SCIENTIFIC EVIDENCE

Bibliography — Intraosseous Injections

Systematic Reviews

1. Sundaram K, Vargas-Hernández JS, Roca Sanchez T, Moreno Moreu N, Mont MA, Higuera CA, Piuzzi NS. Are Subchondral Intraosseous Injections Effective and Safe for the Treatment of Knee Osteoarthritis? A Systematic Review. The Journal of Knee Surgery. 2019;32(11):1046-1057. A systematic review of 6 studies. It documented overall improvement in pain/function, a low complication rate (2.5%), and a high rate of avoiding total knee arthroplasty at 1 year (81%). It concluded explicitly that the technique should not be used in advanced osteoarthritis, while data for early/moderate disease were judged insufficient to support a clear recommendation either way.
2. Intraosseous platelet-rich plasma for osteoarthritis: a comprehensive review. EFORT Open Reviews. 2026. This comprehensive review includes studies indexed in PubMed and Scopus up to May 2025, evaluating both preclinical and clinical evidence on the use of intraosseous platelet-rich plasma (IO-PRP) targeting the osteochondral unit. The authors conclude that IO-PRP represents a promising therapeutic strategy for the management of osteoarthritis, particularly when combined with intra-articular (IA) PRP.

Clinical Trials & RCTs

3. 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. A multicenter, double-blind RCT in 86 patients with severe knee osteoarthritis (Kellgren-Lawrence III-IV). Adding intraosseous PRGF to intra-articular therapy produced statistically significant improvements in pain, function, and quality of life versus intraosseous saline, through 1 year of follow-up.
4. 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. Very useful study: 86 patients with K-L II–III osteoarthritis, randomized into three groups: IA + IO PRP / IA PRP / IA hyaluronic acid. The IA+IO PRP group had better VAS and WOMAC outcomes, and the improvement was sustained through 18 months.
5. Barman A, Prakash S, Sahoo J, et al. Single intra-articular injection with or without intra-osseous injections of platelet-rich plasma in the treatment of osteoarthritis of the knee: A single-blind, randomized clinical trial. Injury. 2022;53(3):1247–1253. Both PRP treatment strategies resulted in significant clinical improvement. However, the authors did not demonstrate a statistically significant additional clinical benefit of combining intra-osseous (IO) PRP injections with intra-articular (IA) PRP compared with intra-articular PRP alone.
6. Barman A, Bandyopadhyay D, Mohakud S, et al. 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 of the knee: A randomized clinical trial. Injury. 2023;54(2):728–737. In this subsequent randomized clinical trial, the same research group evaluated 96 patients with Kellgren–Lawrence grade III knee osteoarthritis, randomly assigned to receive IA-PRP, combined IA + IO PRP, or saline (control). Both PRP groups demonstrated significant improvements in VAS and KOOS scores compared with the saline control. In addition, the investigators reported changes in selected biomarkers of inflammation and cartilage/bone turnover.

Systematic Reviews

1. Sundaram K, Vargas-Hernández JS, Roca Sanchez T, Moreno Moreu N, Mont MA, Higuera CA, Piuzzi NS. Are Subchondral Intraosseous Injections Effective and Safe for the Treatment of Knee Osteoarthritis? A Systematic Review. The Journal of Knee Surgery. 2019;32(11):1046-1057. A systematic review of 6 studies. It documented overall improvement in pain/function, a low complication rate (2.5%), and a high rate of avoiding total knee arthroplasty at 1 year (81%). It concluded explicitly that the technique should not be used in advanced osteoarthritis, while data for early/moderate disease were judged insufficient to support a clear recommendation either way.

2. Intraosseous platelet-rich plasma for osteoarthritis: a comprehensive review. EFORT Open Reviews. 2026. This comprehensive review includes studies indexed in PubMed and Scopus up to May 2025, evaluating both preclinical and clinical evidence on the use of intraosseous platelet-rich plasma (IO-PRP) targeting the osteochondral unit. The authors conclude that IO-PRP represents a promising therapeutic strategy for the management of osteoarthritis, particularly when combined with intra-articular (IA) PRP.

Clinical Trials & RCTs

3. 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. A multicenter, double-blind RCT in 86 patients with severe knee osteoarthritis (Kellgren-Lawrence III-IV). Adding intraosseous PRGF to intra-articular therapy produced statistically significant improvements in pain, function, and quality of life versus intraosseous saline, through 1 year of follow-up.

4. 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. Very useful study: 86 patients with K-L II–III osteoarthritis, randomized into three groups: IA + IO PRP / IA PRP / IA hyaluronic acid. The IA+IO PRP group had better VAS and WOMAC outcomes, and the improvement was sustained through 18 months.

5. Barman A, Prakash S, Sahoo J, et al. Single intra-articular injection with or without intra-osseous injections of platelet-rich plasma in the treatment of osteoarthritis of the knee: A single-blind, randomized clinical trial. Injury. 2022;53(3):1247–1253. Both PRP treatment strategies resulted in significant clinical improvement. However, the authors did not demonstrate a statistically significant additional clinical benefit of combining intra-osseous (IO) PRP injections with intra-articular (IA) PRP compared with intra-articular PRP alone.

6. Barman A, Bandyopadhyay D, Mohakud S, et al. 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 of the knee: A randomized clinical trial. Injury. 2023;54(2):728–737. In this subsequent randomized clinical trial, the same research group evaluated 96 patients with Kellgren–Lawrence grade III knee osteoarthritis, randomly assigned to receive IA-PRP, combined IA + IO PRP, or saline (control). Both PRP groups demonstrated significant improvements in VAS and KOOS scores compared with the saline control. In addition, the investigators reported changes in selected biomarkers of inflammation and cartilage/bone turnover.