Why patellofemoral bone marrow lesions drive anterior knee pain

Climbing stairs, rising from a chair, or walking down a slope — for many people with anterior knee pain, these activities produce a deep, aching discomfort behind the kneecap that rest only partly relieves. One structural correlate of that pattern is the bone marrow lesion (BML): an oedema-like signal change visible on MRI beneath the joint surface, representing an inflammatory response within the trabecular bone rather than a fracture or true marrow abnormality. The term has largely replaced the older 'bone marrow oedema' in clinical literature, though both remain in use.

In patellofemoral osteoarthritis, BMLs are far from a minority finding. An MRI methodological study of 76 patients with symptomatic patellofemoral OA found that 58 of them — 76% — carried detectable lesions on at least one imaging sequence, making BMLs a common feature of this compartment rather than an incidental one.

The relationship between BML location and pain type is clinically specific. Analysis of Osteoarthritis Initiative data from 1,412 varus knees found that lateral patellofemoral BML scores were independently associated with greater weight-bearing pain on stair-climbing (B=0.14, p=0.02), with longitudinal BML changes tracking pain changes over 24 months. That said, one patellofemoral OA imaging study found no significant correlation between BML volume and pain severity in that cohort specifically — suggesting the pain-BML link is meaningful but not absolute, and likely depends on lesion location and loading context.

Prognostically, BML grade carries weight. In a retrospective cohort of 1,011 knee OA patients, patellofemoral BML grades 2 and 3 were strongly associated with 5-year incident surgery — a finding that positions BML reduction as a structurally relevant goal, not only a symptomatic one. Serial monitoring is technically feasible: PDFS, STIR, and contrast-enhanced T1-weighted fat-suppressed sequences show strong cross-sequence correlation (ρs=0.98) and excellent reliability (ICC 0.991–0.995), enabling meaningful before-and-after comparison.

How Arthrosamid works inside the knee joint

Unlike hyaluronic acid or corticosteroid injections, Arthrosamid (2.5% iPAAG — intra-articular polyacrylamide hydrogel) is not designed to wash through the joint or temporarily modify its fluid chemistry. Administered as a single 6 mL intra-articular injection, it works by becoming structurally incorporated into the joint lining.

Within 10 to 14 days of injection, iPAAG adheres to the synovial membrane and integrates into it through a low-level, macrophage-driven foreign body response. Histopathological animal data show that by day 30 in horses and day 90 in rabbits, a stable sub-synovial scaffold has formed — a durable layer traversed by connective tissue and vessels that persists for at least two years. Because the material is non-biodegradable, this structural change does not depend on repeat dosing to be maintained.

The proposed relevance to subchondral bone marrow lesions lies in the mechanical consequences of that embedding. By reinforcing the synovial lining, iPAAG may redistribute intra-articular loads and reduce the mechanical stress transmitted to subchondral bone — the compartment where BMLs originate. This is a biologically plausible hypothesis, but the pathway from synovial scaffold integration to BML regression remains mechanistically uncharacterised in human studies.

Two investigations are working to address this gap. A first-in-NHS mechanism study launched at the Robert Jones and Agnes Hunt Orthopaedic Hospital (RJAH) in 2023, funded by Contura (>£150,000), is examining the biological pathways activated after injection. A 2025 synovial fluid biomarker study separately examined tissue-level changes following iPAAG administration. Neither has yet reported findings that directly link the scaffold to BML reduction.

What the evidence on BML reduction actually shows

The direct evidence for Arthrosamid reducing patellofemoral BMLs rests on a single published study: Maulana, Cole, and Lee (2022), reported in the Journal of Arthritis (volume 11, pages 024–026). That paper documents BML reduction on MRI in advanced patellofemoral osteoarthritis following a single intra-articular iPAAG injection — the finding directly relevant to the question this article addresses.

The study is a short clinical report spanning two journal pages: it sits at the level of an early observational case series rather than a powered randomised trial. No subsequent study specifically examining patellofemoral BML reduction with Arthrosamid has been published, and the paper has not yet been independently replicated. One of its authors, Professor Paul Lee, practises within the MSK Doctors group — a fact that is standard to disclose, and that makes independent replication a natural and important next step.

What can reasonably be drawn from this? The study establishes that BML reduction is observable on MRI after iPAAG injection in this compartment. That is a meaningful and properly documented clinical observation, using an appropriate endpoint and imaging modality. What it cannot establish — by design — is the proportion of patients who respond, the magnitude of effect at the group level, or whether the finding would hold under controlled conditions.

For a patient considering this treatment, the honest picture is as follows: one published clinical report supports the possibility of patellofemoral BML reduction; the underlying mechanism is biologically plausible; and two active investigations — the 2023 RJAH mechanism study and a 2025 synovial fluid biomarker study — are building the evidence base that will either strengthen or qualify this early signal. The question is open, active, and being investigated — which is a different position from either confirmed efficacy or absence of evidence.

The broader Arthrosamid outcomes picture at 1 to 5 years

Beyond the patellofemoral BML signal, the general efficacy record for Arthrosamid in knee osteoarthritis is considerably more substantial — and it is worth understanding both what that record shows and where its limits lie.

Two independent 5-year follow-up studies have now reported sustained pain relief following a single iPAAG injection. In the RCT extension (NCT04045431, n=58 completers), WOMAC pain improved by a mean of −16.2 points at year 5 (95% CI −20.0 to −12.4; p<0.0001), with no adverse events attributed to the device across five years. A separate open-label multicentre extension (27 completers from 49 enrolled) reported a mean WOMAC pain improvement of −14.6 points at five years (95% CI −21.4 to −7.7; p=0.0002), with no serious adverse device effects. The durability of these results — from a single injection, without top-up dosing — compares favourably with corticosteroid and hyaluronic acid, both of which returned to baseline VAS scores by 12 months in a 2025 retrospective cohort of 150 patients.

A 24-month PROMs cohort of 314 knees identified older age, lower Kellgren–Lawrence grade, absence of diabetes, and bilateral OA as factors associated with achieving a meaningful clinical improvement across VAS, Oxford Knee Score, and Lysholm outcomes. This patient profile — particularly lower KL grade — has some relevance to patellofemoral OA, which often presents in a relatively younger population and at a lower overall structural grade than advanced tibiofemoral disease.

One important caveat applies to the entire large-scale dataset: the NCT04045431 RCT and its extensions recruited predominantly tibiofemoral OA patients. Patellofemoral OA outcomes are not separately reported in that trial. The robust 5-year evidence base therefore supports Arthrosamid's general effectiveness in knee OA but cannot be read as direct confirmation of efficacy specifically in the patellofemoral compartment.

Which patients with patellofemoral OA are suitable candidates

Deciding whether Arthrosamid is appropriate for patellofemoral OA requires weighing three things together: symptom pattern, structural findings on MRI, and where the patient sits in the treatment pathway.

The most plausible candidates are people with confirmed patellofemoral OA whose anterior knee pain — particularly on stairs or loaded flexion — has not responded adequately to physiotherapy, load management, and analgesics. Arthrosamid sits at the injection stage of the pathway, after conservative measures and before surgical escalation to osteotomy, patellar realignment, or patellofemoral arthroplasty (PFA) for end-stage disease.

The 24-month PROMs cohort identified lower Kellgren–Lawrence grade, absence of diabetes, and older age as predictors of meaningful improvement — a profile that aligns reasonably well with isolated patellofemoral OA, which often presents at a lower overall structural grade than advanced tibiofemoral disease. Significant tibiofemoral involvement, very high KL grade, or diabetes may reduce expected benefit; these factors need to be weighed at consultation.

Where MRI confirms patellofemoral BMLs, there is a plausible structural rationale for treatment — and BML burden may help identify patients with a specific, imageable target. AI-assisted MRI analysis, such as onMRI™, can support grading of patellofemoral BMLs and compartmental involvement, though this remains a tool to inform discussion rather than a stand-alone decision criterion.

Suitability should be assessed by a consultant with MRI review. No injection replaces an individualised clinical evaluation.

Getting assessed at Lincolnshire Knee

The appointment at Lincolnshire Knee begins with a consultant-led clinical examination and MRI review. For anterior knee pain where patellofemoral OA and BML burden are suspected, imaging is central to confirming the compartment involved and grading structural change. The Sleaford Regeneration Hub (NG34) houses an Open MRI facility that supports this kind of compartment-specific staging, including BML assessment, without the need for referral to an external imaging centre.

Lincolnshire Knee accepts patients without a GP referral and without NHS-style waiting times. Consultations are available across two sites — Sleaford NG34 and Grantham NG31.

The assessment is not limited to determining whether iPAAG is appropriate. It will also establish whether conservative injection therapy, a joint preservation procedure, or another pathway better fits the individual's presentation, structural findings, and goals. Patellofemoral OA varies considerably between patients, and no single injection approach suits every case — the clinical consultation is where those individual factors are weighed.

To book an assessment, visit lincolnshireknee.co.uk.

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