Intraosseous subchondral PRP for knee osteoarthritis: what it is and who it is for

Intraosseous subchondral PRP is platelet-rich plasma delivered under image guidance into the bone beneath the knee joint surface — the tibial plateau and the femoral condyle — rather than into the joint space alone. It is used for knee osteoarthritis in people who are trying to hold on to function while the decision about joint replacement is being made, and it is almost always given together with an intra-articular injection rather than by itself. Regen.MD offers it, and discusses both sides of the evidence with the patient before doing so.

The honest summary is that this is an unsettled question that is moving. The one randomized trial that tested a single added intraosseous injection found no extra benefit over intra-articular PRP through six months, with more injection-related adverse events. A double-blind, placebo-controlled trial published in November 2025, which tested the intraosseous component inside a three-injection combination protocol, found the opposite. Neither result cancels the other, and both are reported in full below. No orthobiologic has been shown to regrow or regenerate articular cartilage; for advanced knee osteoarthritis, PRP is a bridge therapy prior to arthroplasty.

Key points

• What it is: PRP placed into subchondral bone at the tibial plateau and femoral condyle under image guidance, alongside an intra-articular injection.
• How it is used: as part of a combination or sequenced plan, not as a stand-alone injection. Every published clinical study of intraosseous PRP for knee osteoarthritis pairs it with an intra-articular injection; no randomized trial has tested it in isolation.
• The trial that found no added benefit: a randomized trial of 50 adults aged 50 to 65 with Kellgren-Lawrence grade III knee osteoarthritis at one Indian teaching hospital found that adding two intraosseous injections to a single intra-articular PRP injection produced no significant additional pain relief or functional improvement through six months, and the intraosseous arm reported more injection-associated adverse events.
• The trial that found benefit: a double-blind, multicenter randomized trial of 86 patients with grade III to IV disease in Spain, in which both arms received three intra-articular PRGF injections and only the intraosseous component differed, found significantly greater improvement in nearly all KOOS and WOMAC domains at 3, 6 and 12 months in the arm that received intraosseous PRGF rather than intraosseous saline.
• Who was studied: narrowly selected patients. The trials screened out poorly controlled diabetes and hypertension, autoimmune disease, high body mass index, daily opioid use, coexisting chronic pain, and significant cardiac, hepatic, renal or hematological disease.
• What it is not: a cartilage repair procedure. No orthobiologic has been shown to regrow or regenerate articular cartilage.
• Who it is for: a selected group, identified on imaging, symptom pattern and metabolic assessment during evaluation, not a default option and not an automatic upgrade to standard PRP.

What “intraosseous” and “subchondral” actually mean

Intra-articular PRP is placed inside the joint space. Intraosseous or subchondral PRP is placed into the bone immediately beneath the cartilage-bearing surface, which requires image guidance and a trocar to reach accurately.

The rationale is anatomical. Subchondral bone changes — increased remodeling, sclerosis, microfracture, marrow lesions, and the ingrowth of vessels and nerve fibers — are part of the disease process in knee osteoarthritis, and an injection into the joint space does not reach that tissue [10]. Whether reaching it changes patient outcomes is a separate question, and it is the question the trials below address.

What the evidence actually shows

The trial that found no added benefit from a single extra injection

A single-blind, parallel-group randomized clinical trial published in Injury in 2022 compared the two approaches head to head [1]. Fifty patients with Kellgren-Lawrence grade III knee osteoarthritis, aged between 50 and 65 years, were randomly allocated to intraosseous plus intra-articular PRP (n = 25) or intra-articular PRP alone (n = 25) at a single tertiary care teaching hospital in India. Mean age was 57.12 years in the combined arm and 57.00 years in the comparison arm.

How the injections were given

The intraosseous arm received 18 ml of PRP in total: 5 ml into the tibial plateau, 5 ml into the femoral condyle, and 8 ml intra-articular, all under fluoroscopic guidance. The comparison arm received the 8 ml intra-articular injection only. Each patient received one session, not a series, and all 50 were followed for six months [1].

What happened to pain and function in that trial

Both groups improved significantly on pain scores and on the Knee Injury and Osteoarthritis Outcome Score across pain, symptoms, activities of daily living, sport and recreation function, and quality of life. At six months the intraosseous arm showed a greater reduction in pain scores, but the difference between groups was not statistically significant (p = 0.422) [1].

On the functional subscales at six months, the only between-group difference that reached significance was sport and recreation function; pain (p = 0.514), symptoms (p = 0.148), activities of daily living (p = 0.991) and quality of life (p = 0.376) did not differ. A 2026 systematic review in Cartilage reports that the sport and recreation difference favored the intra-articular-only arm [9]. The authors’ own conclusion was direct: intraosseous PRP injections did not provide any additional benefit over intra-articular PRP injection until six months, in either pain relief or functional improvement [1].

What happened to tolerability in that trial

The trade-off went the other way. Patients in the intraosseous arm reported significant injection-associated adverse events and consumed a greater number of acetaminophen doses than the intra-articular-only arm [1]. The registered protocol specifies that the intraosseous injections were performed under general anesthesia [2], which is itself part of the procedural burden being weighed.

That matters for a real decision. Adding two bone injections to a joint injection is a more demanding procedure, and in this trial, given once, it bought no measurable extra benefit within the study window.

The trial that isolated the intraosseous component

A prospective, double-blind, multicenter randomized controlled trial published in Journal of Clinical Medicine in November 2025 was built to answer a narrower question [4]. Eighty-six patients with Kellgren-Lawrence grade III to IV knee osteoarthritis at two public hospitals in Spain were randomized to receive either intraosseous plasma rich in growth factors or an intraosseous saline placebo. Both arms then received the same three intra-articular PRGF injections, so the only difference between them was what went into the bone.

The intraosseous infiltration was given under fluoroscopy, 3 to 4 ml into the tibial plateau and an equivalent volume into the femoral condyle, followed one to two weeks later by two further intra-articular injections of 6 to 8 ml. Eighty-three patients were analyzed. The primary outcome was the KOOS at six months [4].

Both groups improved significantly from baseline at 3, 6 and 12 months. The intraosseous PRGF arm improved significantly more than the saline arm in nearly all KOOS and WOMAC domains — pain, symptoms, function and quality of life — at all three follow-up points. The proportion of patients reaching the minimal clinically important improvement in KOOS pain was higher in the PRGF arm at every point, though that difference reached significance only at six months (p = 0.0038; p = 0.0606 at three months and p = 0.2267 at twelve). No serious adverse events occurred; 15 patients, 7 in the PRGF arm and 8 in the saline arm, reported pain and inflammation in the first 72 hours that resolved on its own [4].

Two cautions belong with that result. Three of the six authors disclose that they are the scientific director of, or scientists at, the company whose PRGF technology was used [4]. And the trial had no third arm in which nothing at all was put into the bone, so the mechanical effect of passing a trocar into subchondral bone — a core decompression effect that both arms received — cannot be separated from the biology. The authors say so themselves.

The comparative studies that came before

A randomized trial published in Clinical Rheumatology in 2018 assigned 86 patients with grade II to III knee osteoarthritis in China to intra-articular plus intraosseous PRP given twice two weeks apart, intra-articular PRP alone, or intra-articular hyaluronic acid, and reported significantly better pain and WOMAC scores in the combined group sustained through 18 months [5]. The 2026 Cartilage review judged this trial to be at overall high risk of bias, with high risk in deviations from intended interventions and in outcome measurement [9]. It is a supportive result from a weak design.

An observational study of 60 patients with severe knee osteoarthritis, published in Cartilage in 2019, matched 30 patients treated with combined intraosseous and intra-articular PRP against 30 treated intra-articularly only. The combined group improved significantly on all KOOS and WOMAC subscales at 2, 6 and 12 months; the intra-articular-only group did not improve on any score. Minimal clinically important improvement was reached by 16 of 30 versus 8 of 30 at six months (p = 0.037) and 14 versus 5 at twelve months (p = 0.013) [6]. This was not randomized, and one author discloses a relationship with the PRGF manufacturer.

The same Indian group that published the null trial also ran a three-arm randomized trial, published in Injury in 2023, in which 96 people with grade 3 knee osteoarthritis received intra-articular PRP, combined intra-articular and intraosseous PRP, or intra-articular saline. Both PRP arms beat saline on pain and KOOS at 6 and 12 weeks. The combined arm alone showed a significant reduction in the bone turnover marker NTX-I at 12 weeks (p = 0.009) and significant reductions in synovial effusion and infrapatellar bursitis on ultrasound [3]. That is a biological signal, at 12 weeks, not a durable clinical advantage.

The observational cohorts

A retrospective study of 79 patients with grade 3 to 4 knee osteoarthritis at a single Spanish clinic reported significant improvement in all KOOS domains after office-based, ultrasound-guided intraosseous and intra-articular PRGF given weekly for three sessions, at a median follow-up of 11 months, with 88% of patients achieving at least a 10-point reduction in pain score [7]. The procedure was performed with local anesthesia in an ambulatory setting, without sedation.

A real-world cohort of 86 patients treated with combined intraosseous and intra-articular PRP, published in 2025, reported a WOMAC reduction beginning two months after the treatment course and sustained to 18 months, with 55% to 67% of patients meeting the responder threshold at the various time points [8]. Kellgren-Lawrence grade did not predict response. Higher leukocyte content in the PRP correlated negatively with improvement, which is a preparation variable rather than a route-of-delivery variable.

Both of these are uncontrolled. Neither can separate treatment effect from natural fluctuation or from expectation, and follow-up data in the real-world cohort were available for only 42% of the original patients by 18 months [8].

What the reviews conclude, and where they disagree

A 2026 systematic review of subchondral knee injections covering 24 studies and 1,109 patients concluded that intraosseous injections may improve symptoms and delay arthroplasty in selected patients, that PRP appears to be a safe option, and that overall study quality was modest, with only one of five randomized trials rated at low risk of bias [9]. A 2026 comprehensive review of intraosseous PRP concluded that the approach improves pain, function and joint structure in moderate-to-severe osteoarthritis particularly when combined with intra-articular PRP, while stating that no randomized trial had isolated the intraosseous component — a gap its literature search, which closed in May 2025, could not have known was about to be filled [10].

Set against that, a 2022 systematic review with a limited meta-analysis of five studies and 112 patients found combined intra-articular and intraosseous PRP associated with significantly better WOMAC scores than intra-articular PRP alone, while VAS and KOOS results were equivocal, and concluded that the added advantage of the intraosseous route was not well established [11]. A 2023 meta-analysis of 24 PRP randomized trials in 1,344 patients found no statistically significant difference between the combined intra-articular-plus-intraosseous subgroup and the intra-articular-only subgroup on pain scores [12].

One more thing is worth knowing before you read any summary of this literature. The two 2026 reviews describe the same 2022 trial differently: one reports it as showing no between-group difference except a sport and recreation score favoring the intra-articular arm [9], the other characterizes the same author’s trials as showing greater reductions in pain and stiffness with the combined protocol [10]. When secondary sources diverge like that, the primary trial report is the thing to read.

Who these trials studied, and who they screened out

This is the part of the evidence that rarely reaches a patient, and for someone with metabolic disease or several conditions at once it is the part that decides whether any of the above applies to them.

The exclusion lists, as the studies state them

The 2025 placebo-controlled trial required patients to be aged 40 to 75 with a body mass index under 35, and excluded poorly controlled hypertension or diabetes, systemic autoimmune disease or immunosuppressive treatment, active oncological treatment or follow-up, systemic or local infection, polyarticular disease, angular deformity greater than 15 degrees or an unstable joint, anticoagulant or antiplatelet therapy that could not be paused, pregnancy, and positive serology for syphilis, hepatitis B, hepatitis C or HIV [4].

The registered protocol for the 2022 null trial excluded Kellgren-Lawrence grade IV disease, inflammatory or post-infectious knee arthritis, prior knee replacement or knee fracture, any knee injection within three months, corticosteroid use in the preceding four weeks, daily opioid use, coexisting backache or other chronic pain disorder, body mass index above 40, blood, hematological, cardiac, hepatic or renal disorders, and any comorbidity severe enough to prevent participation in the protocol, including the at-home exercise component [2]. The registration also lists a wider enrolled population than the published report describes — ages 40 to 65 and grades II to III, against the paper’s 50 to 65 and grade III only [1][2].

The 2025 real-world cohort — a study whose stated purpose was to capture a broader population than trials do — still excluded diabetes mellitus, rheumatoid arthritis, autoimmune disease, coagulopathies, active infection, active tumors, pregnancy and severe cardiovascular disease [8]. Its authors note that they also had no data on body mass index, comorbidities such as metabolic syndrome, smoking, or physical activity, any of which could modify the result.

For two of the studies cited here — the 2018 randomized trial and the 2019 observational study — the eligibility and exclusion criteria are not reported in the records that could be obtained, so no claim is made about who they screened out [5][6].

Why that matters if you have metabolic dysfunction or several conditions

Read those lists together and a pattern emerges. Insulin resistance and poorly controlled diabetes, autoimmune and inflammatory disease, obesity above a threshold, cardiac and renal disease, polypharmacy including anticoagulation, long-standing opioid use, and coexisting pain elsewhere in the body were systematically removed from the samples. Those are not incidental exclusions. They describe a large share of the people who actually present with painful, degenerating knees.

The logical consequence runs in both directions, and both directions have to be stated. A null result in a highly selected population does not establish that the treatment fails in the patients who were screened out. It also does not establish that it works in them. What it establishes is that the question has not been asked. That is the standard difference between efficacy under trial conditions and effectiveness in practice, and it is the reason a metabolic assessment is part of evaluation here rather than an afterthought to it.

The trade-off in the least selective studies

There is an uncomfortable symmetry in this literature that is worth naming plainly. The study with almost no medical exclusion criteria at all — the 2023 retrospective series, which required only that patients be over 18 with grade 3 to 4 disease and complete outcome data [7] — is also the study with the weakest design: no randomization, no control group, no blinding. The most rigorous trials are the most selective, and the most inclusive studies are the least rigorous. No study in this literature is both.

What these designs could not measure

Single-injection trials do not test combination or sequenced care

The 2022 null trial tested one thing: whether two intraosseous injections added to a single intra-articular injection improved six-month outcomes [1]. It did not test a series. It did not test intraosseous PRP sequenced with other injections over weeks, and it did not test it alongside metabolic or inflammatory treatment. The 2025 trial that found a benefit delivered the intraosseous component as the opening move of a three-injection protocol [4], and the observational cohorts that report the longest sustained improvement also used weekly or fortnightly series of three [7][8]. A trial of a single add-on injection cannot answer whether a sequenced protocol works, and no trial has yet tested intraosseous PRP together with treatment of the metabolic terrain.

Short follow-up does not measure durability

The null trial ended at six months [1]. The 2023 three-arm trial ended at 12 weeks [3]. In the 2025 placebo-controlled trial, the separation between arms was still present at 12 months but the difference in the proportion of patients reaching a clinically important pain improvement was significant only at 6 months [4]. Where longer data exist they come from uncontrolled series reporting to 18 months [8]. Nobody has published multi-year controlled data on intraosseous PRP for the knee.

Preparation, dose and guidance are not standardized

The studies above used different platelet preparations, different volumes, different numbers of sessions, different imaging, and different anesthesia. The 2022 null trial delivered 18 ml in one session under fluoroscopy and general anesthesia [1][2]; the 2025 trial delivered 3 to 4 ml per bone site under fluoroscopy with sedation and then two further joint injections [4]; the 2023 retrospective series used ultrasound guidance, 2 ml per bone site, local anesthesia only, three weekly sessions [7]. Leukocyte content also varies between preparations, and both a 2023 meta-analysis and a 2025 cohort found leukocyte-poor preparations associated with better outcomes than leukocyte-rich ones [12][8]. When protocols differ that much, conflicting trial results are what you would expect, and pooling them tells you less than reading them.

Who it is for, and who it is not for

Intraosseous and subchondral targeting is treated here as a selected option, not as an upgrade applied to everyone who is already having PRP. It is discussed when imaging and symptom pattern point specifically toward subchondral bone as a contributor, when the added procedural burden is acceptable, and when it forms part of a plan rather than a single event.

It is not the right conversation when the primary pain generator is elsewhere, when the imaging does not support the target, or when a less demanding option has not yet been tried. In those situations a different orthobiologic or a different part of the plan is the better next step; the categories are described on our orthobiologics service page.

How risk and benefit are discussed at Regen.MD

The practice position is that there remains genuine conjecture here, that the service is offered, and that the conversation covers both sides. That means naming the trial that found no added benefit and the more demanding procedure that came with it, alongside the newer placebo-controlled evidence and the combination protocols that are producing more favorable results, and then saying which of those study populations you resemble and which you do not.

Non-coverage by an insurer is a payer decision and is not evidence about whether something works; patients sign an advance beneficiary notice for non-covered services. Entry is a paid, physician-led Clinical Evaluation with Dr. Gurpreet Singh Padda, MD, MBA, MHP, which is where imaging, symptom pattern, metabolic data and prior treatment are reviewed together and a recommendation is made.

“My ethos is to treat all of my patients as I would my own family, with the goal of giving them back their quality of life.” — Dr. Gurpreet Singh Padda, MD, MBA, MHP

Beyond the injection

Knee pain is not only a mechanical problem. Metabolic and inflammatory drivers influence how a joint behaves, and they are also, as the exclusion lists above show, the exact variables the trials removed. Addressing them is part of the evaluation rather than an add-on to it.

What this is, and what it is not, for advanced knee osteoarthritis

PRP does not regrow or regenerate articular cartilage, and no orthobiologic has been shown to do so. For advanced knee osteoarthritis, PRP is a bridge therapy prior to arthroplasty, aimed at pain and function while the decision about surgery is being made. The most favorable claim the current systematic reviews will make is that intraosseous injections may improve symptoms and delay arthroplasty in selected patients [9].

That framing is the honest one. It also means a bridge has to lead somewhere. Regen.MD does provide surgery when conservative measures have been exhausted, and Dr. Padda is a surgeon; surgery follows a completed conservative pathway rather than opening it.

What to expect on timing

The controlled evidence above is reported at six and twelve months, which is a reasonable interval at which to reassess rather than a promise about your result. Benefit, where it occurs, is evaluated over months, and the plan is revisited on the basis of measured change rather than continued by default.

For context on what is used here: Regen.MD prepares platelet-rich plasma leukocyte-poor — no white cells, no red cells — activated with calcium chloride, at two to three times baseline platelet concentration with higher dosing in the six to twelve times range, targeting a measured dose above ten billion platelets per joint.

Frequently asked questions

Sources

1. Barman A, Prakash S, Sahoo J, Mukherjee S, Maiti R, Roy SS. Single intra-articular injection with or without intra-osseous injections of platelet-rich plasma in the treatment of osteoarthritis knee: A single-blind, randomized clinical trial. Injury. 2022;53(3):1247–1253. https://pubmed.ncbi.nlm.nih.gov/35033356/ (Referenced for: 50 patients with Kellgren-Lawrence grade III knee osteoarthritis aged 50 to 65 at a single tertiary care teaching hospital in India; 25 per arm; mean age 57.12 and 57.00 years; 18 ml total in the intraosseous arm comprising 5 ml tibial plateau, 5 ml femoral condyle and 8 ml intra-articular under fluoroscopic guidance, versus 8 ml intra-articular alone; six-month follow-up; significant improvement in both arms; no significant between-group difference in pain relief at six months, p = 0.422; KOOS pain p = 0.514, symptoms p = 0.148, activities of daily living p = 0.991, quality of life p = 0.376; sport and recreation function the only significant functional between-group difference; significant injection-associated adverse events and greater acetaminophen consumption in the intraosseous arm; authors’ conclusion that intraosseous PRP did not provide additional benefit until six months.)
2. Clinical Trials Registry – India, record CTRI/2019/04/018613, Role of Intra-articular and Intra-osseous injections of Platelet Rich Plasma in OA Knee, All India Institute of Medical Sciences Bhubaneswar, via the WHO International Clinical Trials Registry Platform. https://trialsearch.who.int/Trial2.aspx?TrialID=CTRI/2019/04/018613 (Referenced for: registered target sample size of 50 and two-arm design with the same injection volumes as the published trial; registered inclusion criteria of ages 40 to 65, American College of Rheumatology criteria for medial femorotibial knee osteoarthritis, Kellgren-Lawrence grade II/III, pain of at least 20 mm on a 0–100 mm visual analog scale during level walking; registered exclusion criteria of grade IV disease, hemoglobin threshold, inflammatory or post-infectious knee arthritis, prior knee replacement repair, prior knee fracture, any knee injection within three months, daily opioid use, coexisting backache or other chronic pain disorder, body mass index greater than 40, blood, hematological, cardiac, hepatic or renal disorders, oral, topical or intra-articular steroid within four weeks, pregnancy, and comorbidity severe enough to prevent participation in the protocol; intraosseous injections performed under general anesthesia.)
3. Barman A, Bandyopadhyay D, Mohakud S, Sahoo J, Maiti R, Mukherjee S, Prakash S, Roy SS, Viswanath A. Comparison of clinical outcome, cartilage turnover, and inflammatory activity following either intra-articular or a combination of intra-articular with intra-osseous platelet-rich plasma injections in osteoarthritis knee: A randomized, clinical trial. Injury. 2023;54(2):728–737. https://pubmed.ncbi.nlm.nih.gov/36414504/ (Referenced for: 96 persons with Kellgren-Lawrence grade 3 knee osteoarthritis at a tertiary care teaching hospital in India randomized to intra-articular PRP, combined intra-articular and intraosseous PRP, or intra-articular normal saline; outcomes at baseline, 6 and 12 weeks; both PRP groups improved significantly versus saline; significant reduction in NTX-I in the combined group at 12 weeks, p = 0.009; significant reductions in synovial effusion and infrapatellar bursitis in the combined group.)
4. Sánchez Santiuste M, Vaquerizo García V, Pareja Esteban JA, Prado R, Padilla S, Anitua E. Plasma Rich in Growth Factors (PRGF) Versus Saline Intraosseous Infiltrations Combined with Intra-Articular PRGF in Severe Knee Osteoarthritis: A Prospective Double-Blind Multicentric Randomized Controlled Trial with 1-Year Follow-Up. Journal of Clinical Medicine. 2025;14(22):8075. https://pmc.ncbi.nlm.nih.gov/articles/PMC12653810/ (Referenced for: prospective, double-blind, multicenter randomized trial at two public hospitals in Spain; 106 assessed, 86 randomized, 83 analyzed; Kellgren-Lawrence grade III–IV; intraosseous PRGF versus intraosseous saline, both followed by three intra-articular PRGF injections; 3 to 4 ml per bone site under fluoroscopy; KOOS at six months as primary outcome; significantly greater improvement in nearly all KOOS and WOMAC domains at 3, 6 and 12 months in the PRGF arm; minimal clinically important improvement in KOOS pain significant only at six months, p = 0.0038, versus p = 0.0606 at three months and p = 0.2267 at twelve; no serious adverse events, 15 patients with self-resolving pain and inflammation in the first 72 hours; inclusion criteria of ages 40 to 75 and body mass index under 35; full exclusion criteria list; authors’ stated limitations including the absence of a no-infiltration arm and the recommendation to study older and higher-BMI populations; conflict of interest disclosure for three authors.)
5. Su K, Bai Y, Wang J, Zhang H, Liu H, Ma S. Comparison of hyaluronic acid and PRP intra-articular injection with combined intra-articular and intraosseous PRP injections to treat patients with knee osteoarthritis. Clinical Rheumatology. 2018;37(5):1341–1350. https://pubmed.ncbi.nlm.nih.gov/29388085/ (Referenced for: 86 patients with Kellgren-Lawrence grade II–III knee osteoarthritis randomized to combined intra-articular and intraosseous PRP given twice two weeks apart, intra-articular PRP every 14 days, or five weekly intra-articular hyaluronic acid injections; assessment to 18 months; significantly superior visual analog scale and WOMAC scores in the combined group.)
6. Sánchez M, Delgado D, Pompei O, Pérez JC, Sánchez P, Garate A, Bilbao AM, Fiz N, Padilla S. Treating Severe Knee Osteoarthritis with Combination of Intra-Osseous and Intra-Articular Infiltrations of Platelet-Rich Plasma: An Observational Study. Cartilage. 2019;10(2):245–253. https://pubmed.ncbi.nlm.nih.gov/29448817/ (Referenced for: observational study of 60 patients with severe knee osteoarthritis, 30 per group, matched for sex, age, body mass index and radiographic severity, Ahlbäck grade III–IV; significant improvement in all KOOS and WOMAC subscales at 2, 6 and 12 months in the combined group and no improvement in any score in the intra-articular group; minimal clinically important improvement 16 of 30 versus 8 of 30 at six months, p = 0.037, and 14 versus 5 at twelve months, p = 0.013; conflict of interest disclosure.)
7. Ríos Luna A, Fahandezh-Saddi Díaz H, Villanueva Martínez M, Iglesias R, Prado R, Padilla S, Anitua E. Office-Based Intraosseous Infiltrations of PRGF as an Effective Treatment for Knee Osteoarthritis: A Retrospective Observational Clinical Study. Journal of Clinical Medicine. 2023;12(13):4512. https://pmc.ncbi.nlm.nih.gov/articles/PMC10342655/ (Referenced for: retrospective review of 79 patients with Kellgren-Lawrence grade 3–4 knee osteoarthritis at a single Spanish clinic; inclusion criteria of age over 18, grade 3–4 disease, treatment with office-based intraosseous and intra-articular PRGF, completed KOOS before and after, and minimum six-month follow-up, with incomplete data as the only exclusion criterion; 8 ml intra-articular plus 2 ml into each of the tibial plateau and femoral condyle, weekly for three sessions, ultrasound-guided with local anesthesia and without sedation; median follow-up 11 months, interquartile range 7–14; significant improvement in all KOOS domains, p < 0.001; 88% achieving at least a 10-point pain reduction; conflict of interest disclosure.)
8. Catalán JM, Escarrer-Garau G, Estrany-Celià MDM, Parra C, Arbona-González L, Mercader-Barceló J, Dos-Anjos S. Intraosseous and Intra-Articular Platelet-Rich Plasma for Severe Knee Osteoarthritis: A Real-World-Outcomes Initiative. Journal of Clinical Medicine. 2025;14(11):3627. https://pmc.ncbi.nlm.nih.gov/articles/PMC12155101/ (Referenced for: prospective, non-controlled, open real-world study of 86 patients at a private orthopedic clinic in Spain, enrolled August 2020 to August 2024; inclusion of patients over 18 with Kellgren-Lawrence grade 2–4, 88% grade 3 or 4; exclusion of diabetes mellitus, rheumatoid arthritis, coagulopathies, active infections, pregnancy, active tumors, autoimmune diseases and severe cardiovascular disease; three injections at 15-day intervals with the first intraosseous under fluoroscopic guidance; significant WOMAC reduction from two months sustained to 18 months; responders 55%, 60%, 63%, 67% and 58% at 2, 3, 6, 12 and 18 months; follow-up data available for 74%, 64%, 59%, 52% and 42% of patients at those points; Kellgren-Lawrence grade not affecting response; negative correlation between PRP leukocyte count and improvement; authors’ stated absence of data on body mass index, comorbidities, smoking and physical activity; conflict of interest disclosure.)
9. Abu Salem Y, Franceschi C, Conte P, Anzillotti G, D’Arrigo D, Di Matteo B, Kon E. Subchondral Knee Injections: A Comprehensive Systematic Review of Current Clinical Outcomes, Safety, and Arthroplasty Delay. Cartilage. 2026, online ahead of print, published 16 May 2026. https://pubmed.ncbi.nlm.nih.gov/42142000/ (Referenced for: 24 studies and 1,109 patients, mean age 55, mean follow-up 38 months; five randomized controlled trials, only one rated low risk of bias overall; PRP showing a favorable safety profile and lower conversion rates to arthroplasty; conclusion that intraosseous injections may improve symptoms and delay arthroplasty in selected patients; risk-of-bias rating of the 2018 trial as high and of the 2022 trial as some concerns; characterization of the 2022 trial’s sport and recreation difference as favoring the intra-articular arm, p = 0.02; the review’s stated limitation regarding the lack of standardized patient-selection criteria and its effect on generalizability.)
10. García Bordes L, Seijas Vázquez R, Álvarez Díaz P, Castelló Egea A, Cuscó Segarra X, Barastegui Fernández D, Vázquez Gómez M, Ayestaran Calero I, Vizcaíno Navarro S, Laiz Boada P, Ferré-Aniorte A, Velasco Alcalde P, García Balletbó M, Cugat Bertomeu R. Intraosseous platelet-rich plasma for osteoarthritis: a comprehensive review. EFORT Open Reviews. 2026;11(6):512–523. https://pubmed.ncbi.nlm.nih.gov/42227238/ (Referenced for: synthesis of clinical and preclinical evidence from PubMed and Scopus up to May 2025; conclusion that intraosseous PRP, particularly when combined with intra-articular PRP, improves pain, function and joint structure in moderate-to-severe osteoarthritis; the statement that no randomized controlled trial had evaluated intraosseous PRP as an isolated intervention; the subchondral bone pathophysiology rationale; the review’s characterization of the Barman trials.)
11. Patel S, Rajnish RK, Baburaj V, Kumar P, Sharma S, Kumar V. Intraosseous Infiltration of Platelet-Rich Plasma for Knee Osteoarthritis: A Systematic Review of Literature and Limited Meta-analysis. Indian Journal of Orthopaedics. 2022;56(11):1847–1857. https://pubmed.ncbi.nlm.nih.gov/36310547/ (Referenced for: five studies and 112 patients; combined intra-articular and intraosseous PRP associated with significantly better WOMAC scores than intra-articular PRP alone, with VAS and KOOS equivocal; conclusion that the added advantage over intra-articular PRP alone is not well established.)
12. Xiong Y, Gong C, Peng X, Liu X, Su X, Tao X, Li Y, Wen Y, Li W. Efficacy and safety of platelet-rich plasma injections for the treatment of osteoarthritis: a systematic review and meta-analysis of randomized controlled trials. Frontiers in Medicine. 2023;10:1204144. https://pmc.ncbi.nlm.nih.gov/articles/PMC10333515/ (Referenced for: 24 randomized controlled trials and 1,344 patients; subgroup analysis by injection site finding no statistically significant difference between the combined intra-articular plus intraosseous subgroup and the intra-articular-only subgroup on visual analog scale pain, test for subgroup differences P > 0.05; leukocyte-poor PRP more effective than leukocyte-rich PRP for pain.)