Clinical and radiological factors associated with erosive radiographic progression in hand osteoarthritis.

OBJECTIVE: To identify prognostic factors of erosive progression in hand osteoarthritis (OA). METHOD: One hundred and fifty-four patients with hand OA were selected from an earlier cohort. X-rays, clinical and demographic data at baseline were present. All patients were seen for a follow-up between January and March 2014. Interphalangeal (IP) finger joints were scored on both radiographs using the anatomical scoring system. Radiographic progression was defined as a joint progressing from at least one anatomical phase, excluding the progression from a 'Normal' to 'Stationary' phase. Odds ratios (OR) and 95% confidence intervals (95% CI) of potential clinical and radiographic prognostic factors were calculated on joint, hand and patient level with a generalized estimating equation (GEE) model. RESULTS: Radiographic progression, including progression from 'N' to 'S' phase, was present in 1014 of 2750 joints (36.9%) after a mean follow-up of 5.8 years. On joint level, the following clinical factors were associated with radiographic progression (OR [95% CI]): presence of pain (1.48 [1.01-2.15]), tenderness (2.18 [1.56-3.05]), and soft tissue swelling (2.56 [1.54-4.24]). The following radiographic variables were significantly associated with erosive progression: presence of 'J' (16.74 [9.09-30.83]) and 'E' phase (76.34 [42.17-138.23]). On hand and patient level, soft tissue swelling, 'J' and 'E' phase were retained as prognostic factors. CONCLUSION: Pain, tenderness, soft tissue swelling, 'J' and 'E' phase were significantly associated with erosive progression in hand OA. These prognostic factors should be confirmed in further studies and considered when selecting patients for therapeutic trials with potential disease-modifying osteoarthritis drugs (DMODs).

3 T DCE-MRI assessment of synovitis of the interphalangeal joints in patients with erosive osteoarthritis for treatment response monitoring.

OBJECTIVE: To study the value of 3 T dynamic contrast-enhanced (DCE)-MRI for assessment of synovitis of the interphalangeal joints in patients with erosive osteoarthritis (EOA) for treatment response monitoring. MATERIALS AND METHODS: The interphalangeal joints of fingers two to five were examined at 3 T MRI in nine patients with EOA. Two musculoskeletal radiologists recorded erosions, bone marrow oedema (BME), synovitis and osteophytes. Interobserver reliability was calculated using κ statistics. In six patients, DCE-MRI time intensity curves of synovitis in two affected joints were analysed. The maximum upslope, absolute and relative enhancement of synovitis were compared with MRI after 12 months of anti-tumour necrosis factor treatment. Intraobserver reproducibility was calculated using intra-class correlation coefficient. RESULTS: Interobserver reliability was 'good' for detection of erosions (κ = 0.70), BME (κ = 0.77) and synovitis (κ = 0.77), but 'poor' for osteophytes (κ = 0.12). Post-treatment DCE-MRI showed decreasing maximum upslope (p = 0.002) and absolute (p = 0.002) and relative (p = 0.01) enhancement compared to the initial scan. Intraobserver reproducibility of DCE-MRI was 'almost perfect' or 'strong' for all parameters. CONCLUSIONS: 3 T DCE-MRI demonstrates changes in time intensity curves of synovitis in EOA of the interphalangeal joints in a longitudinal study, indicating this technique is promising for monitoring therapy response.

First insights into human acetabular labrum cell metabolism.

OBJECTIVE: Hip labrum pathology has only begun to emerge as a significant source of groin pain in the last decade since the development of hip arthroscopy. Few data are available on the anatomy, histology and function of this structure. Moreover, no metabolic data exist at cellular level. The aim of this study was to characterize extracellular matrix (ECM) genes and pro-inflammatory mediators expressed by these cells. METHODS: Isolated human acetabular labrum cells were cultured in alginate beads for 10 days and additionally stimulated with interleukin (IL)-1 for 24 h. Gene expression levels and secretion of different ECM genes, enzymes and cytokines were examined by quantitative polymerase chain reaction (qPCR) and enzyme-linked immunosorbent assay (ELISA) to assess the metabolic characteristics of labrum cells. Articular chondrocytes and meniscus cells served as controls. RESULTS: Labrum cells expressed high levels of COL1A1 and low levels of COL2A1, aggrecan and SOX-9 compared to chondrocytes. However, COL2A1 was more expressed by labrum cells than by meniscus cells. The expression of matrix metalloproteinase (MMP)-1/-2/-9, ADAMTS-4 and IL-6 was significantly higher in labrum cells than in chondrocytes. IL-1 suppressed the ECM gene expression levels of labrum cells, but increased the expression levels and release of MMP-1/-3/-9/-13 and ADAMTS-4 and IL-6 by these cells. Remarkably, MMP-9 was only significantly upregulated in acetabular labrum cells. CONCLUSIONS: The findings in this study demonstrated that the acetabular labrum is populated with unique highly active fibrochondrocyte-like cells. These cells are capable of expressing and releasing pro-inflammatory enzymes and cytokines and react to a pro-inflammatory stimulus. In this way, they contribute obviously to disturbed tissue function in hip labrum pathology.

The combination of microfracture and a cell-free polymer-based implant immersed with autologous serum for cartilage defect coverage.

PURPOSE: The purpose of this short-term pilot study was to determine the clinical and MRI outcome of a combination of microfracture with a cell-free polymer-based matrix for the treatment of cartilage defects in the knee. METHODS: The technique was used for treatment of symptomatic cartilage defects in the knee. Five patients were prospectively evaluated during 2 years with use of the Knee injury and Osteoarthritis Outcome Score (KOOS), the Tegner activity scale and the visual analog scale (VAS). MRI data were analyzed based on the original and modified MOCART (Magnetic Resonance Observation of Cartilage Repair Tissue) scoring system at 6, 12 and 24 months of follow-up. RESULTS: A gradual clinical improvement was observed during the follow-up. Adverse reactions to the matrix were not observed. The scaffold was firmly fixed with the use of bioresorbable pins. Both MOCART scoring systems revealed no significant deterioration or improvement in the repair tissue during the follow-up period. However, the majority of the patients exhibited subchondral lamina and bone changes. The formation of an intralesional osteophyte was observed in one case. CONCLUSIONS: The key finding in this study was that this procedure is safe for the treatment of cartilage defects in the knee. The patients showed a gradual clinical improvement postoperatively. Sixty percent (3/5) of the defects were adequately (complete or hypertrophic) filled with repair tissue at 2 years of follow-up. LEVEL OF EVIDENCE: IV.

Short-term outcome of the second generation characterized chondrocyte implantation for the treatment of cartilage lesions in the knee.

PURPOSE: To evaluate short-term clinical and MRI outcome of the second generation characterized chondrocyte implantation (CCI) for the treatment of cartilage defects in the knee. METHODS: Thirty-two patients aged 15-51 years with single International Cartilage Repair Society (ICRS) grade III/IV symptomatic cartilage defects of different locations in the knee were treated with CCI using a synthetic collagen I/III membrane to cover the defect. Clinical outcome was measured over 36 months by the Knee injury and Osteoarthritis Outcome Score (KOOS) and Visual Analogue Scale (VAS) for pain. Serial magnetic resonance imaging (MRI) scans of 22 patients were scored using the original and modified Magnetic resonance Observation of Cartilage Repair Tissue (MOCART) system. RESULTS: The patients included in this study showed a significant gradual clinical improvement after CCI. The MRI findings of this pilot study were considered to be promising. No signs of deterioration were observed. A complete or hypertrophic filling was observed in 76.5% of the cases at 24 months of follow-up. No preventive effect of an avital membrane on the occurrence of hypertrophic repair tissue was observed on MRI. Three failures were observed among the 32 patients until now (9.4%). CONCLUSIONS: This investigation provided useful information on the efficacy of this treatment. The short-term clinical and MRI outcome are promising. Large-scale and long-term trials are mandatory to confirm the results and the reliability of this procedure. LEVEL OF EVIDENCE: IV.

Autologous matrix-induced chondrogenesis combined with platelet-rich plasma gel: technical description and a five pilot patients report.

PURPOSE: This pilot study was designed to describe the technical details and to present the preliminary outcome of autologous matrix-induced chondrogenesis (AMIC) combined with platelet-rich plasma gel, the so called AMIC plus technique, for the treatment of patellar cartilage defects in the knee. METHODS: The AMIC plus technique was used for the treatment of (osteo) chondral patellar lesions in the knee. The surgical technique is extensively described. Five patients were clinically prospectively evaluated during 2 years. MRI data were analysed based on the original MOCART (Magnetic Resonance Observation of Cartilage Repair Tissue) and modified MOCART scoring system. RESULTS: A clinical improvement became apparent after 24 months of follow-up. Both MOCART scoring systems revealed no significant deterioration or improvement of the repair tissue between one and 2 years of follow-up. However, all cases showed subchondral lamina and bone changes. The formation of intralesional osteophytes was observed in 3 of the 5 patients during the 2 years of follow-up. CONCLUSIONS: AMIC plus is feasible for the treatment of symptomatic patellar cartilage defects and resulted in a clinical improvement in all patients. The favourable clinical outcome of the AMIC plus technique was not confirmed by the MRI findings. LEVEL OF EVIDENCE: IV.

Proteome characterization of human articular chondrocytes leads to novel insights in the function of small heat-shock proteins in chondrocyte homeostasis.

OBJECTIVE: In recent years, studies have been initiated to disclose the proteome of human chondrocytes and cartilage. Despite these studies, comprehensive information of the chondrocyte proteome remains limited. This study aimed to further explore the proteome expressed by human knee chondrocytes, and to study the functional aspects of heat-shock protein 27 (HSP27), a protein related to the previously described alphaBcrystallin, in chondrocyte biology. METHODS: Chondrocytes isolated from human knee articular cartilage were cultured in a three-dimensional alginate culture system. To simplify the protein mixtures, proteins extracted from chondrocyte cell lysates were fractionated based on hydrophobicity and molecular weight. Proteins were digested and the resulting peptides were separated and identified by an on-line two-dimensional (2-D) nanoliquid chromatography (nanoLC)-system coupled to a quadrupole time-of-flight (Qq-TOF) mass spectrometer. Differential expression analysis of HSP27 was performed by Western Blotting and quantitative polymerase chain reaction (QPCR). The effects of HSP27 on chondrocyte biology were explored by suppression of HSP27 expression induced by RNA interference (RNAi). RESULTS: In this study, we identified proteins with unknown functions together with membrane proteins, transcription factors and other low abundant proteins, which have not yet been described in chondrocytes. Based on previous knowledge on the related protein alphaBcrystallin, we selected HSP27 from the chondrocyte proteome database. Differential expression analysis revealed a decreased expression of HSP27 in Osteoarthritic (OA) chondrocytes. RNAi experiments revealed that HSP27 is involved in interleukin-1beta (IL-1beta) induced IL-6 secretion. CONCLUSION: These findings highlight that small HSPs, especially HSP27, play a prominent role in the maintenance of human articular chondrocyte homeostasis.

MRI evaluation of a new scaffold-based allogenic chondrocyte implantation for cartilage repair.

AIM: The present study was designed to evaluate the implantation of alginate beads containing human mature allogenic chondrocytes for the treatment of symptomatic cartilage defects of the knee. MRI was used for the morphological analysis of cartilage repair. The correlation between MRI findings and clinical outcome was also studied. METHODS: A biodegradable, alginate-based biocompatible scaffold containing human mature allogenic chondrocytes was used for the treatment of symptomatic chondral and osteochondral lesions in the knee. Twenty-one patients were prospectively evaluated with use of the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and the Visual Analogue Scale (VAS) for pain preoperatively and at 3, 6, 9 and 12 months of follow-up. Of the 21 patients, 12 had consented to follow the postoperative MRI evaluation protocol. MRI data were analyzed based on the original MOCART (Magnetic Resonance Observation of Cartilage Repair Tissue) and modified MOCART scoring system. The correlation between the clinical outcome and MRI findings was evaluated. RESULTS: A statistically significant clinical improvement became apparent after 6 months and patients continued to improve during the 12 months of follow-up. One of the two MRI scoring systems that were used, showed a statistically significant deterioration of the repair tissue at 1 year of follow-up. Twelve months after the operation complete filling or hypertrophy was found in 41.6%. Bone-marrow edema and effusion were seen in 41.7% and 25% of the study patients, respectively. We did not find a consistent correlation between the MRI criteria and the clinical results. DISCUSSION: The present study confirmed the primary role of MRI in the evaluation of cartilage repair. Two MOCART-based scoring systems were used in a longitudinal fashion and allowed a practical and morphological evaluation of the repair tissue. However, the correlation between clinical outcome and MRI findings was poor. Further validation of these scoring systems is mandatory. The promising short-term clinical outcome of the allogenic chondrocytes/alginate beads implantation was not confirmed by the short-term MRI findings.

Sensitivity and specificity of criteria for spondyloarthritis in children with late onset pauciarticular juvenile chronic arthritis as well as their characteristics.

OBJECTIVE: To evaluate the sensitivity and specificity of criteria designed for spondyloarthritis in a university hospital treated population of children with late onset pauciarticular juvenile chronic arthritis and a control population. METHODS: Four sets of criteria especially designed for juvenile patients: Garmisch-Partenkirchen juvenile spondylitis criteria (= Garmisch), SEA (=seronegative enthesopathy and arthritis) syndrome, Enthesitis Related Arthritis (ERA), Atypical spondyloarthritis for children and two sets of criteria for patients without age specification (European spondyloarthropathy Study Group - ESSG and Amor) were evaluated in a cross-sectional way in a group of 43 consecutive patients with late onset pauciarticular juvenile chronic arthritis (LOPA) seen over a six-month period in the outpatient clinic. These criteria were analysed in 69 patients with other forms of juvenile chronic arthritis as well. The sensitivity and specificity were calculated for each set, as well as positive predictive value and likelihood ratio. The characteristics described in the different sets of criteria were separately evaluated in the LOPA patients and the other patients. RESULTS: For sensitivity, the Garmisch criteria scored the highest value (97.7%). However, sensitivity was significantly lower in two of the juvenile sets (SEA syndrome and Atypical spondyloarthritis), respectively 44.2% and 51.2%, as opposed to the other criteria (>85%; p<0.01 by Mc Nemar test). Specificity and positive predictive value (PPV) was the highest for the SEA syndrome criteria (98.5%, vs. 95.0%) followed by the ERA (95.6 % vs. 92.1 %) and the Garmisch criteria (94.2% vs. 91.3%). The positive likelihood ratio (LR+) was >10 in SEA (30.5), ERA (18.7) and Garmisch (16.8). The negative likelihood ratio (LR-) was <0.1 only in the Garmisch criteria (0.02). CONCLUSION: Sensitivity, specificity, PPV, LR+ and LR- for the Garmisch-Partenkirchen criteria suggest that they classify almost the same population as defined by LOPA. The SEA syndrome criteria, which were not designed to be classification criteria, being very specific, cannot be used in this patient population to classify a sufficient number of patients. The sensitivity and specificity for the ESSG criteria being similar in these children as in adults suggest they have similar characteristics. The Garmisch-Partenkirchen criteria and/or LOPA definition are major candidates for future research in identifying spondyloarthritis in juvenile patients.

Reversible changes in serum immunoglobulin galactosylation during the immune response and treatment of inflammatory autoimmune arthritis.

OBJECTIVES: Improved DNA sequencer-aided fluorophore-assisted carbohydrate electrophoresis (DSA-FACE) technology was used to monitor the changes in the galactosylation status of serum immunoglobulins during the immune response and therapy of autoimmune arthritis. METHODS: Collagen-induced arthritis (CIA) was induced in susceptible DBA/1 mice and the undergalactosylation status (UGS) of serum immunoglobulins was determined using the improved DSA-FACE technology. Prophylactic intravenous tolerisation with type II collagen as well as semitherapeutic treatment with dexamethasone (DEX) were performed and UGS was analysed. Next, the serum immunoglobulin glycosylation profiles of patients with rheumatoid arthritis (RA) and spondyloarthropathy (SpA) were studied and changes in the UGS scores during anti-tumour necrosis factor (TNF)alpha therapy followed. RESULTS: In the longitudinal CIA study, the undergalactosylation state of immunoglobulins was found to be significantly correlated with the clinical arthritis scores. Upon collagen-specific tolerisation as well as glucocorticoid semitherapeutic treatment, improvement of the clinical arthritis scores correlated with decreased levels of UGS. It was also demonstrated that withdrawal of DEX was associated with an increased UGS score. Interestingly, reversibility in the UGS was also shown during treatment of patients with RA and SpA with anti-TNFalpha. CONCLUSIONS: These findings demonstrate that the UGS of serum immunoglobulins changes during the disease course of CIA and that this UGS is inhibited by antigen-specific and antigen-independent treatment procedures. The observation that Ig galactosylation is a reversible process is also documented during treatment of patients with RA and SpA with anti-TNFalpha.

EULAR evidence-based recommendations for the diagnosis of hand osteoarthritis: report of a task force of ESCISIT.

OBJECTIVES: To develop evidence-based recommendations for the diagnosis of hand osteoarthritis (OA). METHODS: The multidisciplinary guideline development group, representing 15 European countries, generated 10 key propositions regarding diagnosis using a Delphi consensus approach. For each recommendation, research evidence was searched for systematically. Whenever possible, the sensitivity, specificity and likelihood ratio (LR) were calculated; relative risk and odds ratios were estimated for risk factors for hand OA. Quality of evidence was categorised using the European League Against Rheumatism (EULAR) hierarchy, and strength of recommendation was assessed by the EULAR visual analogue scale. RESULTS: Diagnostic topics included clinical manifestations, radiographic features, subgroups, differential diagnosis, laboratory tests, risk factors and comorbidities. The sensitivity, specificity and LR varied between tests depending upon the cut-off level, gold standard and controls. Overall, no single test could be used to define hand OA on its own (LR <10) but a composite of the tests greatly increased the chance of the diagnosis. The probability of a subject having hand OA was 20% when Heberden nodes alone were present, but this increased to 88% when in addition the subject was over 40 years old, had a family history of nodes and had joint space narrowing in any finger joint. CONCLUSION: Ten key recommendations for diagnosis of hand OA were developed using research evidence and expert consensus. Diagnosis of hand OA should be based on assessment of a composite of features.

Cross-cultural adaptation of the Dutch version of the Functional Index for Hand Osteoarthritis (FIHOA) and a study on its construct validity.

OBJECTIVE: To validate a cross-culturally translated and adapted Dutch version of the Functional Index for Hand Osteoarthritis (FIHOA) in patients with osteoarthritis (OA) of the hands and to evaluate its construct validity by comparing with the Australian/Canadian Osteoarthritis Hand Index (AUSCAN). METHODS: The FIHOA was translated into Dutch and cross-culturally adapted. The questionnaire was administered to 72 patients with hand OA (female/male ratio: 64/8, handedness: right: 62/left: 7/both: 3). A visual analogue scale (VAS) pain scale (100mm) and the AUSCAN questionnaire were also recorded. An item-item analysis was performed. Test-retest reliability (time interval: 5 days) was assessed in 21 patients with intraclass correlation coefficient (ICC) and Bland and Altman graphical method. Construct validity was assessed by Spearman rank correlation coefficient between the FIHOA and AUSCAN. RESULTS: Internal consistency was high (Cronbach's alpha=0.89). All items, except for one ('Are you able to clench the fist?'), and the mean total FIHOA scores were statistically different between the subgroups based on the VAS (mean total score=7.46 and 14.19, in a-/mild symptomatic and symptomatic group, respectively (P<0.001)). The Spearman's correlation between all subscales of the AUSCAN (pain, stiffness, functionality) and the FIHOA was good, especially with the subscale functionality (r=0.81, P<0.01). Test-retest reliability was excellent with an ICC of 0.96 for the total score and the Bland and Altman plot showing a homogeneous distribution of the differences. CONCLUSION: The psychometric properties of the Dutch version of the FIHOA are excellent. There is a good correlation between the FIHOA and all subscales of the AUSCAN, especially the subscale functionality.

Cyclodextrin polysulphate protects articular cartilage in experimental lapine knee osteoarthritis.

OBJECTIVE: To evaluate the in vivo chondroprotective effect of cyclodextrin polysulphate (CDPS) in a rabbit model of experimental osteoarthritis (OA). DESIGN: Experimental OA was induced in rabbits by anterior cruciate ligament transection (ACLT). Forty-eight hours post-surgery, the rabbits were randomised into three treatment groups (n=15 in each group) and a sham-operated control group. The rabbits were either injected subcutaneously with saline, 0.25 mg/kg CDPS or 1 mg/kg CDPS once a week for a period of 12 weeks, and their weight was monitored as a parameter for their general status. The animals were then sacrificed for macroscopic and histological assessment of the knee joints. RESULTS: At the lowest dose, CDPS treatment was unable to induce a significant improvement of cartilage degradation vs the saline control in the experimentally induced knee OA. However, subcutaneous injections of 1 mg/kg CDPS induced a marked inhibition (P<0.05) of osteophyte formation. Additionally, a significant reduction of cartilage degradation revealed an overall chondroprotective effect of CDPS at a concentration of 1 mg/kg. No significant effects on weight gain were noted. CONCLUSIONS: Systemic administration of CDPS is able to protect cartilage in vivo and can therefore be considered as a chondroprotective agent with structure modifying capacities.

Differential proteome analysis of normal and osteoarthritic chondrocytes reveals distortion of vimentin network in osteoarthritis.

OBJECTIVE: We conducted a proteome analysis of human articular chondrocytes, in order to identify proteins differentially expressed in chondrocytes during the progression of osteoarthritis (OA) and to characterize the phosphorylation status of these proteins. METHODS: The proteins of 20 samples of human chondrocytes obtained from the cartilage of human knees (six from healthy cartilage (NoNo), seven from visually intact zones (NoOA) and seven from visually damaged zones (OAOA) of OA cartilage from the same knee joint) were sequentially extracted and subjected to two-dimensional gel electrophoresis (2-DE). Protein expression patterns were subjected to statistical analysis and protein spots of interest were identified by electrospray ionization tandem mass spectrometry. RESULTS: We identified several protein spots, showing a differential expression between the sample groups. Cleaved vimentin was upregulated in OAOA samples, this was confirmed by 1-DE and Western blot. The possible impact of vimentin cleavage on the chondrocyte's cytoskeleton was illustrated by confocal microscopy analysis, which revealed a distorted vimentin organization in OA chondrocytes. In contrast, F-actin staining did not reveal differences. CONCLUSION: All together, this study revealed substantial alterations in the vimentin cytoskeleton in OA-affected human articular chondrocytes.

NKT cells: manipulable managers of joint inflammation.

The importance of T cell participation in the aetiology and pathogenesis of rheumatoid arthritis (RA) is now widely appreciated. The disease is mediated by activated pro-inflammatory, self-reactive T helper cells, instigating the chronic autoimmune response characteristic of rheumatoid inflammation. Natural killer T (NKT) cells are a distinctive population of T cells thought to protect self-tissues from damaging inflammatory immune responses, and are often recognized as a regulatory T cell subtype, regulating the magnitude or class of the immune response. Recently, a number of studies have provided insight concerning the role of NKT cells in different models of autoimmune joint inflammation, suggesting the involvement of this specialized T cell subset in controlling initiation and perpetuation of arthritic disease. The aim of this review is to provide rheumatologists with an introduction of the principal features of NKT cells, to give an overview of the data obtained in animal models of arthritis and to discuss the hypothesized mechanisms. Finally, we will speculate on future prospects with regard to NKT cell-targeted treatment of arthritic disease by use of glycolipids.

EULAR evidence based recommendations for the management of hand osteoarthritis: report of a Task Force of the EULAR Standing Committee for International Clinical Studies Including Therapeutics (ESCISIT).

OBJECTIVES: To develop evidence based recommendations for the management of hand osteoarthritis (OA). METHODS: The multidisciplinary guideline development group comprised 16 rheumatologists, one physiatrist, one orthopaedic surgeon, two allied health professionals, and one evidence based medicine expert, representing 15 different European countries. Each participant contributed up to 10 propositions describing key clinical points for management of hand OA. Final recommendations were agreed using a Delphi consensus approach. A systematic search of Medline, Embase, CINAHL, Science Citation Index, AMED, Cochrane Library, HTA, and NICE reports was used to identify the best available research evidence to support each proposition. Where possible, the effect size and number needed to treat were calculated for efficacy. Relative risk or odds ratio was estimated for safety, and incremental cost effectiveness ratio was used for cost effectiveness. The strength of recommendation was provided according to research evidence, clinical expertise, and perceived patient preference. RESULTS: Eleven key propositions involving 17 treatment modalities were generated through three Delphi rounds. Treatment topics included general considerations (for example, clinical features, risk factors, comorbidities), non-pharmacological (for example, education plus exercise, local heat, and splint), pharmacological (for example, paracetamol, NSAIDs, NSAIDs plus gastroprotective agents, COX-2 inhibitors, systemic slow acting disease modifying drugs, intra-articular corticosteroids), and surgery. Of 17 treatment modalities, only six were supported by research evidence (education plus exercise, NSAIDs, COX-2 inhibitors, topical NSAIDs, topical capsaicin, and chondroitin sulphate). Others were supported either by evidence extrapolated from studies of OA affecting other joint sites or by expert opinion. Strength of recommendation varied according to level of evidence, benefits and harms/costs of the treatment, and clinical expertise. CONCLUSION: Eleven key recommendations for treatment of hand OA were developed using a combination of research based evidence and expert consensus. The evidence was evaluated and the strength of recommendation was provided.

Hand radiology characteristics of patients carrying the T(303)M mutation in the gene for matrilin-3.

OBJECTIVE: To determine whether the recently described hand osteoarthritis (HOA)-associated T(303)M mutation in the gene for matrilin-3 (MATN3) is associated with specific radiological changes on hand radiographs. METHOD: Standard hand radiographs from 26 HOA patients carrying the T(303)M missense mutation in the MATN3 gene (T(303)M patients) were compared with those from 52 HOA controls matched for sex, age, and clinical disease severity. Two blinded readers scored the radiographs, using the Verbruggen-Veys anatomical scoring system for the interphalangeal and metacarpophalangeal joints and the OARSI atlas scoring system for the first carpometacarpal (CMC1) joints. A scoring system based on the latter was used for the scaphoid-trapezoid-trapezoideum (STT) joints. RESULTS: No particular distinguishing features were found in the T(303)M patients and the prevalence of erosive and cystic changes was similar to the control group. As a group, however, the T(303)M patients had more severe thumb-base affection, particularly in the STT joint. Thus, definite radiological OA in both CMC1 and STT joints and higher STT scores compared with CMC1 were significantly more common in patients carrying the T(303)M mutation. Radiological scores for joint-space narrowing (CMC1 and STT) and osteophytes (STT) were also significantly higher in the T(303)M patients. CONCLUSION: Patients carrying the T(303)M mutation in the gene for matrilin-3 express a form of HOA that is radiologically indistinguishable from idiopathic HOA in individual patients but they have more severe thumb-base involvement, particularly in the STT joint. This is the first described genetic mutation that is associated with a common form of osteoarthritis.

Chondroprotective drugs in degenerative joint diseases.

Catabolic cytokine and anabolic growth factor pathways control destruction and repair in osteoarthritis (OA). A unidirectional TNF-alpha/IL-1-driven cytokine cascade disturbs the homeostasis of the extracellular matrix of articular cartilage in OA. Although chondrocytes in OA cartilage overexpress anabolic insulin-like growth factor (IGF) and its specific receptor (IGFRI) autocrine TNF-alpha released by apoptotic articular cartilage cells sets off an auto/paracrine IL-1-driven cascade that overrules the growth factor activities that sustain repair in degenerative joint disease. Chondroprotection with reappearance of a joint space that had disappeared has been documented unmistakably in peripheral joints of patients suffering from spondyloarthropathy when treated with TNF-alpha-blocking agents that repressed the unidirectional TNF-alpha/IL-1-driven cytokine cascade. A series of connective tissue structure-modifying agents (CTSMAs) that directly affect IL-1 synthesis and release in vitro and down-modulate downstream IL-1 features, e.g. collagenase, proteoglycanase and matrix metalloproteinase activities, the expression of inducible nitric oxide synthase, the increased release of nitric oxide, and the secretion of prostaglandin E(2), IL-6 and IL-8, have been shown to possess disease-modifying OA drug (DMOAD) activities in experimental models of OA and in human subjects with finger joint and knee OA. Examples are corticosteroids, some sulphated polysaccharides, chemically modified tetracyclines, diacetylrhein/rhein, glucosamine and avocado/soybean unsaponifiables.