The aim of our study was to analyse the serum interleukin-6 (IL-6), tumour necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta) and interferon-gamma (IFN-gamma) levels in patients with AS and their relationship with disease activity. An ELISA test was used to analyse serum cytokine (IL-6, TNF-alpha, IL-1 beta and IFN-gamma) levels in 69 patients with AS. Results were compared with those from 43 patients with RA and 36 patients with non-inflammatory back pain. The relationship between serum concentrations of the different cytokines and parameters of disease activity and severity in AS patients was also evaluated. IL-6 and TNF-alpha serum levels, but not IL-1 beta and IFN-gamma, were significantly higher in AS than in NIBP. However, patients with RA showed higher serum levels of IL-6, TNF-alpha and IFN-gamma than both AS and NIBP patients. In AS, IL-6 correlated with clinical parameters of disease activity with significant correlation being observed with laboratory parameters of inflammation such as ESR, CRP, platelet count and clinical parameters of severity such as vertebral mobility. TNF-alpha did not correlate with laboratory or clinical parameters of activity. Macrophagic cytokines (TNF-alpha and IL-6), are increased in AS patients and IL-6 closely correlated with the activity of the disease.

After liver transplantation there is a high incidence of fractures, with important rates of bone loss during the first months. However, the long-term evolution of bone mass and metabolism parameters have been scarcely studied. In order to determine the incidence and risk factors involved in the development of skeletal fractures and to analyze the long-term evolution of bone mass, bone turnover and hormonal status after liver transplantation, a 3-year prospective study was performed in 45 patients following liver transplantation. Serum osteocalcin, parathyroid hormone (PTH), 25-hydroxyvitamin D (25-OH D) and testosterone levels (men), and bone mass at the lumbar spine and femur were measured before and sequentially at different time points during 3 years. Spinal X-rays were obtained during the first year. Histomorphometric analysis of bone biopsies obtained in 24 patients within the first 12 hours after surgery and 6 months after transplantation was performed. Fifteen patients (33%) developed fractures after liver transplantation, and pre-transplant risk factors for fractures were age and low bone mass (odd's ratio for osteoporosis, 95% confidence interval: 5.69, 1.32-24.53). Serum PTH, osteocalcin, 25-OH D, testosterone and creatinine levels increased after transplantation. Moreover, PTH correlated with creatinine and osteocalcin values. Bone mass decreased during the first 6 months and reached baseline values at the lumbar spine the second year, with posterior significant recovery at the femoral neck. Long term evolution of femoral neck BMD correlated with PTH levels. Six months after transplantation bone histomorphometric data showed an increase in bone formation parameters. After liver transplantation there is a high incidence of fractures, specially in elderly patients and those with osteoporosis. Bone mass decreased in the short-term period and improved, initially at the lumbar spine and later at the femur, according to histomorphometric evidences of an increase in bone formation. The increase in creatinine values induces a secondary hyperparathyroidism that influences the changes in femoral bone mass. Treatment of osteoporosis shortly after liver transplantation may be important in the prevention of bone fractures, particularly in patients with low bone mass.

The purpose of this study was to determine the prevalence of osteoporosis, to estimate the bone turnover and hormonal status, and to identify the factors associated with bone disease in patients with end-stage liver disease who were referred for orthotopic liver transplantation. A prospective study was performed on 58 cirrhotic patients (6 with primary biliary cirrhosis, 14 with alcoholic cirrhosis, and 38 with posthepatitic cirrhosis), who were referred for orthotopic liver transplantation. Patients, excluding those with primary biliary cirrhosis, were classified in Child-Pugh groups according to the severity of liver disease (class B [28 patients], class C [24 patients]). Biochemical parameters of bone mineral metabolism and standard liver function tests were measured in all patients. Additionally, serum osteocalcin, urinary hydroxyproline/creatinine ratio, serum intact parathyroid hormone, serum 25-hydroxyvitamin D, serum 1,25-dihydroxyvitamin D, follicle-stimulating hormone, and luteinizing hormone levels were determined in patients and controls within the same age range. Plasma testosterone, sex hormone-binding globulin levels, and free testosterone index were obtained for all men included in the study. Bone mass of the lumbar spine and femur were measured by dual X-ray absorptiometry (DPX-L), and were expressed as a standard deviation of mean values (Z-score) from a sex and age-matched control group. Spinal X-rays were obtained to assess vertebral fractures. Osteoporosis was considered as a factor in spinal bone mineral density with a Z-score below 2 or at least one vertebral fracture. Twenty-five patients (43%) had osteoporosis, with lower bone mass measurements in the lumbar spine than in the femoral neck (P < 0.005). Alcoholic and Child-Pugh C patients showed the lowest femoral bone mineral density values. Cirrhotic patients showed lower osteocalcin levels than controls (14.3 +/- 5.9 vs. 18.2 +/- 8.1 ng/ml; P < 0.05) and showed increased urinary hydroxyproline (125.1 +/- 51.5 vs. 107.9 +/- 26.6 nM/mg creatinine; P < 0.05). Serum 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D and parathyroid hormone levels were significantly lower in cirrhotic patients than in controls (10.3 +/- 9.1 vs. 23.1 +/- 26.6 ng/ml; P = 0.000), (12.9 +/- 9.1 vs. 48.3 +/- 11.5 pg/ml; P = 0.000), (16.6 +/- 9.2 vs. 27.9 +/- 8.2 pg/ml; P = 0.000), with no differences between Child-Pugh groups. Alcoholic Child-Pugh C patients showed the lowest 25-hydroxyvitamin D serum values (4.5 +/- 2.2 ng/ml; P < 0.05). Male patients had lower testosterone levels than controls (302.5 +/- 229.4 vs. 556.7 +/- 146.5 ng/dl; P = 0.000), with increased sex hormone-binding globulin values. Levels of testosterone and gonadotropin were related to Child-Pugh classification. No correlation was found between bone mass and hormonal values. A significant decrease in bone mass, particularly in the lumbar spine, is seen in end-stage cirrhotic patients. Reduced bone formation and significant disorders of bone mineral metabolism, such as vitamin D deficiency, reduced p...

Objective-To investigate possible diVerences in Th1 and Th2 cytokine mRNA expression in the synovial tissue (ST) of patients with rheumatoid arthritis (RA) and seronegative spondyloarthropathies (SpA) with diagnostic and/or pathogenic interest. Methods-Eleven RA patients and 14 SpA patients (10 with undiVerentiated spondyloarthropathy (USpA), two with ankylosing spondylitis (AS) and two with psoriatic arthritis (PsA)) were included. Th1 (interferon , interleukin 2) and Th2 (interleukin 4, interleukin 5 and interleukin 10) cytokine mRNA levels from arthritic knee ST were quantified by using an optimised polymerase chain reaction method with a computerised analysis system. Protein levels of proinflammatory cytokines (interleukin 1, tumour necrosis factor and interleukin 6) in synovial fluid were quantified with a specific ELISA test. Results-Th1 cytokines were detected in all of RA ST samples in contrast with 58% (interferon ) and 71% (interleukin 2) of SpA samples. Th2 cytokines were expressed in 90% of RA ST samples, but the findings in SpA were interleukin 10 in 90%, interleukin 4 in 60% and interleukin 5 in 40% of ST samples. However, when the mRNA levels of each cytokine were quantified and corrected for T cell mRNA levels, only interferon levels were significantly higher in RA than in SpA (p<0.003). Thus, the Th1/Th2 cytokine ratio in RA was fivefold that of SpA. Synovial fluid interleukin 1 concentrations were higher in RA than in SpA (p<0.05); there were also higher synovial fluid levels of tumour necrosis factor in RA than in SpA, but without statistical significance. Conclusion-This study has detected both Th1 and Th2 cytokine gene expression in ST from RA and SpA patients. Synovium interferon mRNA levels and SF interleukin 1 protein levels were significantly higher in RA than in SpA, so reflecting the known proinflammatory activity of interferon through macrophage activation. Thus, the Th1 (interferon )/Th2 (interleukin 4) ratio is significantly higher in RA than in SpA ST. These data confirm previous studies on ST Th1/Th2 balance in RA and extend previous work in comparing ST RA with subgroups of SpA distinct of ReA.

Objective. To analyze whether inflammatory disease activity plays a substantial role in the loss of bone mass observed in ankylosing spondylitis (AS) patients who have not yet developed ankylosis.Methods. A longitudinal cohort study of 34 patients with early AS (duration <10 years) without ankylosis was conducted. The mean followup was 19 months. Loss of bone mass in defined regions of the lumbar spine and femoral neck was analyzed by dual x-ray absorptiometry. Patients were grouped according to biologic parameters of disease activity (erythrocyte sedimentation rate or C-reactive protein level). Group 1 consisted of 14 patients with active disease; group 2 comprised 20 patients with inactive disease. Serum levels of interleukin-6 (IL-6) and of hormones (sex, thyroid, and calciotropic), vertebral mobility (Schober test), daily physical activity, and treatment administered were recorded every 6 months for all patients.Results. At the end of the followup period, patients with active AS showed a significant reduction in bone mass in the lumbar spine (mean 1.01 gm/cm 2 at study entry versus 0.961 gm/cm 2 at followup [P ‫؍‬ 0.005]) and femoral neck (0.849 gm/cm 2 versus 0.821 gm/cm 2 [P ‫؍‬ 0.015]), which represented losses of 5% and 3%, respectively. In contrast, no significant reduction in bone mass was observed in patients with inactive AS. As expected, serum IL-6 levels were significantly higher in patients with active AS than in those with inactive disease (mean ؎ SD 8.3 ؎ 9 pg/ml versus 2.8 ؎ 5 pg/ml [P ‫؍‬ 0.008]). No significant differences were observed between the 2 groups in any of the other variables analyzed.Conclusion. The observation that loss of bone mass in AS occurred only in patients with persistent active disease strongly suggests that inflammatory activity of the disease itself plays a major role in the pathophysiology of the early bone mineral disorders observed in these patients.