Cortisone Shot Side Effects in the Knee, and the Case for PRP

A cortisone shot in a painful knee usually works, and that is the trap. Relief arrives fast, fades, and gets repeated while the intervals quietly shrink. The cortisone shot side effects that matter most are not the sore spot after the needle but what repeated doses do to cartilage, blood sugar, bone and the adrenal glands. Chapter 15 of The Pained Brain, the video above, by Dr. Gurpreet Singh Padda, MD, MBA, MHP, and Dr. KrisJay Fucanan, MD, sets that account beside the alternative: an injection meant to rebuild rather than silence, paired with the metabolic work that gives pain less reason to return.

How long a cortisone shot actually lasts

Across 27 randomized trials in knee osteoarthritis, steroid injection eased pain in the first weeks, and the effect shrank until it was essentially zero at 26 weeks. The orthopedic surgeons’ guideline says the effect lasted only up to three months and lowered its recommendation a level over the risk of accelerating arthritis. The rheumatologists still strongly recommend the shot, and neither guideline sets a numeric limit on repeats.

Cortisone shot side effects on cartilage, blood sugar and bone

The one trial that measured cartilage directly gave 140 patients triamcinolone or saline every twelve weeks for two years. Steroid knees lost 0.21 millimeters of cartilage against 0.10 with saline, and their pain was no better. In a large cohort, each injection raised the absolute risk of a knee replacement by 9.4 percent at nine years. The opposing evidence is strong, though. When steroid was compared with hyaluronic acid, so both groups had knees bad enough to inject, the rate ratio for joint-space narrowing was 1.00. Sicker knees get injected, and part of the cohort harm belongs to the knee, not the drug. At the hip, rapidly destructive disease followed 5.4 percent of injections, with low risk after a single dose of 40 milligrams or less and higher risk after 80 or more and after repeated shots.

The rest of the body pays too. In people with type 2 diabetes, one immediate-release knee injection raised peak glucose by a median of 169.1 mg/dL over three days, and 93 percent crossed 250. An epidural dose of 40 mg suppressed the adrenal axis for 19.7 days against 8.0 days for 20 mg, with no difference in pain relief. Among older Medicare patients with sciatica, epidural steroid was associated with a fracture hazard of 1.39, and 1.54 at the spine. One Medicare contractor caps epidural steroid at four sessions per spinal region in twelve months and calls a predetermined series unreasonable.

PRP vs cortisone injection: start with the failures

Platelet-rich plasma is your own blood, spun to concentrate platelets and the growth factors they carry, then injected into a joint or tendon. A physician who quotes only its good trials is selling something, and some of these failures are trials any regenerative physician would have wanted positive. In a blinded knee trial of 288 patients given three injections of a commercial product, pain at twelve months fell 2.1 points against 1.8 for saline, a difference that could have been zero. A single Achilles injection did nothing against a sham needle. At the hip, no injection of any kind, steroid or plasma, beat saline.

Dose reconciles the failures. Across 18 placebo-controlled knee trials, products delivering at least a million platelets per microliter beat placebo on pain by about two points at three, six and twelve months, above the threshold patients notice. Low-platelet products never crossed it, and the negative 288-patient trial used a low-platelet preparation.

Longer, not larger: how the timelines cross

In a small blinded knee trial, steroid clearly won at six weeks. By six and nine months, pooled trials favor plasma, with the six-month gap worth 9.51 points on the osteoarthritis index. Tennis elbow shows the same crossing: success at one year was 73 percent with plasma against 49 percent with steroid, and plasma was still ahead at two years. The reviewers who have followed this longest put it plainly: platelets offer a longer-lasting effect, not a bigger one. The complications are those of a needle, mostly injection-site pain and swelling.

Why the spine lags behind the knee

Inside the disc, bone marrow concentrate matched a sham procedure, and a phase 3 industry trial of injected cells missed its primary endpoint. The small joints of the back do better but modestly: pooled across facet and sacroiliac trials, plasma beat steroid by 1.32 points at three months and 1.70 at six, with limited certainty, while a blinded French facet trial found no advantage. The most recent review of randomized spine trials found durable mid-term benefit for lumbar radiculopathy and facet pain, and little inside the disc.

Coverage, money and the evidence tier

Platelet-rich plasma for joints and tendons is usually not covered, and that is a statement about money. One Medicare contractor’s non-coverage rationale cites the lack of guideline endorsement and no commercial coverage, while a commercial payer cites unproven effectiveness, so the reasoning runs in a circle. Meanwhile two European societies judged plasma appropriate in 84 of 216 knee scenarios, mainly after failed conservative care in joints that are not end-stage, and the interventional pain physicians’ 2025 low back guideline graded epidural plasma at Level III. That is modest, graded evidence, which differs from none. The asymmetry itself drives behavior: the three-month drug is paid for, the slower one is paid out of pocket, so the covered option gets repeated. How fee-for-service payment shapes repeat injections follows that incentive further.

The terrain decides whether the seed grows

A regenerative injection is a seed, and the joint is a field. In 120 patients treated with plasma for Achilles or patellar tendinopathy, those with diabetes or prediabetes had 2.41 times the odds of missing a meaningful improvement, and each unit of hemoglobin A1c raised the odds of a poor result 1.16-fold. In knees, body mass index and radiographic grade predicted failure. The platelets were not the problem, since growth-factor levels did not differ by body mass. The tissue they land in was, and in one small study inflammatory signals that rise with body mass tracked weaker responses.

Terrain work is the treatment the injection makes possible. Cartilage and muscle respond to load, and in a 273-patient trial a year of exercise-based physical therapy beat a steroid injection by 22.70 points on the osteoarthritis index. In an 18-month trial, diet-based weight loss lowered knee compressive force and interleukin-6, a circulating inflammatory signal, compared with exercise alone, and diet plus exercise cut body weight 11.4 percent with the largest pain reduction. The insulin that sits under both is its own story, and where knee arthritis pain actually comes from is the place to start on the joint itself.

What to ask before the next knee injection

Pain is not something to live with because the first three shots wore off. Natural history is kinder than that phrase: followed for six years, 35 percent of people with knee pain ran a mild, stable course and 12 percent improved. Before another steroid shot, ask how many you have had and what the plan is for month six. If plasma is offered, ask the platelet concentration and whether the joint is too far gone. Ask for fasting insulin and hemoglobin A1c as numbers, and work any medication change through your physician. Then watch the intervals: in one uncontrolled series of 368 knees given plasma as needed, the gap between doses grew from 5.42 months to 9.58. Removing damaged tendon tissue covers a step that can come before biology, and pain in older adults who cannot say where it hurts comes next. Every trial here, negatives included, is in the Technical Supplement to Chapter 15, with what each shows and does not show.

Frequently asked questions

What are the side effects of a cortisone shot?

Short term, expect possible soreness at the site and, in people with diabetes, a sharp glucose rise lasting days; one trial found peak glucose rose a median of 169.1 mg/dL. With repeated doses, one two-year trial found faster cartilage thinning, adrenal suppression scales with dose, epidural steroid is associated with more fractures in older adults, and injection within three months of knee replacement raises infection odds. Why each injection tends to buy less time than the one before is explained here.

How many cortisone shots can you get in your knee?

No single number fits every knee. The rheumatology guideline sets no numeric cap, and the orthopedic guideline notes the benefit lasts up to three months. For the spine, one Medicare contractor limits epidural steroid to four sessions per region in twelve months. The better question is what each period of relief is being used for, because shrinking intervals signal that nothing is being built during them. Genicular nerve ablation is another option for arthritic knee pain.

Is PRP better than a cortisone injection?

It depends on the time point and the preparation. Steroid wins in the first six weeks. Pooled trials favor plasma at six and nine months in knee arthritis, and in tennis elbow, one-year success was 73 percent with plasma against 49 percent with steroid. High-platelet products beat placebo while low-platelet products did not, and at the hip no injection beat saline. A summary of recent PRP clinical studies is collected here.

Is PRP covered by insurance?

Usually not. Medicare contractors and many commercial plans classify platelet-rich plasma for joints and tendons as non-covered, so it is typically an out-of-pocket expense. Non-coverage is a payment decision, not a finding that the treatment fails; professional societies grade it as modest evidence with defined uses, mainly knees that are not end-stage after conservative care. Placement matters too, because plasma has to reach the structure. Why a blind needle often misses its target is covered here.

Does blood sugar affect PRP results?

It appears to. In 120 patients treated for Achilles or patellar tendinopathy, those with diabetes or prediabetes had about two and a half times the odds of missing a meaningful improvement, and higher hemoglobin A1c independently predicted a poorer result. Platelets from heavier patients carried similar growth factors, which points to the tissue rather than the injection. How weight-loss drugs affect knee joint pain is discussed here.

Sources

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Medically reviewed by Dr. Gurpreet Singh Padda, MD, MBA, MHP, board certified in anesthesiology, pain medicine, interventional pain management, addiction medicine and obesity medicine. Adapted from Chapter 15 of The Pained Brain by Dr. Padda and Dr. KrisJay Fucanan, MD. Last reviewed September 2026.

Dr. Gurpreet Singh Padda, MD, MBA, MHP