New Insights from the IMI-APPROACH Cohort: a dozen of papers BETWEEN 2022 and NOW TELL AN INTRIGUING STORY

APPROACH (Applied Public-Private Research enabling OsteoArthritis Clinical Headway) was a European Innovative Medicines Initiative (IMI) project designed to improve stratification and prediction of progression in knee osteoarthritis (OA).

By integrating imaging, clinical parameters, biochemical markers and machine learning in 300 participants followed over 2 years, the APPROACH consortium established one of the most deeply phenotyped OA cohorts to date — providing a foundation for smarter, more targeted clinical trials.

As a subcontractor to the University of Utrecht, Chondrometrics GmbH is proud to have contributed important longitudinal imaging biomarkers that could potentially serve as surrogate endpoints in RCTs, namely cartilage thickness and cartilage transverse relaxation time, T2.

However, the company did not only contribute quantitative imaging data through its regulatory compliant pipeline, it also very actively participated in the intellectual exploration and exploitation of the overall findings. CEO Wolfgang Wirth was particularly active as a lead  author, being involved in a dozen publications since 2022;  in one of which he was first, and in five he was senior author. (see publication list at the bottom)

Over the past four years (2022–2025), IMI-APPROACH cohort has generated a series of important publications that, taken together, tell a story, and significantly advance our understanding of structural progression and patient phenotyping in OA. More and more, knee OA is recognized as a non-uniform disease, driven by complex structural, biological and biomechanical factors.

APPROACH-related studies demonstrate the strength of quantitative MRI for detecting change in cartilage thickness and composition with high precision and longitudinal robustness. Analyses comparing radiographic joint space width with MRI-based cartilage thickness highlight the added sensitivity of quantitative MRI. Machine-learning models predicted 2-year structural progression and further showed that data-driven enrichment is feasible in interventional OA trials. Together, these findings reinforce a key message: Precision measurement is essential for efficient disease-modifying OA trials.

APPROACH research also emphasizes that OA progression is a multi-tissue process. Recent work explored fluctuations in bone marrow lesions and inflammatory MRI markers and found a link to longer-term cartilage loss. Other publications described the impact of patellofemoral damage on femorotibial cartilage loss, and the association between alignment, cartilage quality and structural adaptation

In parallel, studies investigated how structural phenotypes relate to pain outcomes and gait patterns, highlighted the complexity of structure–symptom relationships in OA

The collective evidence from APPROACH consistently shows:OA progression is heterogeneous. Imaging sensitivity matters. Stratification is key.

From the most recent ones in December 2025, to the first one in 2022, you can find all APPROACH publications with Chondrometrics involvement below:

• Jansen MP, Mastbergen SC, Wirth W, Roemer FW, Bacardit J, Bay-Jensen AC, Kloppenburg M, Blanco FJ, Haugen IK, Berenbaum F, Eijkelkamp N, Jarraya M.
  How are patient-reported pain outcomes associated with biomarker and structural pathology subtypes in knee osteoarthritis? An explorative evaluation in the IMI-APPROACH cohort.
  Osteoarthr Cartil Open. 2025 Dec 11;8(1):100726 https://pubmed.ncbi.nlm.nih.gov/41531867/
  
  
• Bax EA, Kerkhof JAJ, van Egmond N, Kuiper RJA, Rayegan H, Kloppenburg M, Blanco FJ, Haugen IK, Berenbaum F, Mastbergen SC, Eckstein F, Wirth W, Roemer FW, Kruyt MC, Weinans H, Custers R.
  The Impact of varus and valgus alignment on knee cartilage quality assessed by magnetic resonance imaging: insights from the IMI-APPROACH cohort.
  Knee. 2025 Dec;57:477-487 https://pubmed.ncbi.nlm.nih.gov/41138538/
  
  
• Salzlechner C, Wirth W, Mastbergen SC, Kloppenburg M, Blanco FJ, Haugen IK, Berenbaum F, Jansen MP.
  Does spontaneous cartilage thickening occur in osteoarthritic knees? Data from IMI-APPROACH and the OAI.
  Osteoarthritis Cartilage. 2025 Dec 6:S1063-4584 https://pubmed.ncbi.nlm.nih.gov/41360179/
  
  
• Roemer FW, Jansen M, Maschek S, Mastbergen S, Wisser A, Weinans HH, Blanco FJ, Berenbaum F, Kloppenburg M, Haugen IK, Hunter DJ, Guermazi A, Wirth W.
  Do rates of femorotibial cartilage loss in Kellgren-Lawrence 2 and 3 knees differ between those with mild-moderate vs. severe patellofemoral structural damage? – Data from the FNIH and IMI-APPROACH cohorts.
  Osteoarthritis Cartilage. 2025 Oct 12:S1063-4584 https://pubmed.ncbi.nlm.nih.gov/41086901/
  
  
• Jansen MP, Turmezei TD, Dattani K, Kessler DA, Mastbergen SC, Kloppenburg M, Blanco FJ, Haugen IK, Berenbaum F, Wirth W, Eckstein F, Roemer FW, MacKay JW.
  Cartilage thickness distribution and its dependence on demographic, radiographic, and MRI structural pathology in knee osteoarthritis-data from the IMI-APPROACH cohort.
  Skeletal Radiol. 2025 Oct;54(10):2025-2034. https://pubmed.ncbi.nlm.nih.gov/40113602/‘
  
  
• Roemer FW, Jansen MP, Maschek S, Mastbergen SC, Marijnissen AK, Wisser A, Heiss R, Weinans HH, Blanco F, Berenbaum F, Kloppenburg M, Haugen I, Eckstein F, Hunter D, Guermazi A, Wirth W.
  Fluctuation of Bone Marrow Lesions and Inflammatory MRI Markers over 2 Years and Concurrent Associations with Quantitative Cartilage Loss.
  Cartilage. 2025 Sep;16(3):308-321. https://pubmed.ncbi.nlm.nih.gov/39460605/
  
  
• Jansen MP, Hodgins D, Mastbergen SC, Kloppenburg M, Blanco FJ, Haugen IK, Berenbaum F, Eckstein F, Roemer FW, Wirth W.
  Can gait patterns be explained by joint structure in people with and without radiographic knee osteoarthritis? Data from the IMI-APPROACH cohort.
  Skeletal Radiol. 2024 Nov;53(11):2409-2416. https://pubmed.ncbi.nlm.nih.gov/38536417/
  
  
• Jansen MP, Wirth W, Bacardit J, van Helvoort EM, Marijnissen ACA, Kloppenburg M, Blanco FJ, Haugen IK, Berenbaum F, Ladel C, Loef M, Lafeber FPJG, Welsing PM, Mastbergen SC, Roemer FW.
  Machine-learning predicted and actual 2-year structural progression in the IMI-APPROACH cohort.
  QIMS. 2023 May 1;13:3298-3306 https://pubmed.ncbi.nlm.nih.gov/37179936/
  
  
• Heiss R, Laredo JD, Wirth W, Jansen MP, Marijnissen ACA, Lafeber F, Lalande A, Weinans HH, Blanco FJ, Berenbaum F, Kloppenburg M, Haugen IK, Engelke K, Roemer FW.
  Quantitative CT of the knee in the IMI-APPROACH osteoarthritis cohort: Association of bone mineral density with radiographic disease severity, meniscal coverage and meniscal extrusion.
  Bone 2023 Mar;168:116673 https://pubmed.ncbi.nlm.nih.gov/36623756/
  
  
• Jansen MP, Roemer FW, Marijnissen AKCA, Kloppenburg M, Blanco FJ, Haugen IK, Berenbaum F, Lafeber FPJG, Welsing PMJ, Mastbergen SC, Wirth W.
  Exploring the differences between radiographic joint space width and MRI cartilage thickness changes using data from the IMI-APPROACH cohort
  Skeletal Radiol. 2023 Jul;52(7):1339-1348. https://pubmed.ncbi.nlm.nih.gov/36607356/
  
  
• Wirth W, Maschek S, Marijnissen ACA, Lalande A, Blanco FJ, Berenbaum F, van de Stadt LA, Kloppenburg M, Haugen IK, Ladel CH, Bacardit J, Wisser A, Eckstein F, Roemer FW, Lafeber FPJG, Weinans HH, Jansen M.
  Test-retest precision and longitudinal cartilage thickness loss in the IMI-APPROACH cohort.
  Osteoarthritis Cartilage. 2023 Feb;31(2):238-248. https://pubmed.ncbi.nlm.nih.gov/36336198/
  
  
• Roemer FW, Jansen M, Marijnissen ACA, Guermazi A, Heiss R, Maschek S, Lalande A, Blanco FJ, Berenbaum F, van de Stadt LA, Kloppenburg M, Haugen IK, Ladel CH, Bacardit J, Wisser A, Eckstein F, Lafeber FPJG, Weinans HH, Wirth W.
  Structural tissue damage and 24-month progression of semi-quantitative MRI biomarkers of knee osteoarthritis in the IMI-APPROACH cohort.
  BMC Musculoskelet Disord. 2022 Nov 17;23(1):988 https://pubmed.ncbi.nlm.nih.gov/36397054/