Chondrometrics GmbH

Ainring, Germany

Chondrometrics GmbH

Ainring, Germany
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Messier S.P.,Wake forest University | Mihalko S.L.,Wake forest University | Miller G.D.,Wake forest University | Nicklas B.J.,Wake forest University | And 8 more authors.
JAMA - Journal of the American Medical Association | Year: 2013

IMPORTANCE: Knee osteoarthritis (OA), a common cause of chronic pain and disability, has biomechanical and inflammatory origins and is exacerbated by obesity. OBJECTIVE: To determine whether a ≥10% reduction in body weight induced by diet, with or without exercise, would improve mechanistic and clinical outcomes more than exercise alone. DESIGN, SETTING, AND PARTICIPANTS: Single-blind, 18-month, randomized clinical trial at Wake Forest University between July 2006 and April 2011. The diet and exercise interventions were center-based with options for the exercise groups to transition to a home-based program. Participants were 454 overweight and obese older community-dwelling adults (age ≥55 years with body mass index of 27-41) with pain and radiographic knee OA. INTERVENTIONS: Intensive diet-induced weight loss plus exercise, intensive diet-induced weight loss, or exercise. MAIN OUTCOMES AND MEASURES: Mechanistic primary outcomes: knee joint compressive force and plasma IL-6 levels; secondary clinical outcomes: self-reported pain (range, 0-20), function (range, 0-68), mobility, and health-related quality of life (range, 0-100). RESULTS: At 18 months, 399 participants (88%) completed the study. Compared with exercise participants, knee compressive forces were lower in diet participants and IL-6 levels were lower in diet and diet + exercise participants. (Table Presented) CONCLUSIONS AND RELEVANCE: Among overweight and obese adults with knee OA, after 18 months, participants in the diet + exercise and diet groups had more weight loss and greater reductions in IL-6 levels than those in the exercise group; those in the diet group had greater reductions in knee compressive force than those in the exercise group. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00381290.


Buck R.J.,StatAnswers Consulting LLC | Wirth W.,Paracelsus Medical University | Wirth W.,Chondrometrics GmbH | Dreher D.,MerckSerono S.A. | And 3 more authors.
Osteoarthritis and Cartilage | Year: 2013

Objective: Estimate the frequency and spatial location of rapid femorotibial cartilage thinning or thickening in knees with, or at risk of, osteoarthritis (OA) and examine their association with clinical and radiographic covariates. Design: Knee cartilage thickness change over 12 months was measured using magnetic resonance imaging in the right knee of 757 Osteoarthritis Initiative (OAI) participants that had radiographic findings of osteophytes or joint space narrowing (JSN). Thickness changes in individual knees were classified as having rapid thinning or thickening or no detectable OA-related change when compared to asymptomatic OAI Control cohort knees. Results: Cartilage thinning, found in 18.5% of subjects, was more frequent in knees with OAI calculated Kellgren-Lawrence grade (cKLG) > 2 (P < 0.001) and with frequent pain (P = 0.047). No link was found between body mass index, sex, and age and cartilage thinning (P > 0.15). The percent of knees with thickening was small (4.4%), but greater in knees with frequent pain (P = 0.02). Rapid thinning was most common in the central (36.4%) and external (32.1%) subregions of the medial weight-bearing femur. Mean cartilage loss in rapidly thinning subregions ranged from 11.2%/y to 24.6%/y. Knees with cKLG > 2, but classified as having no detectable OA-related change had mean cartilage loss rates significantly >0 (0.4%/y-1.3%/y) in 10 subregions. Conclusion: Most observed subregional changes in OA knees were indistinguishable from changes found in an asymptomatic cohort, but a fraction of subregions showed rapid progression. The relative frequency of rapid thinning increases when cKLG > 2, a classification closely associated with JSN and/or frequent knee pain are present. © 2012 Osteoarthritis Research Society International.


Ruhdorfer A.,Paracelsus Medical University | Wirth W.,Paracelsus Medical University | Wirth W.,Chondrometrics GmbH | Hitzl W.,Paracelsus Medical University | And 3 more authors.
Arthritis Care and Research | Year: 2014

Objective. To determine whether thigh muscle strength differs between symptomatic and asymptomatic knees, and/or different radiographic strata of knee osteoarthritis (KOA). Methods. Isometric extensor and flexor strength were analyzed in 3,809 Osteoarthritis Initiative participants (2,201 women and 1,608 men) with central radiographic Kellgren/Lawrence (K/L) grade readings. Isometric strength measurements were stratified by radiographic disease status (K/L grades 0, 1, 2, and 3/4) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain scores. Age-adjusted, separate-slopes analysis of covariance models was used to compare strength between " symptomatic" (WOMAC score range 5-20) and "asymptomatic" (WOMAC score = 0) legs within and across K/L grade strata. Exploratory analyses focused on strength normalized to body weight and symptom frequency. Results. Isometric strength was significantly lower in symptomatic than in asymptomatic legs: -11 to -13% for extensor strength and -7 to -16% for flexor strength (P < 0.0001 for both) in men, and -9 to -17% (P = 0.029) for extensor strength, and -10 to -21% (P = 0.049) for flexor strength in women. Similar observations were made for pain frequency strata. Extensor and flexor strength were not significantly different across K/L grade strata in asymptomatic legs in either sex (P ≥ 0.12). However, strength normalized to body weight was lower at higher K/L grades in both sexes (P ≤ 0.02) because the body mass index was greater in participants with more advanced radiographic disease. Conclusion. Knee symptoms (i.e., pain) appear to be the relevant determinant of isometric knee extensor and flexor strength in KOA, whereas no direct association between strength and radiographic severity was observed. These findings suggest that the reduction in thigh muscle strength in KOA is related to pain but not to the structural (radiographic) disease status. Copyright © 2014 by the American College of Rheumatology.


Eckstein F.,Paracelsus Medical University | Eckstein F.,Chondrometrics GmbH | Kwoh C.K.,University of Arizona | Link T.M.,University of California at San Francisco
Annals of the Rheumatic Diseases | Year: 2014

The Osteoarthritis Initiative (OAI) is a multicentre, prospective, observational, cohort study of knee osteoarthritis (OA) that began recruitment in 2004. The OAI provides public access to clinical and image data, enabling researchers to examine risk factors/predictors and the natural history of knee OA incidence and progression, and the qualification of imaging and other biomarkers. In this narrative review, we report imaging findings and lessons learned 10 years after enrolment has started. A literature search for full text articles published from the OAI was performed up to 31 December 2013 using Pubmed and the OAI web page. We summarise the rationale, design and imaging protocol of the OAI, and the history of OAI publications. We review studies from early partial, and later full OAI public data releases. The latter are structured by imaging method and tissue, reviewing radiography and then MRI findings on cartilage morphology, cartilage lesions and composition (T2), bone, meniscus, muscle and adipose tissue. Finally, analyses directly comparing findings from MRI and radiography are summarised. Ten years after the first participants were enrolled and first papers published, the OAI has become an invaluable resource to the OA research community. It has fuelled novel methodological approaches of analysing images, and has provided a wealth of information on OA pathophysiology. Continued collection and public release of long-term observations will help imaging measures to gain scientific and regulatory acceptance as 'prognostic' or 'efficacy of intervention' biomarkers, potentially enabling shorter and more efficient clinical trials that can test structure-modifying therapeutic interventions (NCT00080171).


Eckstein F.,Paracelsus Medical University | Wirth W.,Chondrometrics GmbH | Nevitt M.C.,University of California at San Francisco
Nature Reviews Rheumatology | Year: 2012

Osteoarthritis (OA) is the most common joint disorder.The Osteoarthritis Initiative (OAI) is a multicentre, longitudinal, prospective observational cohort study of knee OA that aims to provide publicly accessible clinical datasets, images and biospecimens, to enable researchers to investigate factors that influence the onset and development of OA, and evaluate biomarkers that predict and track the course of the disease.In this Perspectives, we describe the rationale and design of the OAI and its cohort, discuss imaging protocols and summarize image analyses completed to date.We include descriptive analyses of publicly available longitudinal (2-year) data of changes in cartilage thickness in a core sample of 600 knees from 590 participants in the OAI progression subcohort.Furthermore, we describe published methodological and applied imaging research that has emerged from OAI pilot studies and OAI data releases, and how these studies might contribute to clinical development of biomarkers for assessing the efficacy of intervention trials.© 2012 Macmillan Publishers Limited.All rights reserved .


Lohmander L.S.,Lund University | Lohmander L.S.,University of Southern Denmark | Hellot S.,Merck Serono | Dreher D.,Totzke and Dreher Scientific | And 5 more authors.
Arthritis and Rheumatology | Year: 2014

Objective To evaluate the efficacy and safety of intraarticular sprifermin (recombinant human fibroblast growth factor 18) in the treatment of symptomatic knee osteoarthritis (OA). Methods The study was a randomized, double-blind, placebo-controlled, proof-of-concept trial. Intraarticular sprifermin was evaluated at doses of 10 μg, 30 μg, and 100 μg. The primary efficacy end point was change in central medial femorotibial compartment cartilage thickness at 6 months and 12 months as determined using quantitative magnetic resonance imaging (qMRI). The primary safety end points were nature, incidence, and severity of local and systemic treatment-emergent adverse events (AEs) and acute inflammatory reactions, as well as results of laboratory assessments. Secondary end points included changes in total and compartment femorotibial cartilage thickness and volume as assessed by qMRI, changes in joint space width (JSW) seen on radiographs, and pain scores on the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Results One hundred ninety-two patients were randomized and evaluated for safety, 180 completed the trial, and 168 were evaluated for the primary efficacy end point. We found no statistically significant dose response in change in central medial femorotibial compartment cartilage thickness. Sprifermin was associated with statistically significant, dose-dependent reductions in loss of total and lateral femorotibial cartilage thickness and volume and in JSW narrowing in the lateral femorotibial compartment. All groups had improved WOMAC pain scores, with statistically significantly less improvement at 12 months in patients receiving the 100-μg dose of sprifermin as compared with those receiving placebo. There was no significant difference in serious AEs, treatment-emergent AEs, or acute inflammatory reactions between sprifermin and placebo groups. Conclusion No statistically significant relationship between treatment group and reduction in central medial femorotibial compartment cartilage thickness was observed; however, prespecified structural secondary end points showed statistically significant dose-dependent reductions after sprifermin treatment. Sprifermin was not associated with any local or systemic safety concerns. Copyright © 2014 by the American College of Rheumatology.


Eckstein F.,Paracelsus Medical University | Cotofana S.,Paracelsus Medical University | Wirth W.,Paracelsus Medical University | Nevitt M.,University of California at San Francisco | And 4 more authors.
Arthritis and Rheumatism | Year: 2011

Objective To investigate whether rates of cartilage loss differ in knees with frequent baseline pain versus those without pain, after adjustment for radiographic osteoarthritis (OA) stage. Methods One knee in each of 718 Osteoarthritis Initiative participants was examined: 310 with calculated Kellgren/Lawrence (K/L) grade 2, 299 with calculated K/L grade 3, and 109 with calculated K/L grade 4. Twelve-month change in (subregional) cartilage thickness was assessed by magnetic resonance imaging. Change in cartilage thickness in the central subregion of the weight-bearing medial femoral condyle and ordered value 1 (OV1) were selected as primary end points. Frequent knee symptoms were defined as pain, aching, or stiffness on most days of at least 1 month during the previous year. Results The mean 12-month rate of change in cartilage thickness in the central subregion of the medial femoral condyle was -12 μm (standardized response mean [SRM] -0.15) in knees without pain (n = 146), -27 μm (SRM -0.25) in those with infrequent pain (n = 255), and -54 μm (SRM -0.32) in those with frequent pain (n = 317). Rates differed significantly between frequently painful knees and pain-free knees after adjustment for age, sex, body mass index, and calculated K/L grade (P = 0.011, R2 = 2.6%, partial R2 for frequent pain = 1.4%). Similar results were found in stratified samples of calculated K/L grade 2/calculated K/L grade 3 knees, and in analyses restricted to knees with consistent pain frequency between baseline and followup. OV1 results showed similar trends but were not significant. Conclusion Knees with frequent pain display greater rates of medial cartilage loss longitudinally than knees without pain, with or without adjustment or stratification for radiographic disease stage. Enrollment of participants with frequent knee pain in clinical trials can increase the observed rate of structural progression (i.e., cartilage loss) and sensitivity to change. Copyright © 2011 by the American College of Rheumatology.


Crema M.D.,University of Massachusetts Boston | Crema M.D.,University of Sydney | Crema M.D.,Beth Israel Deaconess Medical Center | Crema M.D.,Chondrometrics GmbH
Annals of the rheumatic diseases | Year: 2014

OBJECTIVE: To determine the association between changes in the delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) index over 2 years as a measure of cartilage proteoglycan concentration, with changes in cartilage thickness in the medial tibiofemoral compartment of knees in middle-aged women.METHODS: One hundred and forty-eight women (one knee for each subject) aged ≥40 years were included. 3.0 T MR images of the knee were acquired at baseline, 1 year and 2 years. Three-dimensional (3D) spoiled gradient recalled echo (SPGR) sequences (for cartilage thickness) and 3D inversion recovery-prepared SPGR sequences after dGEMRIC were acquired. Segmentation was performed in the medial central (weight-bearing) femur and tibia to determine cartilage proteoglycan concentration and thickness. The association of change in the dGEMRIC indices between baseline and 1-year follow-up with (a) concomitant changes in cartilage thickness and (b) change in cartilage thickness between 1 and 2 years was assessed using linear regression.RESULTS: In the whole-sample model, a decrease in dGEMRIC indices over time at the central medial femur significantly predicted an increase in cartilage thickness at both the central medial femur (p=0.008) and the medial tibia (p=0.04).CONCLUSIONS: A decrease in dGEMRIC indices was associated with an increase in cartilage thickness in the medial compartment. Our results suggest that an increase in cartilage thickness may also be related to a decrease in proteoglycan concentration, which may represent swelling of cartilage in early stages of degeneration. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.


Eckstein F.,Paracelsus Medical University | Eckstein F.,Chondrometrics GmbH | Le Graverand M.-P.H.,Pfizer
Seminars in Arthritis and Rheumatism | Year: 2015

Osteoarthritis (OA) is the most common disease of synovial joints and currently lacks treatment options that modify structural pathology. Imaging is ideally suited for directly evaluating efficacy of disease-modifying OA drugs (DMOADs) in clinical trials, with plain radiography and MRI being most often applied. The current article is based on a debate held on April 26, 2014, at the World Congress of Osteoarthritis: The authors were invited to contrast strengths and limitations of both methods, highlighting scientific evidence on reliability, construct-validity, and correlations with clinical outcome, and comparing their sensitivity to change in knee OA and sensitivity to DMOAD treatment. The authors concluded that MRI provides more comprehensive information on articular tissues pathology, and that implementation of radiography in clinical trials remains a challenge. However, neither technique has thus far been demonstrated to be strongly superior over the other; for the time being it therefore appears advisable to use both in parallel in clinical trials, to provide more evidence on their relative performance. Radiographic JSW strongly depends on adequate positioning; it is not specific to cartilage loss but also to the meniscus. MRI provides somewhat superior sensitivity to change compared with the commonly used non-fluoroscopic radiographic acquisition protocols, and has recently provided non-location-dependent measures of cartilage thickness loss and gain, which are potentially more sensitive in detecting DMOAD effects than radiographic JSW or region-specific MRI. Non-location-dependent measures of cartilage thickness change should thus be explored further in context of anabolic and anti-catabolic DMOADs. © 2015 Elsevier Inc.


Eckstein F.,Paracelsus Medical University | Eckstein F.,Chondrometrics GmbH | Wirth W.,Paracelsus Medical University | Lohmander L.S.,Lund University | And 3 more authors.
Arthritis and Rheumatology | Year: 2015

Objective Anterior cruciate ligament (ACL) rupture involves an increased risk of osteoarthritis. The purpose of this study was to explore changes in cartilage thickness over 5 years after ACL rupture.Methods A total of 121 young active adults (ages 18-35 years; 26% women) from the Knee ACL, Nonsurgical versus Surgical Treatment (KANON) study, who had acute traumatic rupture of the ACL were studied. Sagittal magnetic resonance images were acquired within 4 weeks of ACL rupture (baseline) and at the 2-year and 5-year followup assessments. Medial and lateral femorotibial cartilage was segmented (with blinding to acquisition order), and the mean cartilage thickness was computed across 16 femorotibial subregions. Total femorotibial cartilage thickness change was the primary analytic focus. Maximal subregional mean cartilage thickness loss (ordered value 1 [OV1]) and gain (ordered value 16 [OV16]), independent of its specific location in individual knees, were the secondary analytic focus.Results Overall femorotibial cartilage thickness increased by 31 μm/year over 5 years (95% confidence interval 18, 44). The increase was similar in men and women and was significantly greater in those younger, as compared with those older, than the median age (25.3 years). The rate of total cartilage thickness change did not differ significantly between the first 2 years and the later 3 years. However, the maximal annualized subregional cartilage loss (OV1) and gain (OV16) were both significantly greater (P < 0.001 and P < 0.05, respectively) during the earlier interval than during the later interval (-115 versus -54 μm [OV1] and 116 versus 69 μm [OV16]) .Conclusion Cartilage thickening was observed over 5 years following ACL injury, particularly in the medial femorotibial compartment and in younger subjects. Major perturbations in cartilage homeostasis were seen over the first 2 years after ACL rupture, with simultaneous subregional thinning and thickening occurring within the same cartilage plate or compartment. © 2015 The Authors. Arthritis & Rheumatology is published by Wiley Periodicals, Inc.

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