Patients walk into our office with knee pain and a folder of imaging, and the conversation almost always lands in the same place: they want to know what can be done short of a knee replacement. If you have read anything about regenerative options, you have probably come across two names that get used almost interchangeably online: platelet-rich plasma (PRP) and prolotherapy. They are not the same thing. The mechanisms differ, the preparation differs, and the way we think about using them in a knee with osteoarthritis differs.
Here is what each one actually is, how they work in the joint, and how we think about matching a protocol to a patient.
What PRP Actually Is
Platelet-rich plasma is made from your own blood. We draw a tube (usually somewhere between 15 and 60 mL depending on the system), spin it in a centrifuge, and separate out a concentrated layer of platelets suspended in plasma. The point of concentration is that platelets carry growth factors, including PDGF, TGF-beta, VEGF, and IGF-1, stored in their alpha granules. When those platelets are activated inside a joint, they release that cargo locally.
The resulting biologic is autologous, meaning it came from you, and the composition depends heavily on the preparation system. A "leukocyte-poor" PRP (low white blood cell count) tends to be favored for intra-articular knee use, while "leukocyte-rich" preparations are more often studied in tendon work. Platelet concentration above baseline is typically targeted somewhere in the range of three to seven times, though this varies by kit and by what the clinician is trying to accomplish.
The intended biological effect in an osteoarthritic knee is modulation of the local inflammatory environment, support of chondrocyte metabolism, and influence on the synovium. PRP does not regrow cartilage in any clinically meaningful way, and any clinician telling you otherwise is overselling. What it may do is quiet the joint and improve symptoms for a period of months in appropriately selected patients.
What Prolotherapy Actually Is
Prolotherapy is older and simpler in concept. The most common formulation is dextrose prolotherapy: a hyperosmolar dextrose solution (typically 12.5 to 25 percent) mixed with a local anesthetic, injected into and around the joint and its supporting ligamentous structures.
The proposed mechanism is different from PRP. By introducing a hyperosmolar solution, the injection creates a localized osmotic and inflammatory stimulus that is thought to trigger a mild healing cascade. Some of the proposed effects include modulation of nociceptive nerve endings, stimulation of local fibroblast activity at ligament and tendon insertions, and changes in joint capsule laxity. The mechanism remains less fully characterized than PRP, but dextrose prolotherapy has been studied specifically in knee osteoarthritis with reasonable signals for pain and function at six and twelve months in some trials.
Prolotherapy injections are usually given as a series. A typical course might be three to six sessions spaced three to four weeks apart, though protocols vary. There is no blood draw, no centrifuge, and no biologic processing.
The Practical Differences
When patients ask me to lay the two side by side, I usually frame it like this:
- Source material: PRP uses your own concentrated platelets. Prolotherapy uses a dextrose solution.
- Mechanism: PRP delivers growth factors and modulates the joint environment. Prolotherapy provokes a controlled local response that may influence ligament support and pain signaling.
- Preparation: PRP requires a blood draw, centrifugation, and a sterile processing workflow on the day of treatment. Prolotherapy uses pre-mixed sterile solutions.
- Treatment cadence: PRP protocols for knee OA are often a single injection or a series of two to three spaced several weeks apart. Prolotherapy is usually a longer series.
- Cost: PRP is substantially more expensive per session because of the processing and equipment. Prolotherapy is less expensive per injection but often requires more visits.
- Downtime: Both can produce a few days of post-injection soreness as the inflammatory response does its work. Patients are usually asked to avoid NSAIDs for a window before and after, since blunting inflammation defeats part of the point.
How We Think About Matching the Patient
Knee osteoarthritis is not one disease. A 45-year-old with early chondral changes and intermittent pain after tennis is a different problem from a 68-year-old with bone-on-bone changes, a varus deformity, and daily pain climbing stairs. The imaging, the exam, the activity goals, and what has already been tried all matter.
In our practice, we tend to consider PRP for patients with mild to moderate osteoarthritis (often Kellgren-Lawrence grade 1 to 3) who have failed conservative measures like physical therapy, activity modification, and reasonable trials of oral management. We look closely at the exam for mechanical issues that an injection will not fix, including meniscal symptoms that may need a surgical opinion, significant malalignment, or instability.
Prolotherapy comes into the conversation when ligamentous laxity around the knee seems to be a meaningful driver, when cost is a consideration, or when a patient wants to start with something less intensive before deciding on PRP. Some clinicians combine approaches over time. Neither treatment is appropriate for every knee, and neither is a substitute for surgery when surgery is indicated.
We also have an honest conversation about what these injections are not. They are not a guaranteed outcome. They are not a cartilage-regrowth procedure. They will not correct a bowed leg or a torn meniscus. What they may offer, in the right patient, is a meaningful reduction in pain and improvement in function for a period of months, sometimes longer, often enough to keep someone active, keep them training, and in some cases delay a conversation about surgery.
What to Expect at a Visit
A reasonable workup starts with a detailed history, a focused knee exam, and review of any recent imaging. If imaging is outdated or incomplete, we often request weight-bearing X-rays, and sometimes MRI, before committing to a protocol. The injection itself is done in office under sterile technique, frequently with ultrasound guidance to confirm placement into the joint rather than the surrounding soft tissue. Guidance matters, and I would ask any clinician whether they use it.
After the injection, expect a few days of soreness and swelling. Ice is fine. Most patients are walking normally within a day or two, with return to higher-impact activity staged over a few weeks. We generally reassess at six weeks and again at three months to decide on next steps.
These therapies are not FDA-approved and are offered pursuant to Fla. Stat. § 458.3245.
Where to Go From Here
If you are weighing options for a painful knee and want a careful, individualized assessment rather than a one-size-fits-all pitch, we are glad to help you sort through what makes sense. You can request a consultation with our team to discuss your imaging, your goals, and whether PRP, prolotherapy, or another approach fits your situation.
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