Side Effects of Knee Injections
Knee injections carry specific risks that vary by injection type, with corticosteroids causing transient hyperglycemia and potential cartilage loss, hyaluronic acid showing minimal serious adverse events, and platelet-rich plasma demonstrating higher rates of local pain and swelling reactions.
Corticosteroid Injection Side Effects
Local Complications
- Infection risk is approximately 0.6% (1 infection per 625 injections) in native knees, with higher rates in prosthetic joints 1
- Post-injection flare occurs acutely (within hours) and can mimic septic arthritis with severe pain, swelling, and inability to bear weight—this represents a crystal-induced inflammatory response to the corticosteroid crystals 2
- Skin changes including hypopigmentation and subcutaneous atrophy can occur at injection sites 3
- Cartilage damage with accelerated osteoarthritis progression and greater cartilage volume loss has been documented with repeated injections 1, 4
- Tendon rupture risk increases with repeated corticosteroid exposure, particularly with intratendinous injections 5, 3
Systemic Complications
- Transient hyperglycemia occurs in diabetic patients, with blood glucose elevations peaking during days 1-3 post-injection; no cases of hyperosmolar hyperglycemic state or ketoacidosis have been reported 1
- Adrenal suppression or insufficiency can occur with repeated injections 3
- Facial flushing is a recognized systemic effect 3
- Hypertension may be exacerbated 3
- Osteoporosis risk increases with chronic use 3
Critical Timing Considerations
- Avoid injections within 3 months of planned knee replacement surgery—infection rates increase from 0.5% to 1.0% when injections occur 0-3 months before arthroplasty 1, 4
- Limit frequency to 3-4 injections per year maximum in the same joint to minimize cartilage damage risk 1, 4
Special Population Warnings
- Diabetic patients must monitor glucose levels for 3 days post-injection, particularly those with suboptimal control 1, 4
- Prosthetic joint patients should generally avoid routine injections unless performed by orthopedic surgeons after strict infection screening 1, 4
Hyaluronic Acid Injection Side Effects
Safety Profile
- Minimal serious adverse events have been documented with hyaluronic acid injections 1
- Local reactions including pain and swelling occur in approximately 2-4% of patients 6
- Joint infection is rare and directly related to the number of injections required (multiple injection protocols carry higher theoretical infection risk) 6
- No systemic adverse effects have been reported 6
Important Caveat
The American College of Rheumatology conditionally recommends against hyaluronic acid for knee osteoarthritis because high-quality trials show effect sizes approaching zero compared to saline 1. Despite low toxicity, the lack of proven benefit beyond placebo is the primary concern, not safety issues.
Platelet-Rich Plasma (PRP) Injection Side Effects
Local Adverse Reactions
- Pain reactions are significantly higher with leukocyte-rich PRP compared to leukocyte-poor PRP (odds ratio 1.64) 7
- Swelling occurs more frequently with leukocyte-rich PRP compared to leukocyte-poor PRP (odds ratio 1.56) 7
- Local inflammatory responses are the most common adverse events, related to leukocyte concentration in the preparation 7
Critical Limitation
The American College of Rheumatology strongly recommends against PRP for knee osteoarthritis due to heterogeneity and lack of standardization in preparations, making it impossible to predict what is actually being injected 1. This recommendation prioritizes patient safety given the inability to ensure consistent product quality.
Universal Injection Risks (All Types)
- Procedural pain during injection, which can be minimized with local anesthetics 1
- Vasovagal reactions during the procedure 5
- Bleeding or hematoma formation at the injection site 5