Research – chondrometrics

Representatives of Chondrometrics are actively involved in academic research and publish continuously and extensively in the biomedical literature. The current section provides snapshots on these activities, presenting:

Infographics Posters

Publication Indices for lead authors of Chondrometrics

The Google Scholar publication metrics of Chondrometrics authors (Date: May 15^st, 2026)

Felix Eckstein	All	Past 5 Years
Total Citations	42,373	11,661
H-Index *	112	49
i10-index **	454	293

Wolfgang Wirth	All	Past 5 Years
Total Citations	9779	4532
H-Index *	57	35
i10-index **	169	141

* for explanation of this widely accepted metric of scientific impact, please check: https://de.wikipedia.org/wiki/H-Index, https://en.wikipedia.org/wiki/H-Index
** The i10 index is a specific metric used primarily within Google Scholar, to evaluate the “breadth” of scientific impact of a specific researcher. The index counts all authored or co-authored publications that are cited >10x since publication

Chondrometrics Industry Projects & Publications

Industry-Funded Clinical Trials Completed by Chondrometrics GmbH.

Table listing Pharma-Industry-initiated clinical trials with Chondrometrics participation, specifying study phase, period, # of knees, # of time points, # of total MRIs, # of sites & location of sites

Vendor	Clin. Study Phase	Analysis Period	# of Knees	# of Time Points	# MRIs analyzed (- drop out)	# of Sites	Location of Sites
Vendor	Clin. Study Phase	Analysis Period	# of Knees	# of Time Points	# MRIs analyzed (- drop out)	# of Sites	NAM	SAM	EUR	SA	ASIA	AUS
I	Ph2A	2005-2010	192	6	approx. 1200	28	X		X		X
II	Ph2	2011	110	2-3	approx. 240	46	X
III	Ph2B	2013-2019	549	6	approx. 4000	13	X	X	X		X
IV	Ph2	2014	89	2-3	approx. 220	8	X
V	Ph2	2015-2017	190	3	approx. 550	15	X
VI	Ph2B	2018-2020	932	3	approx. 2700	81	X	X	X		X
VII	Ph2B	2022-2024	572	5	approx. 2500	76	X	X	X		X	X
VIII	Ph3	2024-2026	2 x 510	4	approx. 4000	50	X
IX	Ph3	2024-2026	321	4	approx. 600	15						X
X	Ph2	2026-2028	206	3	approx. 600	20			X

# = number; approx = approximately
NAM = North America, SAM = South AM, EUR = Europe, SA = South Africa, AUS = Australia;

Publications by Chondrometrics GmbH originating from Industry-Funded Projects

more recent projects are listed first

Eurostars – Osteoarthritis (OA) Bio – EU Project (4P Pharma)

1) Wirth W, Maschek S, Wisser A, Eder J, Baumgartner CF, Chaudhari A, Berenbaum F, Eckstein F – on behalf of the OA-BIO Consortium.

Evaluation of an automated laminar cartilage T2 relaxation time analysis method in an early osteoarthritis model.

Skeletal Radiol. 2025 Mar ; 54(3):571-584 / PMID:

2) Eckstein F, Brisson NM, Maschek S, Wisser A, Berenbaum F, Duda GN, Wirth W – on behalf of the osteoarthritis (OA)-Bio consortium

Clinical validation of fully automated laminar knee cartilage transverse relaxation time (T2) analysis in anterior cruciate ligament (ACL)-injured knees.

Quant Imaging Med Surg. 2024 Jul 1; 14(7):4319-4332 / PMID: 39022226

FORWARD (Sprifermin) Phase IIB Study (Formation Bio)

1) Eckstein F, Maschek S, Wirth W, Ladel C, Bihlet AR, Knight C, Somberg K, Zhao L

Unbiased analysis of knee cartilage thickness change over three years after sprifermin vs. placebo treatment – A post-hoc analysis from the phase 2B FORWARD study.

Osteoarthritis and Cartilage Open. 2024 ; in press / PMID:

2) Eckstein F, Wisser A, Maschek S, Wirth W, Ladel C, Bihlet AR, Knight C, Somberg K, Zhao L.

Is detection of disease-modifying osteoarthritis drug treatment more effective when performing cartilage morphometry without blinding to MR image acquisition order?

Osteoarthritis Cartilage. 2024 Jun 4; / PMID: 38844160

European Union Innovative Medicines Initiative (IMI) –APPROACH Study (Glaxo Smith Kline [GSK] & Merck KGaA)

1) Jansen MP, Wirth W, Bacardit J, van Helvoort EM, Marijnissen ACA, Kloppenburg M, Blanco FJ, Haugen IK, Berenbaum F, Ladel CH, Loef M, Lafeber FPJG, Welsing PM, Mastbergen SC, Roemer FW.

Machine-learning predicted and actual 2-year structural progression in the IMI-APPROACH cohort.

Quant Imaging Med Surg. 2023 May 1; 13(5):3298-3306 / PMID: 37179936

2) 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 / PMID: 36336198

3) 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; / PMID: 36397054

ROCELLA (S201086/GLPG1972) Phase II Study (Galapagos, Servier)

1) Schnitzer T, Pueyo M, Deckx H, van der Aar E, Bernard K, Hatch S, van der Stoep M, Grankov S, Phung D, Imbert O, Chimits D, Muller K, Hochberg MC, Bliddal H, Wirth W, Eckstein F, Conaghan PG.

Evaluation of S201086/GLPG1972, an ADAMTS-5 inhibitor, for the treatment of knee osteoarthritis in ROCCELLA: a phase 2 randomized clinical trial.

Osteoarthritis Cartilage. 2023 Jul ; 31(7):985-994 / PMID: 37059327

2) Imbert O, Deckx H, Bernard K, van der Aar E, Pueyo M, Saeed N, Fuerst T, Wirth W, Conaghan PG, Eckstein F.

The design of a randomized, placebo-controlled, dose-ranging trial to investigate the efficacy and safety of the ADAMTS-5 inhibitor S201086/GLPG1972 in knee osteoarthritis.

Osteoarthr Cartil Open. 2021 Aug 16; 3(4):100209 / PMID: 36474770

3) Imbert O, Chimits D, Guedj M, Lorieau F, Bernard K, Lalande A, Wirth W, Eckstein F, Pueyo M.

A simple inclusion criteria combination increases the rate of cartilage loss in patients with knee osteoarthritis.

Osteoarthr Cartil Open. 2021 Jun 5; 3(3):100188 / PMID: 36474822

FORWARD (Sprifermin) Phase IIB Study (Merck KGaA)

1) Eckstein F, Hochberg MC, Guehring H, Moreau F, Ona V, Bihlet AR, Byrjalsen I, Andersen JR, Daelken B, Guenther O, Ladel C, Michaelis M, Conaghan PG.

Long-term structural and symptomatic effects of intra-articular sprifermin in patients with knee osteoarthritis: 5-year results from the FORWARD study.

Ann Rheum Dis. 2021 Aug ; 80(8):1062-1069 / PMID: 33962962

2) Guehring H, Moreau F, Daelken B, Ladel C, Guenther O, Bihlet AR, Wirth W, Eckstein F, Hochberg M, Conaghan PG.

The effects of sprifermin on symptoms and structure in a subgroup at risk of progression in the FORWARD knee osteoarthritis trial.

Semin Arthritis Rheum. 2021 Apr ; 51(2):450-456 / PMID: 33752164

3) Brett A, Bowes MA, Conaghan PG, Ladel C, Guehring H, Moreau F, Eckstein F.

Automated MRI assessment confirms cartilage thickness modification in patients with knee osteoarthritis: post-hoc analysis from a phase II sprifermin study.

Osteoarthritis Cartilage. 2020 Nov ; 28(11):1432-1436 / PMID: 32860991

4) Eckstein F, Kraines JL, Aydemir A, Wirth W, Maschek S, Hochberg MC.

Intra-articular sprifermin reduces cartilage loss in addition to increasing cartilage gain independent of location in the femorotibial joint: post-hoc analysis of a randomised, placebo-controlled phase II clinical trial.

Ann Rheum Dis. 2020 Apr ; 79(4):525-528 / PMID: 32098758

5) Hochberg MC, Guermazi A, Guehring H, Aydemir A, Wax S, Fleuranceau-Morel P, Reinstrup Bihlet A, Byrjalsen I, Ragnar Andersen J, Eckstein F.

Effect of Intra- Articular Sprifermin vs Placebo on Femorotibial Joint Cartilage Thickness in Patients With Osteoarthritis: The FORWARD Randomized Clinical Trial.

JAMA. 2019 Oct 8; 322(14):1360-1370 / PMID: 31593273

Osteoarthritis Initiative (OAI) POMA, FNIH, etc. Studies (co-funding by Merck KGaA and/or Novartis)

1) Kwoh CK, Guehring H, Aydemir A, Hannon MJ, Eckstein F, Hochberg MC.

Predicting knee replacement in participants eligible for disease-modifying osteoarthritis drug treatment with structural endpoints.

Osteoarthritis Cartilage. 2020 Jun ; 28(6):782-791 / PMID: 32247871

2) Roemer FW, Kwoh CK, Fujii T, Hannon M, Boudreau RM, Hunter DJ, Eckstein F, John MR, Guermazi A.

From Early Radiographic Knee Osteoarthritis to Joint Arthroplasty: Determinants of Structural Progression and Symptoms.

Arthritis Care Res (Hoboken). 2018 Dec ; 70(12):1778-1786 / PMID: 29438603

3) Wirth W, Hunter DJ, Nevitt MC, Sharma L, Kwoh CK, Ladel C, Eckstein F.

Predictive and concurrent validity of cartilage thickness change as a marker of knee osteoarthritis progression: data from the Osteoarthritis Initiative.

Osteoarthritis Cartilage. 2017 Dec ; 25(12):2063-2071 / PMID: 28838858

4) Eckstein F, Boudreau R, Wang Z, Hannon MJ, Duryea J, Wirth W, Cotofana S, Guermazi A, Roemer F, Nevitt M, John MR, Ladel C, Sharma L, Hunter DJ, Kwoh CK; OAI Investigators.

Comparison of radiographic joint space width and magnetic resonance imaging for prediction of knee replacement: A longitudinal case-control study from the Osteoarthritis Initiative.

Eur Radiol. 2016 Jun ; 26(6):1942-51 / PMID: 26376884

5) Hitzl W, Wirth W, Maschek S, Cotofana S, Nevitt M, John MR, Ladel C, Eckstein F.

Greater Lateral Femorotibial Cartilage Loss in Osteoarthritis Initiative Participants with Incident Total Knee Arthroplasty: A Prospective Cohort Study.

Arthritis Care Res (Hoboken). 2015 Oct ; 67(10):1481-6 / PMID: 25939334

6) Roemer FW, Kwoh CK, Hannon MJ, Hunter DJ, Eckstein F, Wang Z, Boudreau RM, John MR, Nevitt MC, Guermazi A.

Can structural joint damage measured with MR imaging be used to predict knee replacement in the following year?

Radiology. 2015 Mar ; 274(3):810-20 / PMID: 25279436

7) Eckstein F, Boudreau RM, Wang Z, Hannon MJ, Wirth W, Cotofana S, Guermazi A, Roemer F, Nevitt M, John MR, Ladel C, Sharma L, Hunter DJ, Kwoh CK; OAI investigators.

Trajectory of cartilage loss within 4 years of knee replacement–a nested case-control study from the osteoarthritis initiative.

Osteoarthritis Cartilage. 2014 Oct ; 22(10):1542-9 / PMID: 24792212

8) Eckstein F, Kwoh CK, Boudreau RM, Wang Z, Hannon MJ, Cotofana S, Hudelmaier MI, Wirth W, Guermazi A, Nevitt MC, John MR, Hunter DJ; OAI investigators.

Quantitative MRI measures of cartilage predict knee replacement: a case-control study from the Osteoarthritis Initiative.

Ann Rheum Dis. 2013 May ; 72(5):707-14 / PMID: 22730370

Sprifermin Phase IIA Proof of Concept (POC) Study (Merck KGaA)

1) Roemer FW, Aydemir A, Lohmander S, Crema MD, Marra MD, Muurahainen N, Felson DT, Eckstein F, Guermazi A.

Structural effects of sprifermin in knee osteoarthritis: a post-hoc analysis on cartilage and non-cartilaginous tissue alterations in a randomized controlled trial.

BMC Musculoskelet Disord. 2016 Jul 9; 17:267 / PMID: 27393009

2) Eckstein F, Wirth W, Guermazi A, Maschek S, Aydemir A.

Intraarticular sprifermin not only increases cartilage thickness, but also reduces cartilage loss: location-independent post hoc analysis using magnetic resonance imaging.

Arthritis Rheumatol. 2015 Nov ; 67(11):2916-22 / PMID: 26138203

3) Lohmander LS, Hellot S, Dreher D, Krantz EF, Kruger DS, Guermazi A, Eckstein F.

Intraarticular sprifermin (recombinant human fibroblast growth factor 18) in knee osteoarthritis: a randomized, double-blind, placebo-controlled trial.

Arthritis Rheumatol. 2014 Jul ; 66(7):1820-31 / PMID: 24740822

Osteoarthritis Initiative (OAI) Chondrometrics-initiated Industry Consortium (Pfizer, Eli Lilly, MerckSerono, GlaxoSmithKline, OAI-CC UCSF, Wyeth, Centocor, Novartis)

1) Buck RJ, Le Graverand MH, Wirth W, Eckstein F.

Choice of knee cartilage thickness change metric for different treatment goals in efficacy studies.

Semin Arthritis Rheum. 2017 Dec ; 47(3):315-322 / PMID: 28645453

2) Cotofana S, Benichou O, Hitzl W, Wirth W, Eckstein F.

Is loss in femorotibial cartilage thickness related to severity of contra-lateral radiographic knee osteoarthritis?–longitudinal data from the Osteoarthritis Initiative.

Osteoarthritis Cartilage. 2014 Dec ; 22(12):2059-66 / PMID: 25262648

3) Maschek S, Wirth W, Ladel C, Hellio Le Graverand MP, Eckstein F.

Rates and sensitivity of knee cartilage thickness loss in specific central reading radiographic strata from the osteoarthritis initiative.

Osteoarthritis Cartilage. 2014 Oct ; 22(10):1550-3 / PMID: 25278063

4) Cotofana S, Buck R, Dreher D, Wirth W, Roemer F, Duryea J, Nevitt M, Eckstein F, Osteoarthritis Initiative Investigators.

Longitudinal (one-year) change in cartilage thickness in knees with early knee osteoarthritis: A within- person between-knee comparison.

Arthritis Care Res (Hoboken). 2014 Apr ; 66(4):636-41 / PMID: 24106150

5) Wirth W, Nevitt M, Hellio Le Graverand MP, Lynch J, Maschek S, Hudelmaier M, Eckstein F, OA Initiative Investigators Group.

Lateral and medial joint space narrowing predict subsequent cartilage loss in the narrowed, but not in the non-narrowed femorotibial compartment–data from the Osteoarthritis Initiative.

Osteoarthritis Cartilage. 2014 Jan ; 22(1):63-70 / PMID: 24185111

6) Cotofana S, Wyman BT, Benichou O, Dreher D, Nevitt M, Gardiner J, Wirth W, Hitzl W, Kwoh CK, Eckstein F, Frobell RB; OAI Investigators Group.

Relationship between knee pain and the presence, location, size and phenotype of femorotibial denuded areas of subchondral bone as visualized by MRI.

Osteoarthritis Cartilage. 2013 Sep ; 21(9):1214-22 / PMID: 23973133

7) Wirth W, Duryea J, Hellio Le Graverand MP, John MR, Nevitt M, Buck RJ, Eckstein F, OA Initiative Investigators Group.

Direct comparison of fixed flexion, radiography and MRI in knee osteoarthritis: responsiveness data from the Osteoarthritis Initiative.

Osteoarthritis Cartilage. 2013 Jan ; 21(1):117-25 / PMID: 23128183

8) Buck RJ, Wirth W, Dreher D, Nevitt M, Eckstein F.

Frequency and spatial distribution of cartilage thickness change in knee osteoarthritis and its relation to clinical and radiographic covariates – data from the osteoarthritis initiative.

Osteoarthritis Cartilage. 2013 Jan ; 21(1):102-9 / PMID: 23099212

9) Buck RJ, Dreher D, Eckstein F.

Femorotibial Cartilage Thickness Change Distributions for Subjects without Signs, Symptoms, or Risk Factors of Knee.

Osteoarthritis Cartilage. 2012 Oct ; 3(4):305-13 / PMID: 26069641

10) Guermazi A, Hunter DJ, Li L, Benichou O, Eckstein F, Kwoh CK, Nevitt M, Hayashi D.

Different thresholds for detecting osteophytes and joint space narrowing exist between the site investigators and the centralized reader in a multicenter knee osteoarthritis study–data from the Osteoarthritis Initiative.

Skeletal Radiol. 2012 Feb ; 41(2):179-86 / PMID: 21479521

11) Eckstein F, Cotofana S, Wirth W, Nevitt M, John MR, Dreher D, Frobell R; Osteoarthritis Initiative Investigators Group.

Greater rates of cartilage loss in painful knees than in pain-free knees after adjustment for radiographic disease stage: data from the osteoarthritis initiative.

Arthritis Rheum. 2011 Aug ; 63(8):2257-67 / PMID: 21520009

12) Wirth W, Buck R, Nevitt M, Le Graverand MP, Benichou O, Dreher D, Davies RY, Lee JH, Picha K, Gimona A, Maschek S, Hudelmaier M, Eckstein F; OAI Investigators.

MRI-based extended ordered values more efficiently differentiate cartilage loss in knees with and without joint space narrowing than region-specific approaches using MRI or radiography–data from the OA initiative.

Osteoarthritis Cartilage. 2011 Jun ; 19(6):689-99 / PMID: 21338702

13) Buck RJ, Wyman BT, Hellio Le Graverand MP, Hunter D, Vignon E, Wirth W, Eckstein F.

Using ordered values of subregional cartilage thickness change increases sensitivity in detecting risk factors for osteoarthritis progression.

Osteoarthritis Cartilage. 2011 Mar ; 19(3):302-8 / PMID: 21184835

14) Eckstein F, Nevitt M, Gimona A, Picha K, Lee JH, Davies RY, Dreher D, Benichou O, Le Graverand MP, Hudelmaier M, Maschek S, Wirth W; Osteoarthritis Initiative Investigators Group.

Rates of change and sensitivity to change in cartilage morphology in healthy knees and in knees with mild, moderate, and end-stage radiographic osteoarthritis: results from 831 participants from the Osteoarthritis Initiative.

Arthritis Care Res (Hoboken). 2011 Mar ; 63(3):311-9 / PMID: 20957657

15) Wirth W, Larroque S, Davies RY, Nevitt M, Gimona A, Baribaud F, Lee JH, Benichou O, Wyman BT, Hudelmaier M, Maschek S, Eckstein F; OA Initiative Investigators Group.

Comparison of 1-year vs 2-year change in regional cartilage thickness in osteoarthritis results from 346 participants from the Osteoarthritis Initiative.

Osteoarthritis Cartilage. 2011 Jan ; 19(1):74-83 / PMID: 21044690

16) Frobell RB, Nevitt MC, Hudelmaier M, Wirth W, Wyman BT, Benichou O, Dreher D, Davies R, Lee JH, Baribaud F, Gimona A, Eckstein F; Osteoarthritis Initiative Investigators.

Femorotibial subchondral bone area and regional cartilage thickness: a cross-sectional description in healthy reference cases and various radiographic stages of osteoarthritis in 1,003 knees from the Osteoarthritis Initiative.

Arthritis Care Res (Hoboken). 2010 Nov ; 62(11):1612-23 / PMID: 20496431

17) Eckstein F, Yang M, Guermazi A, Roemer FW, Hudelmaier M, Picha K, Baribaud F, Wirth W, Felson DT.

Reference values and Z-scores for subregional femorotibial cartilage thickness–results from a large population-based sample (Framingham) and comparison with the non-exposed Osteoarthritis Initiative reference cohort.

Osteoarthritis Cartilage. 2010 Oct ; 18(10):1275-83 / PMID: 20691798

18) Benichou OD, Hunter DJ, Nelson DR, Guermazi A, Eckstein F, Kwoh K, Myers SL, Wirth W, Duryea J; Osteoarthritis Initiative Investigators.

One-year change in radiographic joint space width in patients with unilateral joint space narrowing: data from the Osteoarthritis Initiative.

Arthritis Care Res (Hoboken). 2010 Jul ; 62(7):924-31 / PMID: 20589703

19) Eckstein F, Wirth W, Hunter DJ, Guermazi A, Kwoh CK, Nelson DR, Benichou O; OAI Investigators.

Magnitude and regional distribution of cartilage loss associated with grades of joint space narrowing in radiographic osteoarthritis– data from the Osteoarthritis Initiative (OAI).

Osteoarthritis Cartilage. 2010 Jun ; 18(6):760-8 / PMID: 20171298

20) Frobell RB, Wirth W, Nevitt M, Wyman BT, Benichou O, Dreher D, Davies RY, Lee JH, Baribaud F, Gimona A, Hudelmaier M, Cotofana S, Eckstein F; OA Initiative investigators.

Presence, location, type and size of denuded areas of subchondral bone in the knee as a function of radiographic stage of OA – data from the OA initiative.

Osteoarthritis Cartilage. 2010 May ; 18(5):668-76 / PMID: 20175972

21) Wirth W, Nevitt M, Hellio Le Graverand MP, Benichou O, Dreher D, Davies RY, Lee J, Picha K, Gimona A, Maschek S, Hudelmaier M, Eckstein F; OAI investigators.

Sensitivity to change of cartilage morphometry using coronal FLASH, sagittal DESS, and coronal MPR DESS protocols–comparative data from the Osteoarthritis Initiative (OAI).

Osteoarthritis Cartilage. 2010 Apr ; 18(4):547-54 / PMID: 20060948

22) Wirth W, Benichou O, Kwoh CK, Guermazi A, Hunter D, Putz R, Eckstein F; OAI Investigators.

Spatial patterns of cartilage loss in the medial femoral condyle in osteoarthritic knees: data from the Osteoarthritis Initiative.

Magn Reson Med. 2010 Mar ; 63(3):574-81 / PMID: 20146227

23) Eckstein F, Benichou O, Wirth W, Nelson DR, Maschek S, Hudelmaier M, Kwoh CK, Guermazi A, Hunter D; Osteoarthritis Initiative Investigators.

Magnetic resonance imaging-based cartilage loss in painful contralateral knees with and without radiographic joint space narrowing: Data from the Osteoarthritis Initiative.

Arthritis Rheum. 2009 Sep 15; 61(9):1218-25 / PMID: 19714595

24) Eckstein F, Wirth W, Hudelmaier MI, Maschek S, Hitzl W, Wyman BT, Nevitt M, Hellio Le Graverand MP, Hunter D; OA Initiative Investigator Group.

Relationship of compartment-specific structural knee status at baseline with change in cartilage morphology: a prospective observational study using data from the osteoarthritis initiative.

Arthritis Res Ther. 2009 ; 11(3):R90 / PMID: 19534783

25) Eckstein F, Maschek S, Wirth W, Hudelmaier M, Hitzl W, Wyman B, Nevitt M, Le Graverand MP; OAI Investigator Group.

One-year change of knee cartilage morphology in the first release of participants from the Osteoarthritis Initiative progression subcohort: association with sex, body mass index, symptoms and radiographic osteoarthritis status.

Ann Rheum Dis. 2009 May ; 68(5):674-9 / PMID: 18519425

26) Wirth W, Hellio Le Graverand MP, Wyman BT, Maschek S, Hudelmaier M, Hitzl W, Nevitt M, Eckstein F; OAI Investigator Group.

Regional analysis of femorotibial cartilage loss in a subsample from the Osteoarthritis Initiative progression subcohort.

Osteoarthritis Cartilage. 2009 Mar ; 17(3):291-7 / PMID: 18789729

In-vivo Femorotibial Compression Study (Pfizer)

1) Cotofana S, Eckstein F, Wirth W, Souza R, Li X, Wyman B, Hellio-Le Graverand M, Link T, Majumdar S.

In vivo measures of cartilage deformation patterns in healthy and osteoarthritic female knees using 3T MR imaging.

Eur Radiol. 2011 Jun ; 21(6):1127-35 / PMID: 21448616

2) Wirth W, Frobell RB, Souza RB, Li X, Wyman BT, Le Graverand MP, Link TM, Majumdar S, Eckstein F.

A three-dimensional quantitative method to measure meniscus shape, position, and signal intensity using MR images: a pilot study and preliminary results in knee osteoarthritis.

Magn Reson Med. 2010 May ; 63(5):1162-71 / PMID: 20432287

A 9001140 & A 9001191 3Tesla MRI Method Studies (Pfizer)

1) Eckstein F, Le Graverand MP, Charles HC, Hunter DJ, Kraus VB, Sunyer T, Nemirovskyi O, Wyman BT, Buck R; A9001140, investigators.

Clinical, radiographic, molecular and MRI-based predictors of cartilage loss in knee osteoarthritis.

Ann Rheum Dis. 2011 Jul ; 70(7):1223-30 / PMID: 21622772

2) Hudelmaier M, Wirth W, Wehr B, Kraus V, Wyman BT, Hellio Le Graverand MP, Eckstein F.

Femorotibial cartilage morphology: reproducibility of different metrics and femoral regions, and sensitivity to change in disease.

Cells Tissues Organs. 2010 ; 192(5):340-50 / PMID: 20606404

3) Buck RJ, Wyman BT, Le Graverand MP, Wirth W, Eckstein F; A9001140 Investigators.

An efficient subset of morphological measures for articular cartilage in the healthy and diseased human knee.

Magn Reson Med. 2010 Mar ; 63(3):680-90 / PMID: 20187178

4) Buck RJ, Wyman BT, Le Graverand MP, Hudelmaier M, Wirth W, Eckstein F; A9001140 investigators.

Osteoarthritis may not be a one-way-road of cartilage loss–comparison of spatial patterns of cartilage change between osteoarthritic and healthy knees.

Osteoarthritis Cartilage. 2010 Mar ; 18(3):329-35 / PMID: 19948267

5) Crema MD, Guermazi A, Li L, Nogueira-Barbosa MH, Marra MD, Roemer FW, Eckstein F, Le Graverand MP, Wyman BT, Hunter DJ.

The association of prevalent medial meniscal pathology with cartilage loss in the medial tibiofemoral compartment over a 2-year period.

Osteoarthritis Cartilage. 2010 Mar ; 18(3):336-43 / PMID: 19914195

6) Le Graverand MP, Buck RJ, Wyman BT, Vignon E, Mazzuca SA, Brandt KD, Piperno M, Charles HC, Hudelmaier M, Hunter DJ, Jackson C, Kraus VB, Link TM, Majumdar S, Prasad PV, Schnitzer TJ, Vaz A, Wirth W, Eckstein F.

Change in regional cartilage morphology and joint space width in osteoarthritis participants versus healthy controls: a multicentre study using 3.0 Tesla MRI and Lyon-Schuss radiography.

Ann Rheum Dis. 2010 Jan ; 69(1):155-62 / PMID: 19103634

7) Hellio Le Graverand MP, Buck RJ, Wyman BT, Vignon E, Mazzuca SA, Brandt KD, Piperno M, Charles HC, Hudelmaier M, Hunter DJ, Jackson C, Kraus VB, Link TM, Majumdar S, Prasad PV, Schnitzer TJ, Vaz A, Wirth W, Eckstein F.

Subregional femorotibial cartilage morphology in women–comparison between healthy controls and participants with different grades of radiographic knee osteoarthritis.

Osteoarthritis Cartilage. 2009 Sep ; 17(9):1177-85 / PMID: 19341831

8) Hunter DJ, Buck R, Vignon E, Eckstein F, Brandt K, Mazzuca SA, Wyman BT, Otterness I, Hellio Le Graverand MP.

Relation of regional articular cartilage morphometry and meniscal position by MRI to joint space width in knee radiographs.

Osteoarthritis Cartilage. 2009 Sep ; 17(9):1170-6 / PMID: 19401243

9) Buck RJ, Wyman BT, Le Graverand MP, Hudelmaier M, Wirth W, Eckstein F; A9001140 Investigators.

Does the use of ordered values of subregional change in cartilage thickness improve the detection of disease progression in longitudinal studies of osteoarthritis?

Arthritis Rheum. 2009 Jul 15; 61(7):917-24 / PMID: 19565557

10) Eckstein F, Wyman BT, Buck RJ, Wirth W, Maschek S, Hudelmaier M, Le Graverand MP; A9001140 Study Group.

Longitudinal quantitative MR imaging of cartilage morphology in the presence of gadopentetate dimeglumine (Gd-DTPA).

Magn Reson Med. 2009 Apr ; 61(4):975-80 / PMID: 19215048

11) Eckstein F, Buck RJ, Burstein D, Charles HC, Crim J, Hudelmaier M, Hunter DJ, Hutchins G, Jackson C, Kraus VB, Lane NE, Link TM, Majumdar LS, Mazzuca S, Prasad PV, Schnitzer TJ, Taljanovic MS, Vaz A, Wyman B, Le Graverand MP; A9001140 Study Group.

Precision of 3.0 Tesla quantitative magnetic resonance imaging of cartilage morphology in a multicentre clinical trial.

Ann Rheum Dis. 2008 Dec ; 67(12):1683-8 / PMID: 18283054

12) Eckstein F, Buck RJ, Wyman BT, Kotyk JJ, Le Graverand MP, Remmers AE, Evelhoch JL, Hudelmaier M, Charles HC.

Quantitative imaging of cartilage morphology at 3.0 Tesla in the presence of gadopentate dimeglumine (Gd-DTPA).

Magn Reson Med. 2007 Aug ; 58(2):402-6 / PMID: 17654593

13) Eckstein F, Charles HC, Buck RJ, Kraus VB, Remmers AE, Hudelmaier M, Wirth W, Evelhoch JL.

Accuracy and precision of quantitative assessment of cartilage morphology by magnetic resonance imaging at 3.0T.

Arthritis Rheum. 2005 Oct ; 52(10):3132-6 / PMID: 16200592

Academic Grants

Academic Grants, Subcontracts & Services, Software & Training, and Data Sharing Agreements for Medical Image Analysis by Chondrometrics GmbH since its Foundation in 2003.
More recent contracts are listed on the top; industry contracts are not included.
The pie chart below displays the number of projects per country (percent of total in brackets) from where funding was obtained (63 projects in total).
Pie Chart Showing the Number of Academic Projects since 2003 per Country (n=63)

Detailed list of the above academic grantsIn kind contribution, Imperial College, London, England, 2025-2026Felix Eckstein and Wolfgang Wirth, provider of medical image analysis service, and Neal Bangerter and Krithika Balaji, Imperial College London, principal investigator and PhD of the funded project.qDESS vs. Phase-Cycled bSSFP for 3T cartilage imaging: Segmentation, morphometry, and T₂ mapping.

ESA AO-2019-ISS_PP_058 Grant renewed, European Space Agency, through the German Ministry of Economic Affairs and Climate Action (BMWK), Berlin, Germany (Cartilage Degeneration Project); 2023 – 2026
Felix Eckstein, co-investigator with Anna-Maria Liphardt, Universitätsklinikum Erlangen und Friedrich-Alexander-Universität Erlangen-Nürnberg (#50WB2021), and with Anja Niehoff, Deutsche Sporthochschule Köln (#50WB2022), principal investigators of the project.
Pre- and post-flight experiments using the International Space Station (ISS) environment: Joint health during a one-year mission to the ISS – an assessment of relevance for exploration
ESA AO-20-BR_009 Grant renewed, European Space Agency, through the German Ministry of Economic Affairs and Climate Action (BMWK), Berlin, Germany (Joint Health Project); 2023 – 2026
Felix Eckstein, co-investigator with Anja Niehoff, Deutsche Sporthochschule Köln (#50WB2022), and Anna-Maria Liphardt, Universitätsklinikum Erlangen und Friedrich-Alexander-Universität Erlangen-Nürnberg (#50WB2021), principal investigators of the project.
Opportunity soliciting human research proposals for bedrest studies (BRACE und BRAVE)
SNF 320030/184912 Grant, University of Basel, Switzerland; 2022-2024
Felix Eckstein, provider of medical image analysis service, and Annegret Mündermann, University of Basel, principal investigator of the study.
Analysis of knee cartilage in younger and older participants with or without previous unilateral ACL injury
#E! 114932 EU Grant, Eurostars-2 joint program, with 4P Pharma, Lille, France; 2021-2024
Co-funding from the European Union Horizon 2020 research and innovation program, with the project management agency (Deutsches Zentrum für Luft- und Raumfahrt) acting on behalf of the Federal Ministry of Education and Research (BMBF). Felix Eckstein & Wolfgang Wirth, work package leads, and Francis Berenbaum, 4P Pharma, principal investigator of the project.
Lebensverändernde Behandlung für Osteoarthrose-PatientInnen: Ein Biomarker-basierter Lösungsansatz: Teilprojekt: Entwicklung innovativer Bildgebungs-Biomarker für klinische Osteoarthrose-Studien (OA BIO Consortium study)
DU PO 1001473784, University of Colorado, Denver, CO, USA; 2021-2024 Felix Eckstein, provider of medical image analysis service, and Jason Dragoo, University of Denver.
Image analysis with Chondrometrics software in a stem cell chondral defect study and in an osteoarthritis stem cell trial
ICL PO, Imperial College, London, England; 2021-2023
Felix Eckstein and Wolfgang Wirth, provider of medical image analysis service, and Neal Bangerter, Imperial College London, principal investigator of the project.
Sample cartilage segmentations at 7 Tesla for generating deep learning models facilitating automated cartilage analysis.
NHMRC Grant APP1162874, University of Sydney, Australia; 2020-2025.
Felix Eckstein, provider of clinical trial service, and David Hunter, University of Sydney, principal investigator of the study.
Stem Cell injections for symptomatic relief and strUctural improvement in people with Tibiofemoral knee OsteoaRthritis (The SCUlpTOR trial))
RUG PO, Stichting Ortho Research Center, UniversityGroningen, The Netherlands; 2020-2022
Wolfgang Wirth & Felix Eckstein, provider of medical image analysis service, and Astrid de Vries, coordinator of the project.
Use of orthoses in knee osteoarthritis
ESA AO-2019-ISS_PP_058 Grant, European Space Agency, through the German Ministry of Economic Affairs and Climate Action (BMWK), Berlin, Germany (Cartilage Degeneration Project); 2019 – 2023
Felix Eckstein, co-investigator with Anna-Maria Liphardt, Universitätsklinikum Erlangen und Friedrich-Alexander-Universität Erlangen-Nürnberg (#50WB2021), and with Anja Niehoff, Deutsche Sporthochschule Köln (#50WB2022), principal investigators of the project.
Pre- and post-flight experiments making use of the International Space Station (ISS) environment
ESA AO-20-BR_009 Grant, European Space Agency, through the German Ministry of Economic Affairs and Climate Action (BMWK), Berlin, Germany (Joint Health Project); 2019 – 2023
Felix Eckstein, co-investigator with Anja Niehoff, Deutsche Sporthochschule Köln (#50WB2022), and Anna-Maria Liphardt, Universitätsklinikum Erlangen und Friedrich- Alexander-Universität Erlangen-Nürnberg (#50WB2021), principal investigators of the project.
Opportunity soliciting human research proposals for bedrest studies (BRACE und BRAVE)
FNIH Goods & Service Agreement, Foundation for the National Institutes of Health, Bethesda, MD, USA; 2019-2021
Felix Eckstein, principal investigator of the service agreement, and Virginia Kraus, Duke University, Durham, NC, USA & David Hunter, University of Sydney, Sydney, NSW, Australia, principal investigators of the project.
Imaging biomarker analysis service for the Progress OA study (FNIH2)
ZonMW Grant 95110008, The Netherlands Organization for Health Research and Development, University Medical Center Utrecht, The Netherlands; 2019-2020
Felix Eckstein, subcontractor, and Floris Lafeber, University Medical Center Utrecht, principal investigator of the project.
Joint distraction in treatment of end-stage knee osteoarthritis – Cartilage morphometry in two randomized controlled trials of patients with high tibial osteotomy (HTO) and knee joint distraction (KJD).
SU Data Sharing Agreement between Chondrometrics GmbH and Stanford University, CA, USA; 2019-2020
Felix Eckstein and Akshay Chaudhari, Department of Radiology, Standford University, Co-PI of the project.
A machine- (deep-) learning approach to fully automated regional bone, cartilage and phenotype analysis in knees osteoarthritis – development, validation, application, and qualification
DSHS PO 4500001636, Deutsche Sporthochschule Köln, Germany; 2019-2020
Felix Eckstein, provider of medical image analysis software and training, and Peter Brüggemann, Deutsche Sporthochschule Köln, principal investigator of the study.
Measurement of cartilage properties in relation to the use of footwear
UWO PO 181229, University of Western Ontario, London, Canada; 2018-2024
Felix Eckstein, provider of medical image analysis service (articular cartilage morphology and transverse relaxation time), and Trevor Birmingham, University of Western Ontario, principal investigator of the project.
Longitudinal analysis of cartilage MRI properties before and after high tibial osteotomy (HTO).
EU IMI2 Grant 115770 (Subcontract), European Union Innovative Medicines Initiative (IMI) by University Medical Center Utrecht, The Netherlands; 2018-2021
Felix Eckstein, principal investigator of the subcontract, and Harry Weinans, University Medical Center Utrecht, principal investigator of the work package.
Applied public-private research enabling osteoarthritis clinical headway (APPROACH study).
PO DFKI IIP-EXTREM, Deutsches Forschungszentrum für Künstliche Intelligenz, Kaiserslautern, Germany; 2018-2020
Felix Eckstein, provider of medical image analysis service, and Christian Schlinkmann, Deutsches Forschungszentrum für Künstliche Intelligenz.
Segmentation of anatomical structures of the thigh and shank from magnetic resonance images (MRIs) for the generation of automated models for generating personalized prostheses.
SU PO 61913492, Stanford University, Redwood City, CA, USA; 2018-2020 Felix Eckstein, provider of medical image analysis service, and Jason Dragoo, Department of Orthopaedic Surgery, Stanford University.
Quantitative analysis of femoral cartilage in a stem cell chondral defect study and in an osteoarthritis stem cell trial
Investigator Initiated Co-Funding Project (IIP) between Chondrometrics GmbH and Merck KGaA, Germany; 2018-2019
Felix Eckstein, PI of the IIP, and Christoph Ladel, Merck KGaA, Co-PI of the project.
Determination of thresholds of progression from the healthy reference cohort of the Osteoarthritis Initiative (OAI) with coronal FLASH and sagittal DESS imaging
NTUST PO, National University of Science and Technology, Taipeh, Taiwan; 2018-2019
Felix Eckstein, provider of medical image analysis service, and Wei-Chun Hsu, Graduate Institute of Biomedical Engineering Taipei, principal investigator of the project.
Study of an athletic population with unilateral symptomatic osteoarthritis.
DFG Grant NE 2136/3-1, 701010997 Deutsche Forschungsgemeinschaft, Universitätsklinikum Düsseldorf, Germany; 2018-2019
Felix Eckstein, provider of medical image analysis service, and Sven Nebelung, University Düsseldorf, principal investigator of the project.
Functional and biomechanical methods using multi-parametric MRI for early detection of osteoarthritis.
SU PO 61763686, Stanford University, Palo Alto, CA, USA; 2018-2019
Felix Eckstein, provider of medical image analysis service, and Constance Chu, Stanford University, principal investigator of the study.
Femoral cartilage transverse relaxation time (T2) in an academic trial on effects of unloader bracing on clinical outcome and articular cartilage regeneration following microfracture of isolated chondral defects.
Investigator Initiated Co-Funding Project (IIP) between Chondrometrics GmbH and Merck KGaA, Germany; 2017-2018
Felix Eckstein, PI of the IIP, and Christoph Ladel, Merck KGaA, Co-PI of the project.
Prediction of incident radiographic osteoarthritis by 3D meniscus morphology and position properties from MRI, in knees with early osteoarthritis (KLG1)
SickKids PO REB FN10000010841, Hospital for Sick Children, Toronto, Canada; 2016-2017
Felix Eckstein, provider of medical image analysis service, and Andrea Doria, Hospital for Sick Children, principal investigator of the study.
Analysis of ankle cartilage in patients with hemophilia and controls
Investigator Initiated Co-Funding Project (IIP) between Chondrometrics GmbH and Merck KGaA, Germany; 2016-2017
Felix Eckstein, PI of the IIP, and Martin Michaelis, Merck KGaA, Co-PIs of the project.
Prediction of incident radiographic osteoarthritis by cartilage composition (MRI transverse relaxation time) in knees with early osteoarthritis (KLG1)
ESA Res. Announcement ILSRA-2009-BR-0994 & German Federal Ministry for Economic Affairs (BWi) 50WB1520 Grant, Berlin, Germany; 2015-2019.
Felix Eckstein, co-investigator with Anja Niehoff, Deutsche Sporthochschule Köln, principal investigator of the project.
The effects of microgravity on cartilage morphology and biology
BMBF 01EC1408D Grant, Research network musculoskeletal diseases, 2015 – 2019
Federal Ministry of Education and Research (BMBF), Felix Eckstein & Wolfgang Wirth, co-PIs of a work package, and Georg Duda, Charite Berlin, PI of the project
OVERLOAD-PrevOP – Verständnis und Prävention der Progression der primären Osteoarthrose
UTAS Research Enhancement Grant, University of Tasmania, Hobart, Australia; 2015-2016 Felix Eckstein, provider of medical image analysis service; and Benny EathakkattuAntony, University of Tasmania, principal investigator of the grant.
Associations of physical activity, physical performance measures and obesity in childhood with knee cartilage thickness in adults after 25 years
Canadian Institute of Health Research (CIHR) Grant, University of Western Ontario, London, Canada; 2014-2019.
Felix Eckstein, provider of medical image analysis software and training, and Trevor Birmingham, University of Western Ontario, principal investigator of the project.
Load-altering interventions and knee osteoarthritis progression.
SickKids PO REB FN 10000010841, Hospital for Sick Children, Toronto, Canada; 2014-2015
Felix Eckstein, provider of medical image analysis service, and Andrea Doria, Hospital for Sick Children, principal investigator of the study.
Measurement properties of ultrasound for assessment of hemophilic arthropathy: MRI correlation
DHS PO 13-20, Deutsche Sporthochschule, Köln, Germany; 2013-2015
Felix Eckstein, provider of medical image analysis software and training, and Anja Niehoff, Deutsche Sporthochschule Köln, principal investigator of the study.
Measurement of knee cartilage morphology in biomechanically relevant studies
Investigator Initiated Co-Funding Project (IIP) between Chondrometrics GmbH and Merck KGaA, Germany; 2013-2014
Felix Eckstein, PI of the IIP, and Christoph Ladel, Merck KGaA, Co-PI of the project.
Predictive value of imaging biomarkers (cartilage morphology at T-3 and T-1) on risk of total knee replacement at 48-60 months in the Osteoarthritis Initiative (OAI)
NIH P60 Grant AR047785, Multidisciplinary clinical research center (MCRC); National Institutes of Health, Bethesda, USA; 2012-2017 Felix Eckstein, principal investigator of subcontract; David Felson, Boston University, Boston, MA, USA, principal investigator of the grant.
Effect of bariatric surgery on knee structure and pain (OABS study)
FNIH Goods & Service Agreement, Foundation for the National Institutes of Health, Bethesda, MD, USA; 2012-2014
Felix Eckstein, principal investigator of the service agreement, and Virginia Kraus, Duke University, Durham, NC, USA & David Hunter, University of Sydney, Sydney, NSW, Australia, principal investigators of the project.
Imaging biomarker analysis service for the Osteoarthritis Initiative (OAI) Biomarker Consortium Study (FNIH1)
Investigator Initiated Co-Funding Project (IIP) between Chondrometrics GmbH and Merck KGaA, Germany; 2012-2013
Felix Eckstein, PI of the IIP, and Christoph Ladel, Merck KGaA, Co-PI of the project.
Longitudinal analysis of cartilage morphology in the in the OAI healthy reference cohort and in the Foundation of NIH OAI Biomarker Consortium Sample (cont.).
RN LLP-9 Grant, ReumaNederland (Dutch Arthritis Society), The Netherlands; 2011-2016
Felix Eckstein, subcontractor, and Floris Lafeber, University Medical Center Utrecht, principal investigator of the project.
Mechanisms of tissue degeneration and regeneration in rheumatic diseases with focus on joint distraction therapy in osteoarthritis.
FHS USYD PO, Faculty of Healthy Sciences, University of Sydney; Australia 2011-2012
Felix Eckstein, provider of medical image analysis software and training, and Marlene Fransen, University of Sydney, principal investigator of the study.
Longitudinal measurement of knee cartilage morphometry using MR imaging, to evaluate the benefit of glucosamine sulfate, with and without chondroitin sulfate, for people with symptomatic knee osteoarthritis in terms of structural knee progression.
NIH NHLBI Grant HHSN26820100002, National Institutes of Health & National Heart, Lung, and Blood Institute, Bethesda, MD, USA; 2010-2015 Felix Eckstein, principal investigator of the subcontract, Kent Kwoh, University of Pittsburgh, PA, USA, principal investigator of the project.
Pivotal Osteoarthritis Initiative MRI Analyses (the POMA study)
Investigator Initiated Co-Funding Project (IIP) between Chondrometrics GmbH and Novartis Pharma AG, Basel, Switzerland; 2010-2011
Felix Eckstein, PI of the IIP, and Markus John, Novartis Pharma AG, Co-PI of the project.
Prognostic value of clinical, serological and imaging biomarkers on risk of total knee replacement (TKR): a prospective observational cohort study in patients with knee osteoarthritis.
Investigator Initiated Co-Funding Project (IIP) between Chondrometrics GmbH and Merck KGaA, Germany; 2010-2011
Felix Eckstein, PI of the IIP, and Christoph Ladel, Merck KGaA, Co-PI of the project.
Longterm (4-year) longitudinal analysis of cartilage morphology change in the Foundation of NIH (FNIH) OAI Biomarker Consortium Sample
NIH R01 Grant AR054806, National Institutes of Health, Bethesda, MD, USA; 2009-2013 Felix Eckstein, principal investigator of the subcontract, and Leena Sharma, Northwestern University, Chicago, MI, USA, principal investigator of the project.
Relationship of hip muscle group weakness to deterioration of the OA knee by MRI
Investigator Initiated Project (IIP OAI No8) between Chondrometrics GmbH and Novartis Pharma AG, Basel, Switzerland, 2008-2009
Felix Eckstein, PI of the IIP, and Alberto Gimona, Novartis Pharma AG, Co-PI of the project.
Advanced radiographic disease (KLG 4) two- (and one-) year longitudinal analysis of cartilage morphology change in a sample of the Osteoarthritis Initiative
Investigator Initiated Project (IIP OAI No7) between Chondrometrics GmbH and Centocor Inc. R&D, USA; 2008-2009
Felix Eckstein, PI of the IIP, and Frederic Baribaud, Centocor R&D, Co-PI of the project.
Healthy reference cohort analysis of longitudinal change in cartilage morphology in the Osteoarthritis Initiative
Investigator Initiated Project (IIP OAI No6) between Chondrometrics GmbH and Wyeth Co, USA; 2008-2009
Felix Eckstein, PI of the IIP, and Jennifer Lee, Wyeth, Co-PI of the project.
Subregion analysis of two- (and one-) year longitudinal change in cartilage morphology in the Osteoarthritis Initiative.
Investigator Initiated Project (IIP OAI No5) between Chondrometrics GmbH and the Osteoarthritis initiative (OAI) Coordinating Center (UCSF Vendor Contract 9000011523), University of California, San Francisco, CA, USA; 2008-2009
Felix Eckstein and Michael Nevitt, University of California San Francisco, co-principal investigators of the project.
Two- (and one-) year longitudinal analysis of cartilage morphology in a further sample of the Osteoarthritis Initiative using sagittal double echo steady state MRI
Investigator Initiated Project (IIP OAI No4) between Chondrometrics GmbH and GlaxoSmithKline (“GSK”), USA; 2008-2009
Felix Eckstein, PI of the IIP, and Dominique Ethgen, GlaxoSmithKline, Co-PI of the project.
Two-year longitudinal analysis of cartilage morphology in a further sample of the Osteoarthritis Initiative using coronal spoiled gradient echo MRI.
Investigator Initiated Project (IIP OAI No3) between Chondrometrics GmbH and Merck Serono, Switzerland; 2008-2009
Felix Eckstein, PI of the IIP, and Alberto Gimona, Merck Serono, Co-PI of the project.
One-year longitudinal analysis of cartilage morphology change in a further sample of the Osteoarthritis Initiative, using coronal spoiled gradient echo MRI.
Investigator Initiated Project (IIP OAI No2) between Chondrometrics GmbH and Eli Lilly & Co, USA; 2007-2008
Felix Eckstein, PI of the IIP, and Olivier Benichou, Eli Lilly & Co, Co-PI of the project.
One-year longitudinal analysis of side-differences in cartilage morphology change in subjects from the Osteoarthritis Initiative with uni-lateral radiographic joint space narrowing, using from sagittal dual echo steady state (DESS) MRI.
Investigator Initiated Project (IIP OAI No1) between Chondrometrics GmbH and Pfizer Inc., USA; 2006-2008
Felix Eckstein, PI of the IIP, and Marie-Pierre Hellio Le Graverand, Pfizer Inc., Co-PI of the project.
One-year longitudinal analysis of cartilage morphology change in a first progressor sample of the Osteoarthritis Initiative using coronal spoiled gradient echo MRI.
NIH P60 MCRC Grant AR048098, National Institutes of Health, Bethesda, MD, USA; 2006-2012
Felix Eckstein, principal investigator of the subcontract, Leena Sharma, Northwestern University, Chicago, MI, USA, principal investigator of the project & Richard Pope, Northwestern University, principal investigator of the Multidisciplinary Clinical Research Center.
Potential Beneficial Role of Hip Muscles in Knee Osteoarthritis.
UCSF Vendor Contract 9000011523, Osteoarthritis Initiatives (OAI) Coordinating Center, University of California,, San Francisco, CA, USA; 2006-2008Felix Eckstein, principal investigator of the subcontract, with Michael Nevitt, University of California, San Francisco, principal investigator of the project.
Baseline, 12, and 24 month quantitative cartilage analysis in a sample of Osteoarthritis Initiative index knees (OAI)
NIH RO1 Grant AR052528-01A2 National Institutes of Health, Bethesda, MD, USA; 2006-2011
Felix Eckstein, principal investigator of the subcontract, and Stephen Messier, Wake Forest University, Winston Salem, NC, USA, principal investigator of the project.
Intensive dietary restriction with exercise in arthritis (IDEA trial)
ACRIN Grant, American College of Radiology, USA; 2006-2008:
Felix Eckstein, principal investigator of the sucontract, with Timothy Mosher, Pennsylvania State University, PA, USA, principal investigator of the project.
Reproducibility & stability of cartilage morphology measures with 3 Tesla MRI.
RNSH PO, Institute of Bone and Joint Research, Royal North Shore Hospital, Sydney, Australia; 2006-2008.
Felix Eckstein, provider of medical image analysis software and training, and Lyn March, Royal North Shore Hospital, principal investigator of the study.
Measurement of cartilage morphology for assessing the effect of weight loss on knee joint structure in patients undergoing two different weight loss programs.
USYD PO, School of Exercise and Sport Science, University of Sydney, Australia; 2006-2008.
Felix Eckstein, provider of medical image analysis software and training, and Benedicte Vanwanseele, School of Exercise and Sport Science; principal investigator of the study.
Relationship of cartilage/meniscus morphology with gait biomechanics parameters in women with knee osteoarthritis
NIH R01 Grant AR52918, National Institutes of Health, Bethesda, MD, USA; 2005-2010
Felix Eckstein, principal investigator of the subcontract, and Leena Sharma, Northwestern University, Chicago, MI, USA, principal investigator of the project.
Ancillary study to the Osteoarthritis Initiative (OAI)
DSHS PO 100202, Deutsche Sporthochschule, Köln, Germany; 2005-2007
Felix Eckstein, provider of medical image analysis software and training, and Peter Brüggemann, Sporthochschule Köln, principal investigator of the study.
Knee joint cartilage morphology in athletes before, and after specific impact exercise protocols, and comparison with physically inactive volunteers
McM PO, McMaster University, Hamilton, Canada; 2005-2007
Felix Eckstein, provider of medical image analysis software and training, and Karen Beattie, Department of Medicine, McMaster University, Hamilton, ON, Canada; investigator of the study.
Comparison of quantitative cartilage parameters in healthy and arthritic knees and comparison with minimum joint space width on fixed flexion radiographs. from MR images in paraplegic patients versus controls
NIH RO1 Grant HD043500, National Institutes of Health, Bethesda, MD, USA; 2005-2007
Felix Eckstein, principal investigator of the subcontract, and Leena Sharma, Northwestern University, Chicago, MI, USA, principal investigator of the project.
Laxity and malalignment in a large cohort study of OA (MOST study)
CFI (Canada Foundation for Innovation) infrastructure grant; University of British Columbia, Vancouver; 2004-2007.
Felix Eckstein, provider of medical image analysis software and training, and David Wilson, University of British Columbia, principal investigator of the study. Measurement of cartilage morphometric properties from MR images of the human hip and shoulder
NIH funded UCSF Vendor Contract, Osteoarthritis Initiatives (OAI) Coordinating Center, University of California, San Francisco, CA, USA, by the National Institutes of Health, Bethesda, MD, USA; 2004-2005
Felix Eckstein, principal investigator of the subcontract, with Michael Nevitt, University of California, San Francisco, principal investigator of the project.
Test-retest cartilage volume analysis for cross validation and coil comparison in the Osteoarthritis Initiative (OAI) pilot study.
NIH RO1 Grant AR48216 National Institutes of Health, Bethesda, MD, USA; 2003-2007
Felix Eckstein, principal investigator of the subcontract, and Leena Sharma, Northwestern University, Chicago, principal investigator of the project.
Progression of knee OA: The role of local factors (the MAK study).
NIH P60 Center Grant AR47785, National Institutes of Health, Bethesda, MD, USA; 2003-2006
Felix Eckstein, principal investigator of the subcontract, and David Felson, Boston University, Boston, MA, USA, principal investigator of the project.
Correlates of a rticular cartilage thickness in knees of subjects in the Framingham study.
AF Clinical Sciences Grant, Arthritis Foundation, Atlanta, GA, USA; 2003-2006
Felix Eckstein, principal investigator of the subcontract, and David Felson, Boston University, Boston, MA, USA, principal investigator of the project.
Correlates of articular cartilage volume and thickness in Framingham subjects.

Exclusive Executive Summaries

In our Exclusive Executive Summaries section, we are synthesizing series of current publications around focus topics. These “mini-reviews” provide short overviews over key areas of interest, as well as archives for downloading PDFs of the relevant articles (click the reference# to download the pdf [when available open access]).
Enjoy reading and do not hesitate to contact us for questions or further discussion.

The Sprifermin ProgramSeveral Original Articles published 2013-2021 provide exciting insights into the structural benefits observed with Sprifermin in the Phase I, IIa, and IIb study.

The Sprifermin program is unique amongst potential disease modifying osteoarthritis drug (DMOAD) trials, as it encompasses several large multicenter randomized control trials, providing a tremendously rich resource for designing future DMOAD trials. With 5-year follow-up, FORWARD (Phase IIb) was the longest OA trial, using MR imaging, to date.
The phase I “First in Man” (FIH) randomized control trial (RCT) studied the safety and potential efficacy of intra-articular sprifermin (rhFGF18) in 73 knee osteoarthritis (KOA) patients, scheduled for knee replacement. The study was suggestive of an anabolic effect on medial femorotibial cartilage, and of a reduction of knee replacement rates, without these observations reaching statistical significance (1).

In the following phase IIa “Proof of Concept” POC study, 192 KOA patients were randomized to placebo or 1 of 3 sprifermin doses, injected 3 times over 3 weeks, and the same set of injects again 3 months later (2). In this study, the dose-response in the primary structural endpoint (central medial femorotibial cartilage thickness) was distinguishable, but did not reach statistical significance, at months 3, 6 or 12 follow-up. However, rhFGF18 significantly increase cartilage thickness in the lateral and total (medial and lateral) femorotibial compartment relative to placebo-injected knees (2). There was a substantial reduction in knee pain in all study participants over 12 months, but no statistically significant effect of rhFGF18 in this study relative to placebo. Location-independent analysis of cartilage thickness change (see another Executive Summary on this Page) revealed that rhFGF18 not only increased cartilage thickness (at potentially non-useful locations in the joint), but effectively reduced cartilage loss (3).

In the phase IIb study (FGF-18 Osteoarthritis Randomized Trial with Administration of Repeated Doses / FORWARD), 549 participants were randomized to 4 dose and 1 placebo group, with injection cycles at screening, 6,12, and 18 months (4). The patients included displayed Kellgren Lawrence Grade (KLG) 2-3 (medial or lateral disease), with a medial radiographic joint space width (JSW) of >2.5mm. This study found a statistically significant dose-dependent effect on the primary endpoint (total femorotibial cartilage thickness) as well as the central medial femorotibial subregion at year 2 and 3 (4), but no effect on medial radiographic JSW. Reduction in WOMAC pain (approximately 50%) was again seen in all 5 groups, but not statistically significantly greater than in placebo (4). Post-hoc analysis using location-independent measurement technology (see above) demonstrated a doubling of the cartilage thickening score over 2y with the highest sprifermin dose compared with placebo and with healthy Osteoarthritis Initiative (OAI) reference subjects. There also was a significant reduction of the cartilage thinning score to -0.43mm with the highest sprifermin dose, compared with -0.77mm in placebo and with -0.34mm in healthy reference subjects from the OAI (5).

Pertinent with the inclusion criteria, only a small number of FORWARD participants displayed advanced KOA. In a post-hoc analysis of a subcohort at risk (SAR) (6) that included the patients with more severe radiographic disease and pain, femorotibial cartilage thickness gain with the highest sprifermin dose vs. placebo was as high as for the total cohort (0.06 and 0.05 mm at 2 and 3y, respectively) (6) . In this cohort, with clinically and structurally advanced disease, sprifermin treatment translated into a statistically significant and clinically relevant benefit with the highest dose vs. placebo (-8.75 on a 0-100 WOMAC pain scale vs. only 0.97 for the total cohort) (6) . These findings suggest that the anabolic effect on cartilage is not less pronounced in advanced vs. early KOA, whereas translation of structure modification to symptom benefit appears to be more likely when KOA has progressed further.

The 5-year follow-up in FORWARD confirmed that post-treatment cartilage loss was similar amongst the sprifermin- and placebo-treated participants, and that the structural benefit achieved during the treatment period (0.05 mm total femorotibial cartilage thickness between the highest sprifermin dose group vs. placebo) was maintained for another 3 years (7). These findings suggest that the cartilage produced with induction of sprifermin appears to withstand in a normal mechanical environment and provide a lasting benefit after cessation of treatment (7). After 5 years, this structural benefit was also maintained in the SAR, with translation of structure modification into a clinical benefit still apparent after year 5 (7).

More studies pending publication, also see News Section for recent conference contributions

Citation References

1. Dahlberg LE, Aydemir A, Muurahainen N, Gühring H, Fredberg Edebo H, Krarup-Jensen N, et al.
A first-in-human, double-blind, randomised, placebo-controlled, dose ascending study of intra-articular rhFGF18 (sprifermin) in patients with advanced knee osteoarthritis.
Clin Exp Rheumatol 2016;34:445–50.

2. Lohmander LS, Hellot S, Dreher D, Krantz EFW, Kruger DS, Guermazi A, et al.
Intraarticular sprifermin (recombinant human fibroblast growth factor 18) in knee osteoarthritis: a randomized, double-blind, placebo-controlled trial.
Arthritis Rheumatol (Hoboken, NJ) 2013;66:1820–1831.

3. Eckstein F, Wirth W, Guermazi A, Maschek S, Aydemir A.
Intra-articular sprifermin not only increases cartilage thickness, but also reduces cartilage loss – location-independent post hoc analysis using MR imaging.
Arthritis Rheumatol 2015;67:2916–2922.

4. Hochberg MC, Guermazi A, Guehring H, Aydemir A, Wax S, Fleuranceau-Morel P, et al.
Effect of Intra-Articular Sprifermin vs Placebo on Femorotibial Joint Cartilage Thickness in Patients With Osteoarthritis.
JAMA 2019;322:1360–1370.

5. Eckstein F, Wax S, Aydemir A, Wirth W, Maschek S, Hochberg M.
Intra-articular sprifermin reduces cartilage loss in addition to increasing cartilage gain independent of femorotibial location: a post-hoc analysis of a randomized, placebo-controlled phase ii clinical trial.
Ann Rheum Dis 2020;79:525–528.

6. Guehring H, Moreau F, Daelken B, Ladel C, Guenther O, Bihlet AR, et al.
The effects of sprifermin on symptoms and structure in a subgroup at risk of progression in the FORWARD knee osteoarthritis trial.
Semin Arthritis Rheum 2021;51:450–456.

7. Eckstein F, Hochberg MC, Guehring H, Moreau F, Ona V, Bihlet AR, et al.
Long-term structural and symptomatic effects of intra-articular sprifermin in patients with knee osteoarthritis: 5-year results from the FORWARD study.
Ann Rheum Dis 2021;80:1062–1069.