Identification of serological biomarker profiles associated with total joint replacement in osteoarthritis patients

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The aim of this narrative review is to summarize important findings from biochemical marker studies relevant to osteoarthritis (OA) in the context of new discoveries and clinical and scientific need. Design: We conducted a systematic search of electronic medical databases (Embase, Medline, Web of Science, Cochrane central) between 01-03-2017 and 31-03-2018. The search was restricted to human studies, English language and full text available publications while reviews were excluded. Only papers describing protein based biomarkers measured in human body fluids (blood, urine and synovial fluid (SF)) were included. Of the 992 papers, 86 were reviewed here, with inclusion primarily based on relevance to OA biochemical markers. Results: This review highlights a selection of studies based on their quality and perceived importance to the field mainly including those that 1 evaluate prognostic value of biomarkers for OA progression (i.e., biomarkers reflecting change in composition of joint tissues and biomarkers of inflammation) 2 , help in assessment of intervention efficacy, and 3 are innovative and uncover new candidate biomarkers, or use new approaches in biomarker discovery. Conclusions: Key findings and implications for possible clinical utility of biochemical markers are summarized and discussed. Given the paucity of robust biomarkers within the field, and the heterogeneity of the condition, enormous works are needed for development and validation of novel and clinically applicable biomarkers to reduce the impact of this highly prevalent and debilitating condition.

Section: Discussionmentioning

confidence: 99%

Section: Early and Late Assessment Of Intervention Efficacy And Undermentioning

confidence: 99%

Osteoarthritis year in review 2018: biomarkers (biochemical markers)

Hosnijeh

Bierma-Zeinstra

Bay‐Jensen

2019

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“…Classification and Regression Tree (CART) 11,12 methods that were used in the previous work 7 were also applied to develop multivariable predictive models in this subset of cases and controls. Models were fit including baseline, antecedent or coincident biomarker data for the limited or chronic NSAID users during tanezumab treatment.…”

Section: Discussionmentioning

confidence: 99%

“…variables as possible from the following list, as previously described 7 and Patient Global Assessment score of "poor" or "very poor; " otherwise, OA was classified as "not severe". In addition, controls were matched to the RPOA type-2 cases on NSAID use (<90 days or >90 days).…”

Section: Studies and Samplesmentioning

confidence: 99%

“…Given the large number of biomarker determinations per sample, we limited the number of matches to 2 which greatly improved the precision of estimates relative to single matching control and a pragmatic balance between statistical power and cost. For the data analysis, for the RPOA type-2 cases, the retention samples were binned according to the collection time relative to the timing of the RPOA type-2 event: baseline, antecedent (>3 months prior to the RPOA type-2 event) and coincident (within 3 months before the RPOA type-2 event) 10 . Post-dose control samples to match the cases had to be collected 21e182 days postdose for the antecedent analysis and >183 days postdose for the coincidence analysis.…”

Section: Studies and Samplesmentioning

confidence: 99%

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Serological biomarker profiles of rapidly progressive osteoarthritis in tanezumab-treated patients

Karsdal

Verburg

West

et al. 2019

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There is a need for efficacious and safe pain treatments for OA (osteoarthritis). The nerve growth factor (NGF) antibody tanezumab is associated with high efficacy, but when combined with chronic NSAID treatment shows an increased risk of rapidly progressive osteoarthritis (RPOA) in a small group of patients. Aim: The aim of this study was to phenotype with biochemical biomarkers of bone, cartilage, soft tissue, synovial metabolism OA patients who are at risk of developing RPOA type-2, for both limited and chronic NSAIDs users. Material and methods: The dataset consisted of OA patients participating in tanezumab trials who used NSAIDs <90 days (limited NSAID users) or chronic users (NSAIDs !90 days) over an average 10 month period. Biomarker data were available for 47 cases (RPOA type-2) and 92 controls. Non-linear and linear multivariable predictive models were developed. Results: By use of two biomarkers at baseline the receiver operating characteristic (ROC) curve area for RPOA type-2 in limited NSAID users was 71%, [CI] (60e83%). OA subjects with this biomarker phenotype had 8-fold higher confidence interval [CI][(2e33)] relative risk of developing RPOA type-2 as compared to OA patients without this phenotype. The AUC of the model in chronic NSAIDs users based on 5 biomarkers was 78%, [CI](69e88%), with 4-fold [CI (2e6)] relative risk of developing RPOA type-2. Conclusion: In this hypothesis generating and exploratory study, we identified combinations of biomarkers associated with OA patients who develop RPOA type-2, which may be related to the pathology of the RPOA type-2 joint.

Osteoarthritis biomarkers: year in review

Watt

2018

Discovery, characterisation and qualification of various biomarkers is ongoing; several novel protein and non-protein candidate biomarkers have been reported this year. Biomarkers provide us with an opportunity to better diagnose and stratify the disease, via established panels or new discovery approaches. Improving quality of sampling and testing, and measuring large numbers of markers simultaneously in large cohorts would seem likely to identify new clinically applicable biomarkers, which are still much needed in this disease.