How to learn what is causing the soreness

What to tell the person examining your knee

Describe an ordinary morning before you describe your worst day. Say how many steps it takes to loosen up and whether swelling follows activity. Mention catching, buckling, night soreness, or trouble getting out of a chair. Include any fall or twist, even if it seemed minor then.

Take a written list of every medicine and supplement you currently use.

A medical provider is licensed clinic staff who examines your knee and discusses care. The provider may watch you walk, bend the joint, and check the muscles around it. Your answers help the clinician focus the exam on the most likely causes. They also help show how much the soreness affects daily life.

What to ask about an X-ray

An X-ray can show joint space, bone changes, and the position of the knee. It cannot show every tendon or other soft tissue well. Arthritis on an X-ray may explain some soreness, though visible wear may not match how the knee feels. Ask the clinician to name exactly what appears on the X-ray.

Then ask which possible causes the X-ray cannot confirm or rule out.

A scan can support the exam, yet it doesn't choose care for you. How you move, your health, your goals, and earlier care still matter. If the image and your symptoms disagree, the clinician may recheck the knee or discuss another test.

What to do when the cause remains unclear

Give the knee a little time if the exam finds no urgent concern. Follow the care instructions and note any change in swelling or motion. Return sooner if the knee locks, gives way often, or becomes hot and very swollen. Get urgent care if severe joint soreness comes with a new fever.

The likely cause may become easier to identify as your symptoms change.

If the knee doesn't settle, ask what the exam supports, what it only suggests, and what remains unknown. You can also ask which next step would change your care. A useful answer ties the choice to the soreness you feel and the movement you want back.

Sources

1. The RESTORE trial - a participant-, injector- and assessor-blinded RCT of 288 adults aged 50+ with symptomatic medial knee OA (Kellgren-Lawrence 2-3) - compared three weekly intra-articular PRP injections against saline placebo, with co-primary endpoints of 12-month knee pain and medial tibial cartilage volume on MRI. PRP did not beat placebo on either. It is the single best-designed test of the specific claim that PRP changes joint structure, and it was negative.

   Bennell KL, et al. — Effect of Intra-articular Platelet-Rich Plasma vs Placebo Injection on Pain and Medial Tibial Cartilage Volume in Patients With Knee Osteoarthritis: The RESTORE Randomized Clinical Trial.. JAMA, 2021. DOI: 10.1001/jama.2021.19415.

2. A four-arm, multicentre, single-blind phase 2/3 randomized trial of 480 knee OA patients (KL II-IV) compared autologous bone marrow aspirate concentrate, autologous adipose stromal vascular fraction and allogeneic umbilical-cord-tissue mesenchymal stromal cells against a corticosteroid injection control. At 12 months NONE of the three orthobiologic injections was superior to another, or to the corticosteroid control, and none of the four groups showed a significant change in MRI osteoarthritis score from baseline. No procedure-related serious adverse events occurred.

   Mautner K, et al. — Cell-based versus corticosteroid injections for knee pain in osteoarthritis: a randomized phase 3 trial.. Nature medicine, 2023. DOI: 10.1038/s41591-023-02632-w.

3. A 2026 systematic review and meta-analysis of 28 randomized trials of intra-articular mesenchymal stem cell-based therapies in knee OA found significant improvements in several pain and function measures (delta-VAS MD -1.67; KOOS pain MD 15.37) but NO significant difference in WOMAC, KOOS quality of life or the Lequesne index, and MRI-based WORMS scores were non-significant - indicating no consistent structural benefit. Its own conclusion: these therapies serve a primarily SYMPTOM-modifying rather than STRUCTURE-modifying role, with higher frequencies of local reactions to weigh against the symptomatic benefit.

   Awad G, et al. — Efficacy and safety of intra-articular mesenchymal stem cell-based therapies in knee osteoarthritis: A systematic review and meta-analysis of randomized controlled trials.. Clinical rheumatology, 2026. DOI: 10.1007/s10067-026-08042-w.

4. FORWARD, the longest disease-modifying osteoarthritis drug trial reported to date, gave intra-articular sprifermin (a recombinant FGF-18) or placebo to knee OA patients and followed 378 of them for 5 years. Sprifermin produced a significant, sustained dose-response INCREASE in total femorotibial cartilage thickness versus placebo - and WOMAC pain improved about 50% from baseline in ALL groups, including placebo. It is the cleanest demonstration in the literature that adding measurable cartilage and relieving pain are two different results, and that one does not deliver the other.

   Eckstein F, et al. — Long-term structural and symptomatic effects of intra-articular sprifermin in patients with knee osteoarthritis: 5-year results from the FORWARD study.. Annals of the rheumatic diseases, 2021. DOI: 10.1136/annrheumdis-2020-219181.

5. A GRADE-rated systematic review and meta-analysis of 16 randomized trials (807 participants) found that MSC therapy for chronic knee OA pain PROBABLY RESULTS IN LITTLE TO NO DIFFERENCE in pain relief at 3-6 months (WMD -0.74 cm on a 10 cm VAS against a minimally important difference of 1.5 cm) or physical functioning (WMD 2.23 on the SF-36 100-point subscale against a 10-point MID), both moderate certainty; at 12 months pain was again probably little-to-no-different (WMD -0.73 cm). The measured effect is real but sits BELOW the threshold at which a patient would notice it.

   Sadeghirad B, et al. — Mesenchymal stem cells for chronic knee pain secondary to osteoarthritis: A systematic review and meta-analysis of randomized trials.. Osteoarthritis and cartilage, 2024. DOI: 10.1016/j.joca.2024.04.021.