ObjectiveTo investigate host and gut-microbiota related Tryptophan metabolism in hand osteoarthritis (HOA).MethodsThe baseline serum concentration of 20 Tryptophan metabolites was measured in 416... Show moreObjectiveTo investigate host and gut-microbiota related Tryptophan metabolism in hand osteoarthritis (HOA).MethodsThe baseline serum concentration of 20 Tryptophan metabolites was measured in 416 HOA patients in a cross-sectional analysis of the DIGICOD cohort. Tryptophan metabolites levels, metabolite-ratios and metabolism pathway activation were compared between erosive (N = 141) and non-erosive HOA (N = 275) by multiple logistic regressions adjusted on age, BMI and sex. The association between Tryptophan metabolite levels and HOA symptoms was investigated by a Spearman's rank correlation analysis.ResultsFour serum Tryptophan metabolites, eight metabolite ratios and one metabolism pathway were associated with erosive HOA. Erosive HOA was negatively associated with Tryptophan (odds ratio (OR) = 0.41, 95% confidence interval [0.24–0.70]), indole-3-aldehyde (OR = 0.67 [0.51–0.90]) and 3-OH-anthranilic acid (OR = 1.32 [1.13–1.54]) and positively with 5-OH-Tryptophan levels (OR = 1.41 [1.13–1.77]). The pro-inflammatory kynurenine–indoleamine 2,3-dioxygenase pathway was upregulated in erosive HOA (OR = 1.60 [1.11–2.29]). Eleven metabolites were correlated with HOA symptoms and were mostly pain-related. Serotonin and N-acetyl serotonin levels were negatively correlated with number of tender joints. Indole-3-aldehyde level was negatively correlated and 3-OH-anthranilic acid, 3-OH-kynurenine and 5-OH-Tryptophan levels were positively correlated with number of patients-reported painful joints. Quinolinic acid and 3-OH-kynurenine levels correlated positively with AUSCAN pain.ConclusionsTryptophan metabolites disturbance is associated with erosive HOA and pain and emphasize the role of low-grade inflammation and gut dysbiosis in HOA. Show less
Background: Hand osteoarthritis (HOA) is a highly prevalent rheumatic disease that predominates in females and causes pain and loss of functional capacity. Obesity and metabolic syndrome have been... Show moreBackground: Hand osteoarthritis (HOA) is a highly prevalent rheumatic disease that predominates in females and causes pain and loss of functional capacity. Obesity and metabolic syndrome have been previously suggested to associate with the severity of HOA, but clarity on these associations is yet to be achieved.Objective: Test the association between obesity and other components of the metabolic syndrome and disability in women with hand osteoarthritis (HOA).Design: Individuals from EpiReumaPt epidemiological community-based study (2011-2013) are representative of the Portuguese population. Women with diagnosis of primary HOA were included.Primary outcome: hand functional status, assessed by Cochin questionnaire.Secondary outcomes: hand pain, assessed by visual analogue scale and tender hand joint count (THJ).Explanatory variables: obesity, diabetes mellitus, arterial hypertension and hypercholesterolemia. Possible associations between obesity and the other components of metabolic syndrome with Cochin score, hand pain and THJ were tested in a multivariable linear regression model.Potential confounders considered: age, education level and countrywide distribution.Results: 473 women with primary HOA were included. Forty percent were overweight and 29% obese. Ninety-three (19.8%) participants had diabetes, 261 (55.8%) reported hypertension and 261 (55.9%) hypercholesterolemia. Mean Cochin score was 15.5 +/- 14.8, mean pain VAS was 4.7 +/- 2.6 and mean THJ 1.4 +/- 3. In the multivariable analysis, obesity (beta 4.6 CI 0.7;8.5) and diabetes (beta 4.0 CI 0.4;7.6) were found to significantly associate with HOA functional disability. In addition, diabetes, but not obesity, associated with hand pain. There was no association between obesity or diabetes with THJ.Conclusion: In a Portuguese female population with primary HOA, obesity and diabetes mellitus independently associated with a worse hand functional status. These data add to evidence suggesting a role of metabolic factors in the severity of HOA. Show less
This thesis describes research done in the field of hand osteoarthritis, and had the following three aims:1) To evaluate the current state of treatment options in hand osteoarthritis;2) To... Show moreThis thesis describes research done in the field of hand osteoarthritis, and had the following three aims:1) To evaluate the current state of treatment options in hand osteoarthritis;2) To investigate the role of inflammation as a treatment target in hand osteoarthritis; and3) To facilitate development of new treatment options by improving outcome measurement in hand osteoarthritis. Show less
Kroon, F.P.B.; Beest, S. van; Ermurat, S.; Kortekaas, M.C.; Bloem, J.L.; Reijnierse, M.; ... ; Kloppenburg, M. 2018
Conclusions: Assessment of progression in hand OA defined by JSW measurements is possible, but performs less well than progression defined by JSN scoring. Therefore, the value of JSW measurements... Show moreConclusions: Assessment of progression in hand OA defined by JSW measurements is possible, but performs less well than progression defined by JSN scoring. Therefore, the value of JSW measurements in hand OA clinical trials remains questionable. (C) 2016 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved. Show less
Kloppenburg, M.; Maheu, E.; Kraus, V.B.; Cicuttini, F.M.; Doherty, M.; Dreiser, R.L.; ... ; OARSI Hand Clinical Trial Recommen 2015
This thesis focuses on epidemiological studies of hand OA in secondary care, erosive OA as a subset of hand OA and the added value of imaging in hand OA to understand better the pathophysiology of... Show moreThis thesis focuses on epidemiological studies of hand OA in secondary care, erosive OA as a subset of hand OA and the added value of imaging in hand OA to understand better the pathophysiology of hand OA and seek for opportunities to define progression in an earlier stage. Chapter 2 gives an overview about the current knowledge on hand OA and it is clear that hand OA is a prevalent, heterogeneous disorder (including several hand OA subsets) that can cause considerable pain and disability. Much less is known about the risk factors of progression in hand OA. Moderate evidence for an abnormal scintigram at baseline was found as a risk factor for radiographic progression in a systematic review as described in chapter 3. In rheumatology practice, the most prevalent phenotype of OA is hand OA as depicted in chapter 4. This symptomatic population experience a substantial lower health-related quality of life compared to the general population. The collaborations with the Rotterdam Study and NorStOP Study (chapter 5, 6, 7) revealed that 2.8% of the general population rising to 10.2% in the symptomatic population is affected by erosive disease in the interphalangeal joints (IPJs). Furthermore, erosions are not present in IPJs only and prevalence of erosive disease in 1st carpometacarpal joints (CMCJs) is also given. Persons with erosive OA in the interphalangeal joints report more pain and functional limitations, however to a lesser extent than persons with other rheumatic inflammatory diseases. Inflammation does play a role in OA joints with erosions, as assessed with Power Doppler Signal, greyscale synovitis and effusion on ultrasound (chapter 8). Also in OA joints without erosions, inflammatory signs are visible on ultrasound (chapter 9). Regarding other imaging modalities used in hand OA research, quantitative joint space width (JSW) measurements in hand OA joints have been shown to be associated with self-reported pain, functional ability and structural abnormalities (chapter 10), whereas features on Magnetic Resonance Imaging (MRI, such as abnormal collateral ligaments and bone marrow lesions) are also associated with pain upon palpation in individual joints (chapter 11). Finally, the health-related quality of life in hand OA patients in rheumatology practice can be improved with a protocol-led consultation about increasing the use of helping aids and acetaminophen given by a clinical nurse specialist (chapter 12). Show less
Obesity is a major risk factor of osteoarthritis development and progression. Theoretically, obesity is a factor that can be modified. While obesity epidemic is difficult to reverse because we live... Show moreObesity is a major risk factor of osteoarthritis development and progression. Theoretically, obesity is a factor that can be modified. While obesity epidemic is difficult to reverse because we live in lipogenic environment, personal approach in modify obesity may avail. Therefore, understanding how obesity leads to osteoarthritis is needed. The first three chapters of this thesis investigate several aspects of osteoarthritis: what structures are damaged, what factors are associated with worsening of osteoarthritis and how to measure worsening of osteoarthritis. The other four chapters investigate the link between obesity and osteoarthritis. We show that obesity is associated with hand osteoarthritis. Since we do not walk on our hand, there must be another factor than mechanical that cause joint damage in osteoarthritis. One of the factors is adipokines, protein produced mainly by fat tissue. We showed that adiponectin, one of the adipokines, prevents worsening of hand osteoarthritis. We concluded that obesity plays role in osteoarthritis not only due to added mechanical force but also due to added metabolic force (adipokines). These adipokines might be used as target in modifying the effect of obesity on osteoarthritis. However, we still need more studies on how obesity links with osteoarthritis Show less
