Effect of cyclosporine A on bone density in female rheumatoid arthritis patients: results from a multicenter, cross-sectional study.

OBJECTIVE: To analyze the influence of cyclosporine A (CYA) on bone using data from a large multicenter, cross-sectional study on bone mineral density (BMD) in rheumatoid arthritis (RA). METHODS: We selected 558 female patients with RA and divided them into two groups on the basis of CYA use: those who had never used CYA (n = 467) and CYA users (n = 91; users for < 24 months n = 50; users for > 24 months n = 41). Demographic, disease and treatment-related variables were collected for each patient. BMD was measured at the lumbar spine and proximal femur using dual x-ray absorptiometry. Data was analyzed by means of a univariate and multivariate statistical procedure. Osteoporosis (OP) was defined as BMD < -2.5 T score. RESULTS: The frequency of OP among non-CYA users and CYA users was 28.2% and 33.3% (p=NS) for the lumbar spine, and 34.2% and 31.3% (p=NS) for the femoral neck, respectively. The prevalence of fragility fractures was not significantly different between the two groups. Mean values for the T-score at either the lumbar spine or the femoral neck were comparable in the two groups, even after adjustment for age, menopausal status, body mass index (BMI), Health Assessment Questionnaire (HAQ) score and steroid use. The generalized linear model showed that age, BMI and the HAQ score were significant independent predictors of BMD at the lumbar and femoral levels, whereas CYA use was not. Logistic analysis showed that only age, the HAQ score and BMI were significantly associated with the risk of OP. However, the duration of CYA therapy > 24 months was associated with an adjusted decreased lumbar BMD and a significantly decreased femoral neck BMD (p = 0.01). The frequency of femoral neck OP in patients on CYA for > 24 months was significantly higher than in patients on CYA for < 24 months: 46.4% vs. 19.44% (p=0.03), while the prevalence of fragility fractures did not differ significantly: 23.1% vs. 16.6%, respectively (p=NS). Logistic analysis showed that CYA use was an independent predictor of osteoporosis at the femoral site. CONCLUSION: Long-term CYA therapy may have negative effects on BMD in female RA patients.

Tolerability of tiaprofenic acid in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-linked genetic disorder which can lead to acute haemolytic anaemia following ingestion of fava beans and the administration of certain drugs, mainly in subjects with bacterial or viral infections. It is common in the Mediterranean region and many variants are found in Sardinia. The aim of this study was to evaluate in vivo if treatment with tiaprofenic acid 600 mg daily for 15 days would reduce erythrocyte GSH (reduced glutathione) concentrations and thus produce erythrocytolysis (assessed by evaluation of 51Cr-labelled erythrocyte survival) in subjects with G6PD deficiency. GSH concentrations were also evaluated in vitro after incubation of G6PD-deficient erythrocytes with increasing doses of tiaprofenic acid (20, 50, 100, 150 and 200 mg/L) and with acetylphenylhydrazine 5 mg. The results obtained both in vitro and in vivo confirmed the absence of any oxidative action of tiaprofenic acid on the erythrocytes of G6PD-deficient subjects.

Circulating telopeptide type I is a peripheral marker of thyroid hormone action in hyperthyroidism and during levothyroxine suppressive therapy.

The aim of the present investigation was to evaluate the clinical performance of serum carboxy-terminal-1-telopeptide (ICTP), a new marker of bone resorption, in identifying peripheral overexposure to thyroid hormones, as compared with serum osteocalcin (OC) and serum sex hormone binding globulin (SHBG). Serum ICTP, SHBG, and OC were assayed by specific radioassays in three study groups. Group 1: 50 perimenopausal women on long-term levothyroxine (LT4) suppressive treatment; group 2: 29 women with untreated hyperthyroidism; group 3: 36 normal euthyroid women matched with group 1 patients for age, alcohol, smoking habits, and lifestyle. Serum concentrations of SHBG, ICTP, and OC were markedly increased in hyperthyroid patients, whereas only serum ICTP was slightly but significantly increased in LT4 treated patients. Serum ICTP had higher diagnostic value for hyperthyroidism when compared with SHBG and to OC (sensitivity: 100%, 71%, 55%; accuracy: 97%, 88%, and 76%, respectively). In group 1, increased serum ICTP was observed in 30 of 50 patients, whereas increased SHBG and OC were found only in 11 of 50 (p < .001). Serum free thyroid hormone concentrations correlated with circulating ICTP and SHBG, and the correlation with serum OC was of lower significance. In conclusion, serum ICTP is a sensitive and reliable marker of peripheral thyroid hormone activity at the bone level; its clinical performance is higher than OC and even better than SHBG. Thus, serum ICTP is better than other peripheral markers in monitoring LT4 suppressive therapy in patients at increased risk for osteoporosis such as perimenopausal women.

Development of arthritis and hypothyroidism during alpha-interferon therapy for chronic hepatitis C.

Alpha-interferon (alpha-IFN) therapy may induce, reveal or exacerbate various autoimmune-related disorders. The most common is the development of autoantibodies, while clinically overt autoimmune diseases are rare. We describe a 49-year-old woman who developed seronegative rheumatoid-like arthritis and autoimmune hypothyroidism after 7 months of human lymphoblastoid alpha-IFN therapy given for hepatitis C virus-related chronic active hepatitis (CAH-HCV). There was no family or personal history of autoimmune, thyroid or articular diseases. Our patient required continuous therapy for arthritis and hypothyroidism despite discontinuation of alpha-IFN. This suggests that alpha-IFN therapy may induce the contemporary appearance of two different persistent autoimmune-related diseases in the same patient. However, chronic HCV infection may play an important adjuvant role in the development of these diseases.

Peripheral red blood cell survival invariance during pefloxacin treatment in subjects with glucose-6-phosphate dehydrogenase deficiency.

In order to evaluate the possible damaging effect of pefloxacin on erythrocytes in subjects with G-6-PD deficiency, a trial on red-cell survival was carried out using a 51Cr-labelled peripheral red blood cell technique. Eight men, aged 52 to 64 years, with osteoarthrosis and G-6-PD deficiency (Mediterranean type) were treated with 800 mg/day pefloxacin. Pefloxacin did not modify red cell survival in the subjects under study. In all subjects erythrocyte GSH levels were investigated in baseline conditions and also after incubation with increasing doses of pefloxacin. No significant change in erythrocyte GSH levels was observed after incubation with therapeutic doses of pefloxacin.

Safety of flurbiprofen in subjects with G-6-PD deficiency. In vivo and in vitro results.

The safety of flurbiprofen, a new non-steroidal anti-inflammatory drug was tested in individuals with G-6-PD deficiency. The study was carried out in vitro evaluating the erythrocyte levels of reduced glutathione under basal conditions and after incubation with the drug or acetylphenyl-hydrazine. In the red cells marked with 51Cr, survival was evaluated in vivo before and during flurbiprofen administration. The study shows that flurbiprofen has no oxidating activity in carriers of the G-6-PD Mediterranean variant.

[Physical activity and osteoporosis]. / Attività fisica ed osteoporosi.

The aim of the present research was to underline the importance of physical activity in the prevention and treatment of osteoporosis. Therefore the authors considered age-related bone loss and the value of weight-bearing exercise on bone-remodeling. Moreover the authors examined current world literature on physical exercise in post-menopausal age and bone mineral content in athletes, reporting their study's results.

[Ocular involvement in rheumatoid arthritis]. / Interessamento oculare in corso di artrite reumatoide.

The authors evaluated ocular involvement in 23 patients affected by rheumatoid arthritis (RA) according to ARA criteria. Slit-lamp biomicroscopic examination showed signs of keratoconjunctivitis sicca in one patient (4%), while a positive bilateral Schirmer test was found in six subjects (26%). Fluorescein angiography, carried out in 11 of the 23 RA patients, showed retinal vasculitis in 18% of the patients examined, even if no clinical and ophthalmoscopic signs of retinal vessel inflammation were present. The authors suggest that fluorescein angiography should be performed in patients affected by particularly active RA, with recent onset of the disease (< 12 months), high titres of classical IgM rheumatoid factor and raised concentrations of circulating immune complexes. The study confirmed moreover the uncommon ocular toxicity related to the drugs frequently employed in RA treatment (antimalarials, gold salts, glucocorticoids). Indeed, only one case (4%) of posterior subcapsular cataract clearly related to steroid therapy was found.

[Acromegalic arthropathy]. / L'artropatia acromegalica.

Six acromegalic patients, three males (aged 28 to 48 years) and three females (aged 57 to 75 years), with GH-producing pituitary adenoma, were studied through clinical examination, laboratory and instrumental tests. In all the patients frequent involvement of large joints, with crepitus and provoked pain, was found; while articular mobility was normal especially in the dorso-lumbar spine, a frequent seat of pain. Radiology showed typical features of an osteoarthritic process with characteristic widening of articular spaces, especially in weight-bearing large joints in symptomatic patients. The evolution of this arthropathy lead to anatomo-clinical pictures almost indistinguishable from osteoarthritis; however, in the early stages, the marked cartilaginous hypertrophy is responsible for peculiar anatomo-radiological pictures, principally represented by widening of articular spaces and intervertebral discal spaces, especially in the dorso-lumbar spine. As far as bone metabolism is concerned, neoproduction and reabsorption, both increased, proceed simultaneously; bone mass reduction is described in some segments. In our study, the two patients with active acromegaly showed bone mass reduction in the lumbar spine.

[Quantitative evaluation of HbA2. Comparison of 3 methods]. / Valutazione quantitativa della HbA2. Comparazione di tre metodiche.

Two electrophoretic tests and one based on column chromatographic method have been studied for quantitative and qualitative evaluation of HbA2. Results of 1069 assays demonstrated a satisfactory qualitative resolution for the three methods but for the best quantitative precision, the test of choice is the chromatographic one.

Serum and urine ferritin in patients with transitional cell carcinoma of the bladder.

Erythrocyte, serum and urine ferritin concentrations were evaluated in 20 patients suffering from transitional cell carcinoma of the urinary bladder and in 20 healthy men. No clinical or biochemical signs of liver disorders, chronic inflammatory states or infections were present in both the patients and the controls. Our results showed no significant difference in the erythrocyte ferritin concentration in both groups. On the contrary there was a statistically significant difference in mean serum (p less than 0.05) and urine (p less than 0.01) ferritin concentration between the two groups. The mean serum ferritin concentration in the patients was 102.23 +/- 63.38 ng/ml while it was 258.41 + 250.68 ng/ml in normal subjects. The mean urine ferritin concentration was 6.30 +/- 5.35 ng/ml in normal subjects and 22.66 +/- 25.59 ng/ml in patients with bladder cancer. Our data seem to demonstrate that the assessment of the ferritin either in the serum or preferably, in the urine, could become an interesting tumoral marker for bladder cancer.

Iron overload and lysosomal stability in beta zero-thalassaemia intermedia and trait: correlation between serum ferritin and serum N-acetyl-beta-D-glucosaminidase levels.

Increased iron storage represents a characteristic condition in patients with beta zero-thalassaemia intermedia. Iron overload is an important factor in cellular damage. Recent studies have shown an enhanced lysosomal fragility due to increased iron storage. 13 patients with beta-thalassaemia intermedia, aged 17-44 years, were studied. Both serum ferritin and serum N-acetyl-beta-D-glucosaminidase levels were evaluated in all subjects studied. A significant linear correlation (P less than 0.05) between serum ferritin and serum N-acetyl-beta-D-glucosaminidase levels were found.

A multicenter cross sectional study on bone mineral density in rheumatoid arthritis. Italian Study Group on Bone Mass in Rheumatoid Arthritis.

OBJECTIVE: To determine the frequency of osteoporosis in a large cohort of women with rheumatoid arthritis (RA) and to investigate the main determinants of bone mineral density (BMD) and risk factors for vertebral fractures in this population. METHODS: We recruited 925 consecutive female patients with RA at 21 Rheumatology Centers in Italy. For each patient pre-registered demographic, disease, and treatment-related variables were collected. BMD was measured at lumbar spine and proximal femur by dual x-ray absorptiometry technique. Collected variables underwent a univariate and multivariate statistical procedure. Osteoporosis was defined as BMD > -2.5 T score. RESULTS: The frequency of osteoporosis in the whole sample was 28.8% at lumbar spine and 36.2% at femoral neck and increased linearly from Steinbrocker's functional stage I to IV (p = 0.0001). Patients with spinal or femoral osteoporosis were significantly older (p = 0.0001), had a lower body mass index (BMI) (p < 0.02), a significantly longer disease duration (p < 0.02) and a significantly higher Health Assessment Questionnaire (HAQ) score (p = 0.0001). These differences were significant, even after adjusting for age. Steroid use was associated with significantly lower lumbar and femoral BMD (p = 0.0001) even after adjusting for the main confounding covariates. Analysis of lateral spine radiographs revealed 74 women with at least one vertebral fracture. These women had a significantly lower lumbar and femoral BMD (p = 0.0001). The generalized linear model showed that steroid use, menopause, BMI, age, and HAQ were all significant independent predictors of lumbar and femoral BMD. The logistic procedure showed that age (OR 1.05, 95% CI 1.03-1.07), HAQ (OR 1.3, 95% CI 1.07-1.7), menopause (OR 1.9, 95% CI 1.1-3.2), use of steroids (OR 1.5, 95% CI 1.07-2.1), and BMI (OR 0.8, 95% CI 0.8-0.9) were significantly associated with the risk for osteoporosis. The only variables associated with an increased risk for vertebral fracture were age (OR 1.04, 95% CI 1.01-1.08), HAQ (OR 1.7, 95% CI 1.08-2.09), and cumulative steroid intake (OR for 1 g of prednisone 1.03, 95% CI 1.006-1.07). CONCLUSION: To prevent osteoporosis and its dramatic complications in RA the therapeutic challenge is to preserve functional capacity using the lowest possible dosage of corticosteroids.