The role of radiography and MRI for eligibility assessment in DMOAD trials of knee OA

Roemer, Frank W.; Kwoh, C. Kent; Hayashi, Daichi; Felson, David T.; Guermazi, Ali

doi:10.1038/s41584-018-0010-z

Cited by 67 publications

(60 citation statements)

References 77 publications

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“…Regulators have not yet approved any pharmacological therapies with convincing disease-improving effects. [ 21 , 22 ] Therefore, it is quite necessary to develop new, appropriate and effective therapies that can relieve, suspend, or even reverse the occurrence and progression of OA.…”

Section: Discussionmentioning

confidence: 99%

Identification of genes and pathways associated with subchondral bone in osteoarthritis via bioinformatic analysis

Yang

Kuang

et al. 2020

Medicine

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Osteoarthritis (OA) is a high prevalent musculoskeletal problem, which can cause severe pain, constitute a huge social and economic burden, and seriously damage the quality of life. This study was intended to identify genetic characteristics of subchondral bone in patients with OA and to elucidate the potential molecular mechanisms involved. Data of gene expression profiles (GSE51588), which contained 40 OA samples and 10 normal samples, was obtained from the Gene Expression Omnibus (GEO). The raw data were integrated to obtain differentially expressed genes (DEGs) and were further analyzed with bioinformatic analysis. The protein–protein interaction (PPI) networks were built and analyzed via Search Tool for the Retrieval of Interacting Genes (STRING). The significant modules and hub genes were identified via Cytoscape. Moreover, Gene Ontology (GO) and Kyoto Encyclopaedia of Genes and Genomes (KEGG) enrichment analysis were performed. Totally 235 DEGs were differentially expressed in the subchondral bone from OA patients compared with those of normal individuals, of which 78 were upregulated and 157 were downregulated. Eight hub genes were identified, including DEFA4, ARG1, LTF, RETN, PGLYRP1, OLFM4, ORM1, and BPI. The enrichment analyses of the DEGs and significant modules indicated that DEGs were mainly involved in inflammatory response, extracellular space, RAGE receptor binding, and amoebiasis pathway. The present study provides a novel and in-depth understanding of pathogenesis of the OA subchondral bone at molecular level. DEFA4, ARG1, LTF, RETN, PGLYRP1, OLFM4, ORM1, and BPI may be the new candidate targets for diagnosis and therapies on patients with OA in the future.

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Section: Discussionmentioning

confidence: 99%

Identification of genes and pathways associated with subchondral bone in osteoarthritis via bioinformatic analysis

Yang

Kuang

et al. 2020

Medicine

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“…OA is a disease process involving multiple joint tissues including those not visible on radiography [1], and is a complex disease process with multiple phenotypes [2,3] that require evaluation by multimodality imaging assessment. Therefore, the use of more advanced imaging modalities such as magnetic resonance imaging (MRI) has become important in OA research [1,4]. For imaging of OA, MRI plays a major role in the research setting, with compositional MRI techniques becoming increasingly more important due to their capacity to assess 'pre-morphologic' biochemical compositional changes of articular and periarticular tissues [5].…”

Section: Introductionmentioning

confidence: 99%

A 24-Month Follow-Up Study of the Effect of Intra-Articular Injection of Autologous Microfragmented Fat Tissue on Proteoglycan Synthesis in Patients with Knee Osteoarthritis

Borić

Hudetz

Rod

et al. 2019

Genes

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Osteoarthritis (OA) is a widely prevalent disease worldwide, and with an increasingly ageing society, it has become a challenge for the field of regenerative medicine. OA is a disease process involving multiple joint tissues, including those not visible on radiography, and is a complex disease process with multiple phenotypes that require evaluation by a multimodality imaging assessment. The purpose of this study was to evaluate the effect of micro-fragmented fat tissue intra-articular injection 24 months after application in two ways: Indirectly using functional magnetic resonance imaging (MRI) assessment analyzing the glycosaminoglycans (GAG) content in cartilage by means of delayed gadolinium (Gd)-enhanced magnetic resonance imaging of cartilage (dGEMRIC), as well as clinical outcome on observed level of GAG using standard orthopedic physical examination including VAS assessment. In our previous study assessing comprehensive results after 12 months, the dGEMRIC results have drawn attention. The present study explores the long-term effect of intra-articular injection of autologous microfragmented adipose tissue to host chondrocytes and cartilage proteoglycans in patients with knee OA. A prospective, non-randomized, interventional, single-center, open-label clinical trial was conducted from January 2016 to April 2018. A total of 17 patients were enrolled in the study, and 32 knees were assessed in a 12-month follow-up, but only 10 patients of them with 18 knees are included in a 24-month follow-up. The rest of the seven patients dropped out of the study 12 months after follow-up: three patients underwent knee arthroplasty, and the remaining four did not fulfil the basic criteria of 24 months involvement in the study. Surgical intervention (lipoaspiration), followed by tissue processing and intra-articular injection of the final microfragmented adipose tissue product into the affected knee(s), was performed in all patients. Patients were assessed for a visual analog scale (VAS), dGEMRIC at the baseline, three, six, 12 and 24 months after the treatment. A magnetic resonance sequence in dGEMRIC due to infiltration of the anionic, negatively-charged contrast gadopentetate dimeglumine (Gd-DTPA2) into the cartilage indicated that the contents of cartilage glycosaminoglycans significantly increased in specific areas of the treated knee joint. Our results suggest that this method of single intra-articular injection of autologous microfragmented adipose tissue improves GAG content on a significant scale, with over half of the measurements suggesting relevant improvement 24 months after intra-articular injection opposed to the expected GAG decrease over the natural course of the disease.

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“…Reasons for failure of DMOAD trials in recent years are complex but include X-ray based eligibility screening 6,14,16 . X-ray is only able to depict osseous changes and is not able to show OA-related tissue changes other than osteophytes, joint space narrowing, sclerosis, cysts and attrition -features that are commonly not considered treatment targets.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, several entities have come into focus in recent years that are perceived to be potentially detrimental to the joint, are a reflection of systemic disease such as malignancy or are considered risk factors for rapid disease progression or joint collapse and thus, considered exclusionary in clinical DMOAD or symptom-relieving trials 14 . While in general these entities are considered uncommon, none of these are detectable by radiography or only at late stages.…”

Section: Introductionmentioning

confidence: 99%

MRI-based screening for structural definition of eligibility in clinical DMOAD trials: Rapid OsteoArthritis MRI Eligibility Score (ROAMES)

Roemer

Collins

Kwoh

et al. 2020

Osteoarthritis and Cartilage

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Purpose: Our aim was to introduce a simplified MRI instrument, Rapid OsteoArthritis MRI Eligibility Score (ROAMES), for defining structural eligibility of patients for inclusion in disease-modifying osteoarthritis drug trials using a tri-compartmental anatomic approach that enables stratification of knees into different structural phenotypes and includes diagnoses of exclusion. We also aimed to define overlap between phenotypes and determine reliability. Methods: 50 knees from the Foundation for National Institutes of Health Osteoarthritis Biomarkers study, a nested case-control study within the Osteoarthritis Initiative, were selected within pre-defined definitions of phenotypes as either inflammatory, subchondral bone, meniscus/cartilage, atrophic or hypertrophic. A focused scoring instrument was developed covering cartilage, meniscal damage, inflammation and osteophytes. Diagnoses of exclusion were meniscal root tears, osteonecrosis, subchondral insufficiency fracture, tumors, malignant marrow infiltration and acute traumatic changes. Reliability was determined using weighted kappa statistics. Descriptive statistics were used for determining concordance between the a priori phenotypic definition and ROAMES and overlap between phenotypes. Results: ROAMES identified 43 of 50 (86%) pre-defined phenotypes correctly. Of the 50 participants, 27 (54%) had no additional phenotypes other than the pre-defined phenotype. 18 (36%) had one and 5 (10%) had two additional phenotypes. None had three or four additional phenotypes. All features of ROAMES showed almost perfect agreement. One case with osteonecrosis and one with a tumor were detected. Conclusions: ROAMES is able to screen and stratify potentially eligible knees into different structural phenotypes and record relevant diagnoses of exclusion. Reliability of the instrument showed almost perfect agreement.

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The role of radiography and MRI for eligibility assessment in DMOAD trials of knee OA

Cited by 67 publications

References 77 publications

Identification of genes and pathways associated with subchondral bone in osteoarthritis via bioinformatic analysis

Identification of genes and pathways associated with subchondral bone in osteoarthritis via bioinformatic analysis

A 24-Month Follow-Up Study of the Effect of Intra-Articular Injection of Autologous Microfragmented Fat Tissue on Proteoglycan Synthesis in Patients with Knee Osteoarthritis

MRI-based screening for structural definition of eligibility in clinical DMOAD trials: Rapid OsteoArthritis MRI Eligibility Score (ROAMES)

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