Non-erosive Hand Osteoarthritis Research Articles

Serum tryptophan metabolites are associated with erosive hand osteoarthritis and pain: results from the DIGICOD cohort

To investigate host and gut-microbiota related Tryptophan metabolism in hand osteoarthritis (HOA). The 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. Four 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. Tryptophan metabolites disturbance is associated with erosive HOA and pain and emphasize the role of low-grade inflammation and gut dysbiosis in HOA.

Serum carboxymethyllysine concentration is associated with erosive hand osteoarthritis

Carboxymethyllysine (CML) and homocitrulline (HCit) are the products of two non-enzymatic post-translational modifications of protein, a process related to age. We investigated whether serum CML and HCit concentrations were associated with hand osteoarthritis (HOA), especially erosive HOA. Serum CML and HCit were measured by using liquid chromatography coupled with tandem mass spectrometry at inclusion in 386 patients included in the DIGItal Cohort Design (DIGICOD) cohort. We investigated whether serum CML and/or HCit concentrations were associated with erosive HOA or with HOA clinical and radiological features. Moreover, we compared the tissular concentrations of CML and HCit in OA and non-OA cartilage from proximal interphalangeal and metacarpo-phalangeal (MCP) joints from human cadaveric donors. Median (IQR) serum CML concentration was lower in patients with erosive HOA than those with non-erosive HOA (178.7 [157.1-208.8] vs 194.7 [168.9-217.1]μmol/mol Lys, P=0.002), but median HCit concentration did not differ between the groups (193.9 [162.9-232.0] vs 193.9 [155.9-224.6]μmol/mol Lys). Cartilage HCit and CML concentrations were not correlated with clinical features. Serum CML concentration was higher in OA than non-OA MCPs (7.0 vs 4.0mmol/mol Lys, P=0.01). Serum CML concentration was lower in erosive HOA than non-erosive HOA, and cartilage CML concentration was higher in OA than non-OA cartilage. These results encourage further studies to test whether serum CML could be a new prognostic biomarker in HOA.

Circulating miRNAs in hand osteoarthritis

Hand osteoarthritis (OA) is a frequent musculoskeletal disorder with an increasing prevalence during ageing. This study aimed to evaluate circulating microRNAs (miRNAs) in the plasma of patients with hand OA compared with age- and sex-matched healthy control subjects. In total, 238 participants (96 with erosive and 73 with non-erosive hand OA patients and 69 healthy control subjects) were included in this study. All patients underwent clinical examinations, including self-reported measures (AUSCAN and Algofunctional index). Radiographs of both hands were scored with the Kallman scale. The profile of miRNAs in plasma was screened using TaqMan™ Low-Density Array, and candidate miRNAs were validated on two quantitative real-time PCR (qRT-PCR) systems (QuantStudio and SmartChip). Of all the 754 miRNAs, 40 miRNAs were different between hand OA patients and healthy control subjects in the screening cohort. Following the two-phase validation process, three miRNAs (miR-23a-3p, miR-146a-5p, and miR-652-3p) were increased in patients with hand OA compared with healthy control subjects and were associated with the AUSCAN sum score and AUSCAN pain. Furthermore, an inverse correlation of miR-222-3p with the Kallman radiographic score was found. The expression of miRNAs did not differ between erosive and non-erosive hand OA. The profile of circulating miRNAs could unveil candidate biomarkers associated with hand OA symptoms. Longitudinal studies are required to determine the role of miRNAs in hand OA.

A two-year longitudinal study: Bone Loss in Patients with Erosive and Non-erosive Hand Osteoarthritis, Comparison

A two-year longitudinal study: Bone Loss in Patients with Erosive and Non-erosive Hand Osteoarthritis, Comparison

Erosive hand osteoarthritis: latest findings and outlook.

Osteoarthritis (OA) most commonly affects knee joints, and the next most commonly affected sites are the hands and hips. Three distinct hand OA phenotypes have been described: erosive hand OA (EHOA), nodal hand OA - also known as non-erosive hand OA (non-EHOA) - and first carpometacarpal joint OA. EHOA predominantly affects women and is the most aggressive form of hand OA, characterized by a severe clinical onset and progression, leading to joint damage, disability and reduction of quality of life. Clinical signs of inflammation associated with EHOA include the acute onset of pain, swelling and redness. Moreover, EHOA is characterized by radiographic features such as central erosion, saw-tooth and gull-wing lesions and, rarely, ankylosis. The aim of this Review is to report the latest findings on epidemiology, clinical features, pathology and aetiopathogenesis, biomarkers, imaging modalities and treatments for EHOA. The ongoing development of new hand OA classification criteria should facilitate standardization between studies.

A qualitative exploration of the patient experience of erosive and non-erosive hand osteoarthritis

BackgroundMany patients with hand osteoarthritis (HOA) experience reduced health-related quality of life. This study sought to better understand the disease and treatment experience of individuals with HOA, explore any differences in experiences between erosive and non-erosive HOA sub-types, and evaluate content validity of the Michigan Hand Outcomes Questionnaire (MHQ) in HOA.MethodsThirty subjects from the United States (n = 15 erosive HOA; n = 15 non-erosive HOA) participated in semi-structured interviews: concept elicitation explored symptoms/impacts important to patients; cognitive interviews assessed understanding and relevance of the MHQ. A sub-sample participated in real-time data capture (RTDC) activities via a smartphone/tablet app over 7 days. Verbatim transcripts were coded using Atlas.ti software and thematically analyzed. Concept saturation and MHQ content validity were evaluated.ResultsMost participants reported experiencing pain, swelling and stiffness, symptoms that most commonly had a direct impact on physical functioning. Substantial impacts on activities of daily living, emotional functioning, sleep and work were also reported. RTDC findings corroborated concept elicitation findings. There were no notable differences between erosive and non-erosive HOA, except nodules were reported more frequently in erosive disease. Most participants used analgesic treatments, but effects were short-lived. Pain was the symptom most frequently reported as most bothersome and important to treat. Concept saturation was achieved. MHQ items and instructions were well understood and relevant to most participants; stiffness and swelling were reported as important symptoms not included in the MHQ.ConclusionsThis study characterizes key symptoms of HOA which are burdensome for patients and not well controlled by current therapies, highlighting an unmet treatment need. Although the study is limited by a small sample size that may not be representative of the broader erosive and non-erosive HOA population, concept saturation was achieved, and our findings suggest that disease experience is similar for patients with erosive and non-erosive HOA. Evaluation of stiffness and swelling items in conjunction with the MHQ may enhance relevance and improve measurement precision to assess important domains of HQRoL in an HOA population.

Chemokine and Cytokine Profiles in Patients with Hand Osteoarthritis.

Background: The development of hand osteoarthritis (HOA) and its progression into the erosive subset are unclear, but inflammation is suspected to be the main source. To verify the involvement of inflammation in HOA pathogenesis, we evaluate serum inflammatory mediators and their association with HOA-related clinical features in patients. Methods: 153 participants (50 non-erosive HOA patients, 54 erosive HOA patients, and 49 healthy control subjects) were included in this study. All patients underwent clinical examination, which included assessment of tender and swollen small hand joints, ultrasound (US) examination, and self-reported measures (e.g., AUSCAN or algofunctional indexes). Serum inflammatory mediators were quantified using human cytokine 27-plex immunoassay. We employed linear modelling, correlation analysis, and resampling statistics to evaluate the association of these mediators to HOA. Results: We identified increased levels of nine inflammatory mediators (e.g., eotaxin, monocyte chemoattractant protein 1, interleukin-8, and tumour necrosis factor) in HOA patients compared to healthy controls. Increased mediators correlated with ultrasound findings as well as with clinically tender and swollen joint counts in patients with erosive HOA. However, none of the mediators distinguished between erosive and non-erosive HOA subtypes. Conclusion: Our findings support the hypothesis on the involvement of inflammation in HOA.

Hand strenght and dexterity in interphalangeal hand osteoarthritis and effects of osteophyte formations

BackgroundHand osteoarthritis (HOA) is a complex disorder with various subtypes characterized with predominance of different features. It is challenging to estimate the severity of hand disability in HOA, since contribution of different disease components to clinical burden is yet to be clarified. The aim of the study is to investigate hand functions in nonerosive interphalangeal hand osteoarthritis (HOA) without inflammatory features, and search for effects of osteophyte formations detected by radiography and ultrasound on functionality.MethodsThirty one HOA patients and 20 healthy subjects with similar age, gender, body mass index were included. Hand functions were evaluated by self-reported questionnaires and objective strength and dexterity measurements. A total of 459 interphalangeal joints were evaluated and scored by radiography and ultrasound for ostephyte formations.ResultsStrength and dexterity measurements were similar between groups. Self-reported functionality was hampered in HOA group but not statistically significant. Osteophyte scores obtained by ultrasound and radiography were significantly higher in HOA group. Osteophyte scores obtained by ultrasound were higher than the scores obtained by radiography. Ultrasound scores showed no correlation with any of the parameters while osteophytes scores obtained by radiography partially showed a significant negative correlation with assembly part of dexterity testing.ConclusionsNo significant difference observed in hand strength and dexterity in nonerosive interphalangeal HOA patients withouth signs of inflammation when compared to healthy subjects. Osteophyte formations prominent enough to be deteceted by radiography may have a negative effect on hand dexterity.

Impact of thumb osteoarthritis on pain, function, and quality of life: a comparative study between erosive and non-erosive hand osteoarthritis.

The study was aimed to compare the impact of thumb base osteoarthritis (TBOA) on pain, function, and quality of life in patients with erosive or non-erosive hand osteoarthritis (HOA). This observational retrospective study included 232 patients: 64 with erosive HOA (EHOA) and concomitant TBOA, 36 with isolated EHOA, 97 with non-erosive HOA (non-EHOA) and TBOA, and 35 with isolated non-EHOA. Hand pain by a visual analogue scale (VAS), Functional Index for Hand Osteoarthritis (FIHOA) score, Health Assessment Questionnaire (HAQ), the Medical Outcomes Study 36-Item Short Form (SF-36), and the possible correlations between VAS and FIHOA with radiological score were assessed. No differences were found between EHOA with TBOA and isolated EHOA in VAS and FIHOA scores; opposite, there was a significant difference in VAS (p < 0.01) and FIHOA (p < 0.001) between subjects with non-EHOA and TBOA and patients with only non-EHOA. VAS and FIHOA values resulted slightly higher in patients with EHOA and TBOA vs non-EHOA and TBOA; they were significantly more elevated in EHOA and TBOA group compared to isolated non-EHOA (p ≤ 0.001) and in isolated EHOA vs isolated non-EHOA (p < 0.01 and p < 0.001, respectively). HAQ, SF-36 resulted significantly better in isolated non-EHOA patients compared to the other groups. Finally, we observed a significant correlation between FIHOA and all the Kallman scales in EHOA patients with TBOA and between FIHOA and Kallman's thumb score in non-EHOA-TBOA group. EHOA has a more severe clinical burden than non-EHOA; the presence of TBOA appeared an important determinant of pain and disability in non-EHOA.Key Points• Each subset of HOA can have a different impact on pain and functionality, with EHOA determining more severe effects on hand symptoms and disability than non-EHOA.• The presence of TBOA appeared an important determinant of pain and disability in non-EHOA, but not in EHOA.• Our findings support the need for an individualized therapy for each phenotype of hand osteoarthritis.

Exploring the Involvement of NLRP3 and IL-1β in Osteoarthritis of the Hand: Results from a Pilot Study.

Hand osteoarthritis (HOA) includes different subsets; a particular and uncommon form is erosive HOA (EHOA). Interleukin- (IL-) 1β plays a crucial role in the pathogenesis of osteoarthritis (OA); it is synthesized as an inactive precursor which requires the intervention of a cytosolic multiprotein complex, named inflammasome, for its activation. The aim of this study was to investigate the involvement of IL-1β and the NOD-like receptor pyrin domain containing 3 (NLRP3) inflammasome in patients with EHOA and nonerosive HOA (NEHOA) compared to healthy controls. In particular, we evaluated the gene expression of IL-1β and NLRP3, the serum levels of IL-1β, IL-6, IL-17, and tumor necrosis factor- (TNF-) α, and the protein levels of IL-1β and NLRP3. We also assessed the relationships between IL-1β and NLRP3 and clinical, laboratory, and radiological findings. Fifty-four patients with HOA (25 EHOA and 29 NEHOA) and 20 healthy subjects were included in the study. Peripheral blood mononuclear cell (PBMC) gene and protein expressions of IL-1β and NLRP3 were quantified by quantitative real-time PCR and western blot. IL-1β, IL-6, IL-17, and TNF-α serum levels were determined by ELISA. IL-1β gene expression was significantly reduced (p = 0.0208) in EHOA compared to healthy controls. NLRP3 protein levels were significantly increased in the NEHOA group versus the control (p = 0.0063) and EHOA groups (p = 0.0038). IL-1β serum levels were not significantly different across the groups; IL-6, IL-17, and TNF-α were not detectable in any sample. IL-1β concentrations were negatively correlated with the Kellgren-Lawrence score in the whole population (r = −0.446; p = 0.0008) and in NEHOA (r = −0.608; p = 0.004), while IL-1β gene expression was positively correlated with the number of joint swellings in the EHOA group (r = 0.512; p = 0.011). Taken together, our results, showing poorly detectable IL-1β concentrations and minimal inflammasome activity in the PBMCs of HOA patients, suggest a low grade of systemic inflammation in HOA. This evidence does not preclude a possible involvement of these factors at the local level.

Presence of Autoantibodies in Erosive Hand Osteoarthritis and Association with Clinical Presentation.

To investigate whether 3 rheumatoid arthritis-associated antibodies [rheumatoid factor (RF) and anticitrullinated protein antibodies (ACPA) or anticarbamylated protein (anti-CarP) antibodies] are present in hand osteoarthritis (HOA) and associate with erosive OA (EOA). Anti-CarP IgG was measured by ELISA in baseline sera of patients with HOA from 3 cohorts: HOSTAS (n = 510, 27.2% EOA), ECHO (n = 47), and EHOA (n = 23), and in sera of healthy controls (HC; n = 196, mean age 44.1 yrs, 51.0% women). Moreover, ACPA-IgG and RF-IgM were additionally determined in HOSTAS and HC. The prevalence of autoantibodies was compared between HOA and HC and between erosive and nonerosive HOA. In HOSTAS, hand radiographs were scored (Kellgren-Lawrence, Osteoarthritis Research Society International osteophyte and joint space narrowing) and C-reactive protein (CRP) levels, representing inflammation, were assessed. Groups were compared using nonparametric tests. The prevalence of anti-CarP was low and not significantly different between the total HOA group and HC (6.6% vs 3.6%, p = 0.12). In HOSTAS, the prevalence of all tested autoantibodies was low (anti-CarP 7.1%, ACPA 0.8%, RF 6.1%), and there were no significant differences observed between HOA patients and HC or between erosive and nonerosive HOA. Further, radiographic damage and CRP levels were similar in anti-CarP+ and anti-CarP-, and RF+ and RF- HOSTAS patients. The prevalence of autoantibodies is similar in HOA patients and HC, and these autoantibodies are not associated with erosive disease, structural damage, or inflammation in patients with HOA, indicating that another mechanism is driving erosive disease.

Biomarkers of hand osteoarthritis.

Hand osteoarthritis (OA) is a common degenerative joint disorder leading to substantial pain and disability. The most severe subtype is erosive hand OA characterized by an abrupt onset, local inflammation, subchondral erosions and worse outcomes than non-erosive disease. Biomarkers of hand OA could help to diagnose the disease earlier, to distinguish patients with erosive and non-erosive forms, to assess disease severity or to predict its future progression. The objective of this review was to summarize the role of potential biomarkers of hand OA. A PubMed search for soluble biomarkers associated with hand OA was performed from inception to June 2017. In total, 21 relevant publications were found and reviewed. These publications identified 20 potential biomarkers of hand OA. C-terminal cross-linking telopeptide of type II collagen, cartilage oligomeric matrix protein, osteocalcin, hyaluronan, urinary pentosidine, vascular cell adhesion molecule 1, monocyte chemotactic protein 1, osteoprotegerin and interleukin 1 have been shown as potential biomarkers for assessing disease severity. C-terminal cross-linking telopeptide of type I collagen, hyaluronan, urinary pentosidine and myeloperoxidase were shown to differentiate between erosive and non-erosive hand OA patients. A number of biomarkers reflecting joint tissue metabolism and inflammation have been studied in hand OA. Some were identified as potential biomarkers of disease severity and progression, others were shown to differentiate between erosive and non-erosive disease. However, further research is necessary to assess the value of biomarkers for use in clinical practice.

Synovitis and radiographic progression in non-erosive and erosive hand osteoarthritis: is erosive hand osteoarthritis a separate inflammatory phenotype?

To compare the prevalence of synovitis, pain and radiographic progression in non-erosive and erosive hand osteoarthritis (HOA), and to explore whether the different rate of disease progression is explained by different levels of synovitis and structural damage. We included 31 and 34 participants with non-erosive and erosive HOA at baseline, respectively. Using Generalized Estimating Equations, we explored whether participants with erosive HOA had more synovitis (by MRI, ultrasound and clinical examination) independent of the degree of structural damage. Similarly, we explored whether pain at baseline and radiographic progression after 5 years were higher in erosive HOA, independent of the levels of synovitis and structural damage. All analyses were adjusted for age and sex. Power Doppler activity was found mainly in erosive HOA. Participants with erosive HOA demonstrated more moderate-to-severe synovitis, assessed by MRI (OR=1.73, 95% CI 1.11-2.70), grey-scale ultrasound (OR = 2.02, 95% CI 1.25-3.26) and clinical examination (OR=1.80, 95% CI 1.44-2.25). The associations became non-significant when adjusting for more structural damage. The higher frequency of joint tenderness in erosive HOA was at least partly explained more structural damage and inflammation. Radiographic progression (OR=2.53, 95% CI 1.73-3.69) was more common in erosive HOA independent of radiographic HOA severity and synovitis (here: adjusted for grey-scale synovitis by ultrasound). Erosive HOA is characterized by higher frequency and more severe synovitis, pain and radiographic progression compared to non-erosive HOA. The higher rate of disease progression was independent of baseline synovitis and structural damage.

AB0818 Bone Mineral Density and Metabolic Risk Factors in Patients with Non-Erosive and Erosive Hand Osteoarthritis

BackgroundHand osteoarthritis (OA) and its severe subset erosive hand OA are common causes of pain and morbidity in western world. Few studies investigated differences in systemic bone loss and metabolic...

Pentosidine, an Advanced Glycation End-Product, May Reflect Clinical and Morphological Features of Hand Osteoarthritis

The study investigates pentosidine levels, an advanced glycation end-product, in patients with erosive and non-erosive hand osteoarthritis (HOA) and determine its potential association with clinical findings and imaging-defined joint damage.Pentosidine was measured by HPLC in serum and urine of 53 females with HOA (31 erosive and 22 non-erosive HOA) and normalised to the total serum protein or urinary creatinine, respectively. Pain, joint stiffness and disability were assessed by the Australian/Canadian OA hand index (AUSCAN). The hand radiographs scored according to the Kallman grading scale were assessed to determine a baseline value and reassessed after two years.The levels of urine pentosidine, but not of serum pentosidine, were higher in patients with erosive HOA than in non-erosive HOA (p=0.039). Urinary pentosidine correlated with CRP (r=0.302, p=0.031), ESR (r=0.288, p=0.041) and AUSCAN (r=0.408, p=0.003). Serum pentosidine, but not in urine, significantly correlated with the Kallman radiographic score in erosive HOA at the baseline (r=0.409, p=0.022) and after 2 years (r=0.385, p=0.032). However, when corrected for age and disease duration, only correlation between urine pentosidine and AUSCAN remained significant (r=0.397, p=0.004).Our data suggest that serum and urine pentosidine levels may relate to the distinctive clinical and morphological features of HOA.

The model of erosive hand osteoarthritis

Hand osteoarthritis (OA) is not one disorder, but a heterogeneous group of disorders. Erosive HO (EOA) is a radiographic subset of hand OA and defined on the basis of radiographic central erosions and collapse of the subchondral bone plate. At the moment it is unknown whether EOA comprises a separate disease entity with specific risk factors and pathogenesis or a more severe stage of hand OA. EOA is a rather uncommon subset of OA. In the general population a prevalence of EOA in the interphalangeal joints (IPJs) of approximately 3% was estimated in adults aged 55 years and over. In the population with hand pain or with symptomatic hand OA the prevalence estimates were around 7% and 10%, respectively. However in a population with symptomatic hand OA from secondary care, the prevalence of EOA raised to 25%. The presence or absence of specific risk factors for EOA could learn whether EOA is a separate disease entity or a severe stage of hand OA. The first step in this research deals with heritable factors. Several studies suggest that EOA is heritable. Within patients with hand OA, several genetic factors are demonstrated to be associated with EOA when compared to non-erosive hand OA, but further replication of found results is needed. EOA is a highly clinical relevant subset, since EOA leads to a higher clinical burden and worse outcome than non-erosive hand OA. Patients with EOA report more pain and functional limitations, worse hand mobility, less satisfaction with hand function and aesthetics than those with non-erosive hand OA. However patients with EOA have also more nodes, which were also found to be a determinant of clinical outcome. Taking in account nodes, only hand mobility and patient satisfaction remained different between the groups. In the pathophysiology of EOA inflammation could be important. Already since 1972 it is noted that inflammation is involved in EOA, as also witnessed by histology of synovial biopsies of erosive DIPJs and PIPJs in an inflammatory stage, showing intense proliferative synovitis indistuinguishable from rheumatoid arthritis. Recently the presence and role of inflammation is further investigated by ultrasound and MRI studies. Moreover, ultrasound studies showed that not only in erosive but also in non-erosive joints in EOA more power Doppler signal and effusion is seen in comparison to joints in non-erosive hand OA, suggesting an underlying cause for erosive evolution. Another important observation is that erosions are more frequently present in hand OA than based on radiography when using ultrasound. The meaning of erosions only detected on MRI and ultrasound has to be elucidated. In conclusion, EOA is a highly clinical relevant subset of hand OA. Whether it is a separate disease entity is at the moment unknown, but needs further study. Inflammation seems of importance, already in the pre-erosive stages. Further research in this hand OA subset could lead to new treatments for patients with EOA.

Screening serum biomarker of knee osteoarthritis using a phage display technique

To screen serum biomarker of knee osteoarthritis (OA) using a phage random peptide library. A phage random peptide library of random peptide 12-mers was screened with purified immunoglobulin G (IgG) from sera of knee OA patients. Patients with knee rheumatoid arthritis (RA), hip OA, non-erosive hand OA or erosive hand OA, and healthy volunteers were used as controls. A phage clone with inserted peptide TGLESGHGPGDS (named KOA1) showed 90% positive reaction rate with the knee OA patients, significantly higher than that with the knee RA patients (27.8%), the non-erosive hand OA patients (34.3%), the erosive hand OA patients (31.3%) and the healthy controls (12.0%), but not the hip OA patients (82.5%). The novel knee OA mimic peptide KOA1 identified with a random phage display peptide library and sera from knee OA patients could be a potential serum biomarker for knee OA.

Hand osteoarthritis—a heterogeneous disorder

Hand osteoarthritis (OA) is a prevalent disorder. Hand OA is not one single disease, but a heterogeneous group of disorders. Radiographic signs of hand OA, such as osteophytes or joint space narrowing, can be found in up to 81% of the elderly population. Several hand OA subsets--such as nodal interphalangeal OA, thumb base OA and erosive OA--can be discriminated. Furthermore, the experience of symptoms and the course of the disease differ between patients. Studies that used well-defined study populations with longitudinal follow-up have shown that similarities and differences can be observed in the pathogenesis, epidemiology and risk factors of the various hand OA subsets. Erosive OA in particular, characterized by erosive lesions on radiographical images, has a higher clinical burden and worse outcome than nonerosive hand OA. Imaging modalities (such as ultrasonography) have increased our knowledge of the role of inflammation of the disease. Our understanding of the heterogeneous nature of hand OA can eventually lead to increased knowledge of the pathogenesis of, and ultimately new treatment modalities for, this complex disease.

Prevalence, incidence and progression of hand osteoarthritis in the general population: the Framingham Osteoarthritis Study

ObjectivesTo describe the prevalence and longitudinal course of radiographic, erosive and symptomatic hand osteoarthritis (HOA) in the general population.MethodsFramingham osteoarthritis (OA) study participants obtained bilateral hand radiographs at baseline and...

118 SYSTEMIC INFLAMMATION AND ANTIBODIES TO CITRULLINATED PEPTIDES IN HAND OSTEOARTHRITIS

ABSTRACTObjective. To investigate systemic in-flammation and autoimmune response to citrullinated peptides in patients with erosive and non erosive “lone” hand osteoarthritis (HOA) with no hip/knee involvement and their relationship with radiographic structural damage. Methods. Sera were obtained from a total of 99 patients with HOA (52 pa-tients with erosive HOA and 47 pa-tients with non-erosive HOA) and from 50 control subjects (NC). Hand radio-graphs were obtained from all patients and scored for joint damage according to the Kellgren-Lawrence and the Kall-man scores. Serum levels of high-sen-sitivity CRP (hsCRP), IL-6, pentraxin-3 (PTX-3), anti-CCP and anti-modified citrullinated vimentin (MCV) antibodies were evaluated by a sandwich ELISA.Results. Circulating levels of inflam-matory biomarkers hsCRP, IL-6 and PTX3 were not significantly different in the two groups of patients with erosive and non-erosive HOA compared to NC and no significant difference was seen between non-erosive and erosive HOA.Anti-CCP positivity was detected re-spectively in 1 patient (2.1%) with non-erosive HOA and 1 patient (1.9%) with erosive HOA. Anti-MCV antibod-ies were present in 4 patients (8.5%) with non-erosive HOA, and 4 patients (7.7%) with erosive HOA. In the con-trol group, one subject (2%) was posi-tive for anti-CCP and 2 subjects (4%) had anti-MCV antibodies.Significant correlation was obtained only between body mass index and hsCRP concentration (r=0.4071; p<0.0001). No correlation between inflammation markers/autoantibodies and disease duration and radiological scores was found. Conclusions. Our study underlines the lack of systemic inflammation and autoimmunity in “lone” HOA and con-firms the association between BMI and CRP levels.IntroductionLocal inflammation is increasingly rec-ognised as a contributing factor to the symptoms and progression of osteoar-thritis (OA) (1). Several studies have shown that the acute-phase response may take place in OA; indeed CRP may be slightly elevated in OA patients (1). Levels of high-sensitivity-C reac-tive protein have been reported to be associated with local inflammation in hip and knee OA patients (2) and high circulating levels of IL-6 are associated with the development of radiographic knee OA (3).Inflammatory mediators, such as TNF-α and IL-1, have been shown to induce CRP (albeit to a lesser extent com-pared to IL-6), an acute-phase protein belonging to the pentraxin family, as well as pentraxin-3 (PTX3). Evidence suggests that PTX3 is a useful new serological marker, rapidly reflecting tissue inflammation and damage under different clinical conditions (4). OA synoviocytes produce PTX3 (5), but no data on PTX3 systemic expression in OA patients are yet available.Inflammatory changes in joint tissue are triggered by innate and adaptive immu-nological mechanisms (1). Even though much remains to know about the trigger antigens in OA, autoantigens have been suggested as putative candidates. In inflamed rheumatoid joints, autoim-mune reactions lead to the production of antibodies against citrullinated pro-teins; recently antibodies against these proteins have also been found in the sera of other arthritides such as OA(6).In rheumatoid arthritis (RA), anti-CCP positivity showed the strongest asso-ciation with erosive arthritis (7) and the combined detection of antibodies against mutated citrullinated vimentin (anti-MCV), another type of citrullinat-ed protein, might improve the diagnos-tic and prognostic value of these tests in clinical practice (7). A subset of HOA is characterised by an inflammatory and erosive pattern, more severe symptoms, perimenopausal on-set and destructive changes involving the proximal and distal interphalangeal joints (8, 9). Therefore, erosive HOA is unique, sharing features typical of OA and inflammatory arthritis.Most studies addressing circulating bio-markers of inflammatory and autoim-mune response have focused on knee and hip OA, whereas data on HOA are scarce and the applicability of most results ob-tained in knee and hip OA is unknown.