The imbalance between osteoprotegerin and cathepsin K in the serum of patients with longstanding rheumatoid arthritis.

Osteoprotegerin (OPG) and soluble receptor activator of NF-kappa B ligand (sRANKL) together regulate the bone metabolism among other cytokines, whereby cathepsin K has a potent collagen-degrading activity. An imbalance of this system may be partly responsible for the skeletal complications of RA. Expanding on a previous study, we investigated the relationship between OPG, sRANKL and cathepsin K levels in the serum of patients with longstanding RA. We measured serum levels of OPG, sRANKL and cathepsin K of 100 patients with active, longstanding RA. We detected elevated serum levels of cathepsin K (median 54.8 pmol/l) and OPG (median 4.8 pmol/l), but normal sRANKL levels (median 0.2 pmol/l). Cathepsin K did not show a correlation with the overexpressed OPG (P=0.64) and sRANKL (P=0.81). The radiological destruction correlates significantly with cathepsin K (P=0.004) and OPG (P=0.007). We speculate that the increased levels of OPG are effective in compensating the action of sRANKL, but do not directly prevent bone degradation, as reflected by the elevated serum levels of cathepsin K.

Depressive symptoms in early rheumatoid arthritis: a comparative longitudinal study.

Our objective was to investigate symptoms of depression in early rheumatoid arthritis (eRA) patients, and follow them longitudinally during a 3-year prospective study of 73 Hungarian and 45 Austrian early rheumatoid arthritis patients. Compared to validated national population data, mild symptoms of depression were detected in Hungarian early rheumatoid arthritis patients, which were independent of corticosteroid use. In the Hungarian subgroup, the Beck Depression Inventory scores were found to be stable during follow-up. Except at the baseline visit, depressive symptoms and functional status, as measured by the Health Assessment Questionnaire, were correlated. Significant differences were detected between Austrian and Hungarian patients despite of their geographical and cultural proximity. The mean depression score was higher in the Hungarian when compared to the Austrian patients. Depression is an important feature of early rheumatoid arthritis. Studies assessing depression in rheumatoid arthritis patients must be based on validated national data of normal population.

Serum cathepsin K levels of patients with longstanding rheumatoid arthritis: correlation with radiological destruction.

Cathepsin K is a cysteine protease that plays an essential role in osteoclast function and in the degradation of protein components of the bone matrix by cleaving proteins such as collagen type I, collagen type II and osteonectin. Cathepsin K therefore plays a role in bone remodelling and resorption in diseases such as osteoporosis, osteolytic bone metastasis and rheumatoid arthritis. We examined cathepsin K in the serum of 100 patients with active longstanding rheumatoid arthritis. We found increased levels of cathepsin K compared with a healthy control group and found a significant correlation with radiological destruction, measured by the Larsen score. Inhibition of cathepsin K may therefore be a new target for preventing bone erosion and joint destruction in rheumatoid arthritis. However, further studies have to be performed to prove that cathepsin K is a valuable parameter for bone metabolism in patients with early rheumatoid arthritis.

Long-term benefits and repeated treatment cycles of intra-articular sodium hyaluronate (Hyalgan) in patients with osteoarthritis of the knee.

OBJECTIVES: To assess the long-term efficacy and tolerability of sodium hyaluronate (Hyalgan) after 1 cycle of 5 intra-articular (IA) injections in patients with osteoarthritis (OA) of the knee. The benefits of a second treatment cycle in patients with renewed need for therapy also were examined. METHODS: One hundred eight patients with knee pain (Kellgren-Lawrence grade 1, 2, or 3) for at least 20 days per month, and a score for pain on movement of at least 3.3 cm on a 10-cm Visual Analogue Scale (VAS) were treated with Hyalgan once weekly for 5 weeks in a multicenter, observational study. A repeat course was administered if patients continued to fulfill the inclusion criteria but not earlier than month 4. The primary efficacy parameter was pain on movement measured by VAS. Secondary parameters were pain on movement and pain at rest (5-point Likert ordinal rating scale), pain at rest (VAS), knee joint function (Larson scale), walking time, and global assessment of efficacy. RESULTS: The 59 patients completed the first 12-month follow-up period without the necessity for a second treatment cycle; 14 of the remaining 49 patients received a second treatment cycle. There were significant improvements in all efficacy parameters compared with the baseline values starting from 1 week after the last injection until month 12 for the 59 completed patients and also for all 108 enrolled patients (last observation carried forward). Safety and tolerability of Hyalgan were good or very good in more than 90% of patients. Of 4 patients who withdrew because of adverse events, only 1 event (knee joint effusion) was judged as possibly drug related. Two other adverse events judged to be drug related (generalized skin eruption; pruritus and knee joint effusion) resolved and did not lead to study withdrawal. CONCLUSION: The results of this observational study suggest that Hyalgan, administered either as a single or repeat course, is an effective and well-tolerated therapy for the long-term treatment of the pain of OA.

[Adverse effects of non-steroidal anti-inflammatory drugs. A prevalence study in Austria]. / Unerwünschte Wirkungen unter nichtsteroidalen Antiphlogistika. Eine Prävalenzstudie aus Osterreich.

OBJECTIVE: Gastrointestinal side effects are the limiting factor in the prescription of non-steroidal antirheumatic drugs (NSAID). However, there are no recent data from Austria. The aim of this prevalence study was therefore to assess the gastrointestinal risk from NSAID in Austria. METHODS: A total of 1347 patients were observed in an outpatient setting between March 2000 and February 2001. Side effects from NSAID were documented by questionnaire at two time points with a mean interval of 31 days. Documented data were analysed descriptively using an explorative strategy. The prevalence of side effects was compared to data from literature. RESULTS: Side effects were reported by 18.1% of the patients, severe gastro-intestinal complications (ulcer, bleeding, perforation) were diagnosed in 0.7%. Prescription of effective GI-protection (proton pump inhibitors, misoprostole, famotidin in high dose) was seen in only one third of the patients at risk. CONCLUSION: The prevalence of severe gastrointestinal side effects by NSAIDs assessed in our study was clearly lower than the prevalence reported in the Anglo-American literature. This may be due to a different prescription behaviour: about 75% of the patients took Diclofenac, lbuprofen or Meloxicam, drugs which have a very low potential of gastrointestinal complications. However, more information for general practitioners is needed yet to sufficiently protect patients at gastrointestinal risk from NSAID.

Evaluation of two different models of semi-automatic knowledge acquisition for the medical consultant system CADIAG-II/RHEUMA.

As part of a plan to promote semi-automatic knowledge acquisition for the medical consultant system CADIAG-II/RHEUMA, this study sought to explore and cope with the variability of results that may be anticipated when performing knowledge acquisition with patient data from different patient settings. Patient data were drawn both from a published study for the classification of rheumatoid arthritis (RA) and from a large database of rheumatological patient charts developed for the CADIAG-II/RHEUMA system. An analysis of the relationships between RA and selected CADIAG-II/RHEUMA symptoms was done using two models. In one of them, we controlled for the differences in baseline frequencies of symptoms and diseases in the two study populations as an important factor influencing the results of the calculations. Other factors that were identified included inconsistent definitions of symptoms and diseases, and the different composition of study groups in the two study populations. By eliminating differences in baseline frequencies as the most important bias, the results obtained from the two different knowledge sources became more consistent. All remaining inconsistencies and uncertainties about the contribution and relative importance of the factors were formalized using fuzzy intervals.