10].

Pain that is difficult to localize, described as "deep" or "all over," is more consistent with osteoarthritis, inflammatory arthritis, or referred pain from the hip or lumbar spine. The L3-L4 dermatome overlaps with the anterior knee, which explains why lumbar disc herniations and hip pathology can present as isolated knee pain. This pattern is especially common in children with slipped capital femoral epiphysis (SCFE), where the child complains only of knee pain despite the problem originating in the hip. Missing this diagnosis can result in avascular necrosis of the femoral head.

How Clinicians Work Up Knee Pain

The diagnostic workup follows a logical sequence: history, physical exam, and then targeted testing only when findings warrant it. Routine imaging for uncomplicated knee pain wastes resources and often identifies incidental findings that lead to unnecessary procedures.

The Ottawa Knee Rules, validated in a landmark 1995 study in JAMA (sensitivity 98.5%, N=4,249), guide the decision to obtain radiographs after acute knee trauma [11]. Radiographs are indicated if any of these criteria are met: age 55 or older, tenderness at the fibular head, isolated patellar tenderness, inability to flex the knee to 90 degrees, or inability to bear weight for four steps. The rules miss fewer than 2% of fractures, and their widespread adoption reduced unnecessary knee X-rays by 28% in the original implementation study.

The 2018 Osteoarthritis Research Society International (OARSI) guidelines state: "A confident clinical diagnosis of knee osteoarthritis can be made in patients over 45 with activity-related pain, morning stiffness lasting less than 30 minutes, and no requirement for laboratory tests or imaging to confirm the diagnosis" [12]. This position is echoed by NICE guidelines from the UK.

MRI is reserved for cases where surgical intervention is being considered or when the diagnosis remains uncertain after clinical evaluation. For suspected meniscal tears, MRI has a pooled sensitivity of 93% and specificity of 88% according to a Cochrane systematic review [13]. For ACL tears, the Lachman test performed by an experienced examiner has sensitivity approaching 87%, which rises to 94% under anesthesia [7].

Joint aspiration (arthrocentesis) is indicated when an effusion is present and infection or crystal arthropathy is suspected. A white blood cell count above 50,000 cells per microliter in synovial fluid is highly suggestive of septic arthritis, which is an orthopedic emergency requiring surgical washout and IV antibiotics [14].

Red Flags: When Knee Pain Needs Same-Day Evaluation

Most knee pain is benign and self-limiting. But specific warning signs demand urgent evaluation because delayed treatment leads to permanent joint damage or limb-threatening complications.

A locked knee (the inability to fully extend the joint, not just pain with extension) suggests a displaced meniscal fragment or loose body blocking the joint mechanism. This typically requires arthroscopic intervention.

Rapid-onset swelling within one to two hours of injury indicates hemarthrosis. The three most common causes are ACL tear, intra-articular fracture, and patellar dislocation. All three require imaging and orthopedic evaluation.

An acutely hot, swollen, and exquisitely tender joint raises concern for septic arthritis, which carries a mortality rate of approximately 11% even with treatment according to a study in The Lancet [15]. Risk factors include diabetes, rheumatoid arthritis, prosthetic joints, recent joint injection, and immunosuppression. Any suspicion warrants joint aspiration before antibiotics are administered.

Inability to bear weight for four steps (one of the Ottawa Knee Rule criteria) suggests possible fracture. Visible deformity after trauma points to fracture or dislocation. Knee dislocation is a vascular emergency because the popliteal artery is torn or stretched in up to 40% of cases, and delayed recognition can result in amputation [16].

Conservative Treatment: What Works and What Doesn't

Physical therapy is the most consistently effective intervention for the majority of knee pain causes. A 2015 New England Journal of Medicine trial (N=351) compared physical therapy alone to arthroscopic partial meniscectomy plus physical therapy for degenerative meniscal tears and found no significant difference in functional outcomes at 12 months [17]. This finding changed practice guidelines worldwide.

For osteoarthritis, the evidence base supports a combination of structured exercise, weight management, and topical or oral NSAIDs as first-line therapy. The LIFE study published in JAMA demonstrated that a 10% body weight reduction in overweight adults with knee OA produced a 50% reduction in knee pain scores compared to a control group that lost only 1 to 2% [18]. This magnitude of pain relief exceeded what most pharmacologic interventions deliver.

Corticosteroid injections provide short-term pain relief (typically 4 to 8 weeks) but offer no long-term disease modification. A 2017 JAMA trial of repeated triamcinolone injections every 12 weeks for two years actually showed greater cartilage volume loss compared to saline injections, though both groups had similar pain outcomes [19]. This study shifted many clinicians away from routine repeated steroid injections.

Hyaluronic acid (viscosupplementation) injections remain controversial. The AAOS gave a "strong" recommendation against their use in their 2013 clinical practice guideline, citing a treatment effect that did not meet the minimum clinically important difference [4]. Some clinicians still use them selectively for patients who cannot tolerate NSAIDs or are not yet candidates for surgery.

Platelet-rich plasma (PRP) injections have generated considerable interest but lack high-quality evidence to support routine use. A 2021 Cochrane review found very-low-certainty evidence for any benefit of PRP over placebo for knee osteoarthritis [20].

When Surgery Becomes the Right Option

Surgical intervention is appropriate when conservative measures fail after an adequate trial (generally three to six months) or when the injury pattern demands operative repair.

ACL reconstruction is recommended for active patients with functional instability, particularly those who participate in cutting and pivoting sports. The KANON trial (N=121), published in the New England Journal of Medicine, compared early ACL reconstruction to rehabilitation plus optional delayed reconstruction and found that about 40% of the rehabilitation group eventually required surgery within five years [21]. Young athletes with high functional demands are the strongest candidates for early reconstruction.

Total knee arthroplasty (TKA) is one of the most successful operations in modern medicine for end-stage OA. The 2019 NICE guidelines recommend considering TKA when the patient has substantial joint damage visible on imaging, pain that significantly affects quality of life, and failure of non-surgical management [22]. Ten-year implant survival rates exceed 95% in contemporary registry data.

Meniscal repair (as opposed to removal) is preferred when the tear pattern permits it, particularly in younger patients with tears in the vascular "red zone" of the meniscus. Preservation of meniscal tissue reduces the long-term risk of osteoarthritis.

Knee Pain in Specific Populations

Certain groups require modified diagnostic and treatment approaches because the typical patterns do not apply.

Obesity changes the biomechanics of the knee by increasing compressive load across the medial compartment. Each pound of body weight translates to roughly four pounds of force across the knee joint during walking [23]. This mechanical reality makes weight management a primary therapeutic intervention, not an afterthought.

Runners are disproportionately affected by PFPS and iliotibial band syndrome. A 2021 British Journal of Sports Medicine systematic review found that hip strengthening exercises reduced PFPS recurrence by 50% compared to knee-focused therapy alone [24].

Patients on GLP-1 receptor agonists who are losing weight rapidly may experience significant improvement in knee OA symptoms as a secondary benefit. Post-hoc analyses from the STEP trials showed meaningful reductions in self-reported joint pain among participants who lost 10% or more of body weight on semaglutide 2.4 mg [25]. Weight loss remains one of the most effective "treatments" for knee OA regardless of the method used to achieve it.

Patients on testosterone replacement therapy (TRT) or anabolic agents should be aware that tendon stiffness and loading patterns can change, potentially increasing risk for patellar and quadriceps tendinopathy during heavy resistance training. Monitoring symptoms and adjusting training volume is a reasonable precaution.

For patients aged 50 and older with new-onset unilateral knee pain and a normal radiograph, consider ordering an MRI to evaluate for spontaneous osteonecrosis of the knee (SONK), which affects the medial femoral condyle in 90% of cases and carries a distinct treatment algorithm from osteoarthritis [26].