As of 7 November 2026 · Dr. A.K. Venkatachalam

Why the bone matters

Published research now supports treating the bone beneath the cartilage as a target in its own right. Bone marrow lesions change over time, raised pressure inside the bone is linked to deep pain at rest, and two controlled trials show that treatment delivered into the bone does better than the same treatment without it.

Articular cartilage has no nerves. The subchondral bone beneath it does, along with blood vessels and a marrow space that remodels throughout life. On MRI, the abnormal areas in this bone are called bone marrow lesions (BMLs); reports often call them bone marrow oedema.

This page summarises the published evidence behind the subchondral component of the PRASAD framework. Every study cited here was carried out by other investigators. Each section is tagged with the kind of evidence it rests on.

Bone marrow lesions are not fixed

Evidence: human, longitudinal cohort, MRI (natural history, no treatment)

In the Multicenter Osteoarthritis Study, 395 knees were scanned twice, about 30 months apart. Two-thirds (66%) of the lesions present at the start had changed in size, and half had shrunk or disappeared (Roemer et al., 2009).

The direction of change mattered. Lesions that grew, and new lesions, carried a much higher risk of cartilage loss in the same region of the knee.

A bone marrow lesion is therefore an active process, not a permanent scar. That is what makes it a reasonable target for treatment.

Why the bone hurts: pressure inside a rigid compartment

Evidence: human, direct pressure measurement and perfusion MRI (mechanism)

In 1975, Arnoldi and colleagues measured pressure inside the femur and tibia near the knee in 53 patients. Pressure was low in patients with neither arthritis nor rest pain, and in half of those with arthritis but no rest pain; aching rest pain went with raised intraosseous pressure (Arnoldi et al., 1975). In a later series, every patient with typical rest pain showed venous stasis and raised pressure in the marrow near the painful joint (Arnoldi et al., 1980).

The mechanism follows from the anatomy. Blood keeps entering the bone, but its drainage is obstructed. Bone cannot expand, so the pressure must rise until blood is forced out through the narrowed exits.

Modern imaging agrees. Dynamic contrast MRI in 15 osteoarthritic knees and 7 controls showed reduced venous outflow and delayed clearance in the subchondral bone, consistent with venous stasis (Aaron et al., 2018).

What the bright MRI signal shows. On fat-suppressed sequences such as STIR, normal fatty marrow goes dark, so the bright area is water. In clinical interpretation that fluid has two sources: passive (venous congestion that cannot drain) and active (leakage from inflamed capillaries). Tissue examined after knee replacement shows necrosis, fibrosis and remodelled trabeculae within these zones; free fluid is largely lost when tissue is processed (Zanetti et al., 2000). The fluid is the active process; the scarring is what it leaves behind.

What goes into the bone matters

Evidence: human, randomised, double-blind, multicentre controlled trial

Eighty-six patients with Kellgren–Lawrence grade III–IV knee osteoarthritis were randomised. Both groups received the same intraosseous procedure followed by three intra-articular injections of plasma rich in growth factors (PRGF). The only difference was what went into the bone: PRGF in one group, saline in the other (Sánchez Santiuste et al., 2025).

The intraosseous PRGF group improved significantly more in pain, function and quality of life across most time points to one year. No serious adverse events were recorded.

Because both groups had the needle in the bone and the same joint treatment, the trial isolates the biological material delivered into the bone. It did not include follow-up MRI, so it shows a clinical effect, not lesion regression.

Disclosure: one co-author, E. Anitua, developed the PRGF system.

Where it goes matters

Evidence: human, randomised within-patient trial, 13–18 years’ follow-up

Sixty patients with comparable osteoarthritis in both knees had bone marrow concentrate harvested once and divided equally. After randomisation, one knee received it into the subchondral bone of the femur and tibia; the other received it into the joint (Hernigou et al., 2021).

At two years, clinical and MRI improvement was greater on the subchondral side. At an average of 15 years:

Delivery route	Knees	Went on to knee replacement
Subchondral bone	60	12 (20%)
Joint (intra-articular)	60	42 (70%)

The same patient, the same cells and the same dose were on both sides; only the route differed. That removes metabolism, lifestyle and general health as explanations for the gap.

Treating the lesion directly

Evidence: human, retrospective series with MRI; systematic review and meta-analysis

Subchondral bone marrow concentrate. In a retrospective analysis of 62 patients with knee osteoarthritis and MRI-confirmed bone marrow lesions, bone marrow aspirate concentrate (5 mL per site) was injected into the affected subchondral bone. Repeat MRI at 3 months showed reduced lesion scores, and pain and function improved through 12 months of clinical follow-up (Ezzi et al., Journal of Orthopaedic Surgery and Research, 2026). The study had no control group, so it documents improvement after treatment rather than isolating the injection’s effect.

Subchondroplasty. A different approach fills the lesion with calcium phosphate bone substitute for mechanical support. A 2026 meta-analysis of 12 studies and 829 patients found clinically important improvement in pain and function from one month to at least two years, with 2.4% converted to knee replacement at one year (Klincke et al., 2026). The authors note short follow-up and a lack of control groups.

The two approaches work differently, one biological and one mechanical, and neither establishes the other’s mechanism. Both show the bone beneath the cartilage can be treated.

What this establishes, and what it does not

Taken together, studies by different groups, with different methods and patients, converge on one conclusion: the subchondral bone takes part in the disease and can be treated.

Established

• Bone marrow lesions change over time, and their course tracks cartilage loss (MOST).
• Raised intraosseous pressure and venous stasis accompany deep pain at rest (Arnoldi; Aaron).
• Changing what is delivered into the bone changes the clinical result, under double-blind conditions (Sánchez Santiuste).
• Changing where the same cells are delivered changes long-term replacement rates in the same patient (Hernigou).

Not yet established

• That shrinking a lesion means cartilage has regrown.
• That every lesion needs treatment, or that all lesions share one cause.
• A consistent benefit in every study: a case-matched registry comparison found no added benefit in patient-reported outcomes from adding intraosseous bone marrow concentrate and platelets to joint injection (Centeno et al., 2021). It was not randomised, and its authors noted a possible benefit in large lesions that the sample was too small to confirm.

How this informs PRASAD

PRASAD (Platelet Rich Adipose Stromal Advanced Derivative) is a treatment framework that combines selected orthobiological approaches according to the pathology in each knee. It treats the joint and the bone beneath it as distinct targets, which is what the evidence above supports.

• The joint: leukocyte-poor platelet-rich plasma and adipose-derived stromal tissue, delivered into the joint.
• The bone: bone marrow aspirate concentrate delivered into the subchondral bone, as a standing part of the framework.
• The open slot: the “Advanced” in the name is deliberately open, so the framework can take in what further evidence supports. A-Kavach™ (an autologous alpha-2-macroglobulin fraction) is its first occupant.

Treatment follows assessment: imaging, metabolic health, alignment, muscle function and the patient’s readiness for rehabilitation.

The studies on this page did not test the full PRASAD™ framework. They support its subchondral component. Outcomes in our own patients are being documented systematically, and will be reported as they mature.

References

1. Roemer FW, Guermazi A, Javaid MK, et al. Change in MRI-detected subchondral bone marrow lesions is associated with cartilage loss: the MOST Study. Ann Rheum Dis. 2009;68(9):1461–1465. doi:10.1136/ard.2008.096834
2. Arnoldi CC, Lemperg RK, Linderholm H. Intraosseous hypertension and pain in the knee. J Bone Joint Surg Br. 1975;57-B(3):360–363. doi:10.1302/0301-620X.57B3.360
3. Arnoldi CC, Djurhuus JC, Heerfordt J, Karle A. Intraosseous phlebography, intraosseous pressure measurements and 99mTc-polyphosphate scintigraphy in patients with various painful conditions in the hip and knee. Acta Orthop Scand. 1980;51:19–28. doi:10.3109/17453678008990764
4. Aaron RK, Racine JR, Voisinet A, Evangelista P, Dyke JP. Subchondral bone circulation in osteoarthritis of the human knee. Osteoarthritis Cartilage. 2018;26(7):940–944. doi:10.1016/j.joca.2018.04.003
5. Zanetti M, Bruder E, Romero J, Hodler J. Bone marrow edema pattern in osteoarthritic knees: correlation between MR imaging and histologic findings. Radiology. 2000;215(3):835–840. doi:10.1148/radiology.215.3.r00jn05835
6. Sánchez Santiuste M, Vaquerizo García V, Pareja Esteban JA, Prado R, Padilla S, Anitua E. 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. J Clin Med. 2025;14(22):8075. doi:10.3390/jcm14228075
7. Hernigou P, Bouthors C, Bastard C, et al. Subchondral bone or intra-articular injection of bone marrow concentrate mesenchymal stem cells in bilateral knee osteoarthritis: what better postpone knee arthroplasty at fifteen years? A randomized study. Int Orthop. 2021;45(2):391–399. doi:10.1007/s00264-020-04687-7
8. Ezzi SH, Ding H, Wu S, et al. Subchondral bone marrow aspirate concentrate injection improves clinical outcomes and reduces bone marrow lesions in knee osteoarthritis: 12-month retrospective analysis. J Orthop Surg Res. 2026.
9. Klincke V, Demoor B, Dehouwer F, Tampere T, et al. Subchondroplasty for bone-marrow lesions in the osteoarthritic knee improves pain and function: a systematic review and meta-analysis. The Knee. 2026. doi:10.1016/j.knee.2026.104441
10. Centeno C, Cartier C, Stemper I, et al. The treatment of bone marrow lesions associated with advanced knee osteoarthritis: comparing intraosseous and intraarticular injections with bone marrow concentrate and platelet products. Pain Physician. 2021;24(3):E279–E288. PubMed 33988949

Dr. A.K. Venkatachalam · MS (Orth), DNB (Orth), FRCS (Glasg), MCh (Orth) (Liverpool) · Tamil Nadu Medical Council Reg. No. 38088 · Madras Joint Rejuvenation Centre, Kasthuri Hospital, West Tambaram, Chennai

General health education. Individual clinical assessment is necessary before treatment decisions.