Bone tissue metabolism in men with ankylosing spondylitis.

PURPOSE: The aim of the study was the composite estimation of bone tissue metabolism in ankylosing spondylitis (AS) after having taken into account such factors as a high risk of incidence of osteoporosis in patients with AS and potential danger of permanent immobility. MATERIAL AND METHODS: Sixty-six patients with established diagnosis of AS and 63 healthy individuals in the control group were included into the study. To measure bone mineral density (BMD) the dual energy X-ray absorptiometry (DEXA) method was used. Additionally, biochemical markers of osteoporosis such as bone fraction of an alkaline phosphatase (BALP), osteocalcin (BGP) and deoxypyridinoline (Dpd) as well as many inflammatory markers of disease activity have been determined. RESULTS: In our study with AS had significantly diminished bone mineral density, as compared with health controls. The presence of osteopenia/osteoporosis was associated with longer duration of the disease and with higher age. In the overall group of AS patients bone degradation marker, Dpd, correlated with serum concentration of interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-alpha) and C-reactive protein (CRP), and inversely with BMD measured in the forearm. However, no direct association could be revealed between lower bone density and markers of inflammation or inflammatory cytokines, except of IL-6 witch was significantly higher in AS patients with osteoporosis/osteopenia than those without. CONCLUSIONS: Our results indicate that disease duration and higher age are risk factors for osteoporosis in patients with AS. Inflammation might contribute to the accelerated bone loss in AS through stimulation of bone degradation.

[Bone tissue metabolism in systematic lupus erythematosus patients treated with glucocorticosteroids]. / Metabolizm tkanki kostnej u chorych na toczen rumieniowaty ukladowy leczonych glikokortykosteroidami.

The present study has been undertaken to evaluate bone turn-over in patients with systemic lupus erythematosus (SLE) treated with glucocorticosteroids. Thirty-eight patients with definite SLE has been investigated. The following parameters have been determinated. Some proinflammatory cytokine: interleukin-IL-1 alpha (IL-1 alpha), interleukin-IL-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), granulocyte-macrophage colony stimulating factor (GM-CSF) and some biochemical markers of osteoporosis: osteocalcin (BGP), alkaline phosphatase-bone formation (AP-B), procollagen type I carboxyterminal propeptide (PICP), carboxyterminal telopeptides of type I collagen (CTx) deoxypyridinoline (Dpd) and calcium/creatinin ratio have been determined. The forearm densitometry measurement was performed in all patients. We did not notice statistically significant decrease in bone mineral content and bone mineral density in spite of long term glucocorticosteroids treatment. Based on statistically significant correlation between carboxyterminal telopeptides of type I collagen (CTx) and calcium/creatinin ratio we observed increased bone resorption in analysed group of patients.

The presence of HLA-DR B1 shared motif does not influence cyclophosphamide and methotrexate cytotoxicity in rheumatoid arthritis patients.

In the present study we investigated the relation between cyclophosphamide and methotrexate toxicity and the presence of HLA- DR B1 alleles in rheumatoid arthritis patients. Seventy-eight such patients (67 women and 11 men) were observed for 12 months. Eighteen were treated with intravenous cyclophosphamide, 28 with oral methotrexate, and 32 with intramuscular gold salts. The prevalence of this shared motif was higher in the study population than in the healthy controls. However, detailed observations did not demonstrate a relation between particular genotype and drug intolerance. Based on the obtained findings we concluded that HLA-DR B1 typing cannot affect cyclophosphamide or methotrexate tolerance in rheumatoid arthritis patients. However, taking into account the relatively small number of patients expressing single genotype, further studies are recommended.

TNF-alpha gene polymorphism does not affect the clinical and radiological outcome of rheumatoid arthritis.

The present study was undertaken in order to investigate the relationship between tumor necrosis factor-alpha (TNF-alpha) gene polymorphism and the radiological progression of rheumatoid arthritis (RA) within the first 3-years of the disease. Sixty-eight RA patients (59 women and nine men) were observed for 3-years. TNF-alpha polymorphism analysis was performed in all patients. Radiographs of the hands were taken at the onset of study and after 3-years of follow-up. Radiographs were assessed according to the Larsen index (damage score and progression of damage score). We did not observe any correlation between TNF gene polymorphism and damage score or progression of damage score. The obtained data suggests that TNF-308 polymorphism cannot serve as an indicator of the disease course in RA patients.

Does the presence of HLA-DR B1 shared motif affect progression of the disease in rheumatoid arthritis patients?

The present study was undertaken in order to evaluate role of HLA DR Bl shared motif in prognosis of development of erosions in rheumatoid arthritis (RA). HLA genotyping was carried out in a retrospective analysis of 73 RA patients and 87 healthy controls using polymerase chain reaction. The assessment of disease activity was performed according to Mallya-Mace Index, whereas radiographs of hands were assessed according to the Larsen Index. HLA-DR4 and DR10 were significantly increased among RA patients. Relative risk was 7.540 and 4.646, respectively. Interestingly, the presence of DRl and DR14 did not enhance the relative risk in our group of patients. Determination of HLA-DR B1 alleles showed that among RA patients the most frequent was HLA-DR Bl*0401, *0404, and *0408. They gave a rise to a relative risk of 4.010, 7.540, and 3.686 respectively. For the purpose of analysis the patients were divided into three groups. The first group comprised 14 patients with two high-risk alleles (HLA DR B1 *01, *0401, *0404, *0408, *14). The second group gathered 35 patients with one high-risk allele. Twenty-four patients with no high-risk alleles were designated to the third group. We did not notice any differences in damage score and progression of damage score in rheumatoid arthritis patients with different number of high risk motifs. In conclusion, HLA-DR B1 shared motif was found to be significantly more frequent among analyzed erosive rheumatoid arthritis as compared to matched healthy controls. We did not observe any relation between the presence of shared motifs and outcome of the disease. Therefore, it seems that HLA DR B1 determination may very helpful in diagnosing or in establishing groups of risk but it is not likely to have a role in predicting development aggressive forms of RA.

[Bone tissue metabolism in patients with rheumatoid arthritis treated with glucocorticosteroids]. / Metabolizm tkanki kostnej u chorych na reumatoidalne zapalenie stawów leczonych glikokortykosteroidami.

The present study has been undertaken to evaluate bone turn-over in rheumatoid arthritis (RA) patients as well as the influence of low dose glucocorticosteroids (gcs) on bone mass loss. Ninety patients with establish RA has been investigated. The patients have been divided into two groups: 44 patients treated with gcs (age 52.5 +/- 12.4 years, disease duration 122 +/- 102 months, total dose of GCS, equivalent to prednisone -7.4 +/- 8.3 g) and 46 patients who were not treated with gcs (age 54.3 +/- 9.7 years, disease duration 134 +/- 120 month). Fifty patients have been assessed twice (after 12 month). Bone mineral content and bone mineral density have been determined in all patients in distal forearm. Additionally, some biochemical markers of osteoporosis: osteocalcin, alkaline phosphatase-bone formation, carboxyterminal telopeptides of type I collagen (CTx), procollagen type I carboxyterminal propeptide (PICP), deoxypyridynoline and some proinflammatory cytokine: IL-1 alpha, IL-6, TNF-alpha, GM-CSF has been determined. No difference in bone metabolism between RA patients receiving gcs treatment and those treated without gcs was shown. It is concluded that anti-inflammatory effect of gcs may balance the direct effect of gcs on bone mineral content in RA patients, particularly those with short term treatment.

Quantitative changes in peripheral blood lymphocytes in erosive rheumatoid arthritis patients treated with methotrexate. Correlation with disease activity.

In order to better understand the immunological mechanisms involved in the pathogenesis of rheumatoid arthritis (RA), the level of various lymphocyte subsets in the peripheral blood of 29 patients with erosive RA was determined. All the patients were treated with methotrexate for 2 years. The total number and the proportion of CD3 cells, CD3+CD4+ and CD3+CD8+ cells did not change during the study. The initially increased level of CD19+ B-cells and CD19+CD5+ cells decreased during the treatment. The percentage of CD3-CD16+ natural killer cells was not affected by the treatment. At the inception of the study, we observed a deficiency of CD4+ CD45RA+ cells and the level of CD3+CD29+ cells was slightly increased. During the treatment we noticed significant elevation of CD45RA cells. Consequently, the CD29/CD45RA ratio significantly decreased. We showed significant correlation between changes in disease activity and changes in the level of CD19+ cells and CD4+CD29+ cells. Our results suggest that low-dose methotrexate may affect immunocompetent cells. The lowering in the CD29+ subset population associated with depletion of CD19 B-cells after methotrexate therapy may limit abnormal CD4+ cell activation and reduce the migration of lymphocytes into inflamed synovium.

[The role of MHC class II genes in the etiopathogenesis of rheumatoid arthritis]. / Rola genów MHC klasy II w etiopatogenezie reumatoidalnego zapalenia stawów.

Rheumatoid arthritis (RA) is associated with HLA-DR4 and DR1 antigens. HLA-DRB1 gene sequences analysis demonstrated that only a limited set of alleles is positively associated with RA. Third hypervariable region sequences (70-74, 86) Q(R)R(K)RAA, G(V) are found in up to 95% of erosive RA. The presence of disease-associated allels may predict severe outcome of the disease. Therefore, their presence may allow us to start aggressive therapy in early stage of the disease.