Prolactin in rheumatoid arthritis.
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Biomedical subjects
Publications and source records attributed to J M Nolla.
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BACKGROUND: Little information is available on the occurrence of generalized osteopenia in psoriatic arthritis. The only two published studies of bone mass in psoriatic arthritis produced conflicting results. METHODS: We compared bone mineral density measured at the lumbar spine and femoral neck using dual-energy X-ray absorptiometry in 52 patients with active peripheral psoriatic arthritis and in 52 controls. The psoriatic arthritis group included 19 males, 14 premenopausal women, and 19 post-menopausal women. Controls were matched to the patients on sex, age, and menopausal status. RESULTS: In the overall study population no significant differences were found between psoriatic arthritis patients and controls. Postmenopausal psoriatic arthritis patients had a lower femoral neck bone mineral density than the relevant subgroup of controls. No significant differences in lumbar spine bone mineral density were found in the analyses of the male, premenopausal female, and postmenopausal female subgroups. Neither was femoral neck density significantly different between male or premenopausal female psoriatic arthritis patients and controls. CONCLUSION: These results suggest that peripheral psoriatic arthritis is not associated with significant generalized bone loss.
We evaluated circulating aminoterminal and carboxyterminal propeptides of type I procollagen and total alkaline phosphatase levels in eighty consecutive patients affected by Paget's disease of bone. We compared the biochemical data with the extent of bone disease calculated on the basis of the bone scintigraphic indices. Serum aminoterminal propeptide of type I procollagen levels were high in 77% of patients, serum carboxyterminal propeptide of type I procollagen levels in 22% and serum total alkaline phosphatase levels in 76%. We found significant correlations between the three markers studied. The three biochemical markers correlated significantly with the bone scintigraphic activity indices, but the highest correlation coefficient was between the aminoterminal propeptide and total alkaline phosphatase. We conclude that there is a discrepancy between serum levels of the propeptides studied in relation to Paget's disease of bone. The sensitivity of the carboxyterminal propeptide of type I procollagen in this disease is low. In contrast the aminoterminal propeptide may be as sensitive a marker for the evaluation of this disorder as total alkaline phosphatase, and in addition may be more specific.
OBJECTIVE: To study changes in testosterone concentrations in saliva and total testosterone, free testosterone, and sex hormone binding globulin (SHBG) concentrations in serum in 2 groups of postmenopausal women with rheumatoid arthritis (RA), one group with glucocorticoid treatment and the other without it. METHODS: The above mentioned hormonal levels were measured in 20 postmenopausal women with RA undergoing glucocorticoid treatment, in 24 postmenopausal women with RA without treatment, and in 36 postmenopausal women without RA. RESULTS: We observed significantly lower levels of total testosterone in serum, SHBG in serum, testosterone in saliva, and the free testosterone index in the group of patients with RA undergoing glucocorticoid treatment compared to the group without treatment. We did not observe changes in free testosterone concentrations in serum of the groups studied, which is believed due to its lower specificity. CONCLUSION: Testosterone in saliva is a useful indicator for monitoring androgenic status in women with RA.
OBJECTIVE: High prolactin (PRL) levels have been reported in systemic lupus erythematosus, Reiter's syndrome, and psoriatic arthritis. However, results of PRL investigations in rheumatoid arthritis (RA) are contradictory. We evaluated the PRL status in men with RA and the possible effect on bone mineral density (BMD). METHODS: We studied 91 men with RA and 68 controls. PRL serum levels were analyzed under standardized conditions. Sex hormones (testosterone, androstenedione, and DHEAS) were also studied. BMD was analyzed at L2-L4 and the femoral neck by Hologic QDR1000. Comparative tests, linear correlations, and multiple regression analysis were performed. RESULTS: Serum PRL levels were significantly higher in men with RA (249+/-162 mU/l) than in controls (189+/-85 mU/l) (p=0.0015). High PRL levels were significantly correlated with the duration of RA (r=0.23; p=0.01) and with functional stage according to the Steinbrocker classification (r=0.24; p=0.01). High PRL concentrations were not correlated with the low levels of androgens observed in males with RA. Femoral BMD showed a negative correlation with PRL concentrations (r=0.20; p=0.04). Nevertheless, PRL was not a significant determinant of BMD. CONCLUSION: Men with RA have high serum PRL levels and concentrations increase with longer disease evolution and worse functional stage. Prolactin levels do not have a direct effect on BMD.
UNLABELLED: To investigate whether body morphology, obesity and its long time evolution were associated with lumbar and femoral bone mineral density (BMD) in premenopausal women of the same age. DESIGN: Cross-sectional study. SUBJECTS: 72 healthy premenopausal women born in 1950 (42 years) with a regular physical activity. MEASUREMENTS: BMD measured by dual-X-ray absorptiometry (DEXA) at lumbar spine and proximal femur; body weight, body mass index (BMI), BMI at 20 years (BMI-20), increase in BMI since age of 20 (BMI->20), body circumferences (breast, waist, hip) and their ratios (WHR, BHR, WBR), smoking and alcohol intake. RESULTS: Lumbar spine BMD did not correlate with any anthropometric measurement. Femoral BMDs correlated positively with weight, BMI, BMI-20, breast, waist, WHR and BHR. The BMI-20 explained the 5% and the current BMI the 13% of variance of total femur BMD. After adjustment for weight or BMI, breast circumference and BHR remained significantly correlated with all femoral BMDs sites except neck. Weight was the best predictor for neck BMD (R2 = 0.08; p < 0.02), and BHR for Ward's triangle (R2 = 0.12; p < 0.01) and trochanter (R2 = 0.10; p < 0.001). Alcohol intake, cigarette smoking, and age of menarche were not related to BMDs. CONCLUSION: In premenopausal women of the same age, lumbar spine BMD was not associated with any anthropometric measurement. Greater BHR and its long time of evolution may be determinants of greater femoral BMD (trabecular), whereas body weight may be determinant of femoral neck BMD (cortical). Further studies are needed to determine whether large breast to hip ratio may be considered as a protective factor for femoral osteoporosis.
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BACKGROUND: Soft-tissue sarcomas, malignant neoplasms originating from mesenchymal tissue, are rare but highly aggressive tumors. Present modes of therapy are associated with high rates of recurrence. 1, 25-Dihydroxyvitamin D3, the active metabolite of vitamin D, serves as a potent antiproliferative agent in human cancer cells. METHODS: In this study, six soft-tissue sarcoma cell lines were analyzed for vitamin D receptor (VDR) expression, which was then correlated with the degree of growth inhibition in response to 1, 25-dihydroxyvitamin D3. These cell lines included rhabdomyosarcoma (HS729, A204), fibrosarcoma (HS913t), synovial sarcoma (SW982), liposarcoma (SW872), and leiomyosarcoma (SKLMS-1). The level of VDR messenger RNA (mRNA) expression was determined using a ribonuclease protection assay, and functional receptor content was determined by using a ligand-binding assay. Growth studies, including [3H]thymidine uptake and growth curves, were performed on two of the six cell lines that expressed the highest and lowest receptor levels. RESULTS: Ribonuclease protection and ligand-binding assays demonstrated variable levels of VDR, with HS729 showing high expression and A204 showing no expression. In HS729, [3H]thymidine uptake was significantly decreased at 10(-7) M (33%) and 10(-6) M (40%) 1, 25-dihydroxyvitamin D3. Growth curve studies showed significant growth inhibition of 55% at 10(-6) M. A204 cells showed no growth inhibition upon treatment with 1, 25-dihydroxyvitamin D3. CONCLUSION: This study demonstrates the existence of VDR in soft-tissue sarcoma cells and suggests a correlation between the level of VDR in cells and the degree of growth inhibition caused by 1, 25-dihydroxyvitamin D3 which may potentially serve as an alternative form of therapy for soft-tissue sarcomas.
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A loss in bone mass was reported in premenopausal systemic lupus erythematosus (SLE) women, but this problem has not been studied in SLE males. We evaluated bone mineral density (BMD) in SLE males and the relationship between prolactin (PRL) and testosterone with BMD. We also studied the controversial effect of steroid therapy on BMD in these patients. We measured BMD in the lumbar spine and at the hip in 20 SLE men (mean age 37 y) and in the controls (n = 40). We measured PRL and testosterone in serum and saliva. The mean dose of prednisone at the time of study was 11.6 mg; and cumulative dose was 17.6 g. No significative decrease in BMD was detected in SLE males vs controls; either in the lumbar spine (1.00 +/- 0.1 vs 1.05 +/- 0.1 g/cm2) or in the femoral neck (0.84 +/- 0.1 vs 0.87 +/- 0.1 g/cm2). No patient or control had osteoporosis or fractures. We did not find any relationship between BMD and cumulative dose and baseline dose of corticosteroids. The mean values of PRL and testosterone (serum and salivary) were in the normal range. We did not find any correlation between BMD, PRL and androgens. This study did not show a loss in bone mass in SLE men on corticosteroid therapy.
OBJECTIVE: To study the bone mineral density (BMD) in premenopausal women with systemic lupus erythematosus receiving glucocorticoids (GL) and at 6 months, when the dose of GL was decreased to a level below half of the initial dose. METHODS: Twelve premenopausal women with SLE were prospectively studied after initiating prednisone therapy at a dose > or = 0.5 mg/kg/day. A densitometric study was performed (Hologic 1000 QDR) of the lumbar spine and femoral neck. Levels of osteocalcine (BGP), catacalcine (PDN-21), testosterone in plasma and saliva, and dehydroepiandrosterone sulphate (DHEAS) were measured. Measurements were repeated after 6 months. RESULTS: The initial mean dose of prednisone was 40 +/- 10.2 mg/day (0.66 mg/kg/day) with an accumulated dose of 27.6 +/- 23 g. Lumbar and femoral BMD were 1 +/- 0.13 and 0.831 +/- 0.07 g/cm2, respectively. A significant increase was observed in BGP an adrogen levels studied after a 6 months when the dose of GL was decreased to a mean dose of 13.9 +/- 7.5 mg/day (0.23 mg/kg/day), whereas no differences were found in BMD values. In none of the two phases of the study were osteoporosis, correlations between BMD and BGP, between PDN-21 and androgens or with the accumulated or punctual doses of GL documented. CONCLUSIONS: No decrease in BMD was observed after 6 months of therapy with high doses of GL. In contrast, an increase in BGP and androgenic status was observed when the GL dose was decreased.
OBJECTIVE: To evaluate bone mineral density (BMD) in premenopausal patients with systemic lupus erythematosus (SLE). METHODS: We measured BMD by dual energy x ray absorptiometry at lumbar vertebrae L2-4 and at the right femoral neck in 74 premenopausal white patients (mean age 30.8 years) with SLE who were receiving glucocorticoid therapy, and in a control group. RESULTS: The mean cumulative dose of prednisone was 32.5 (SD 28) g. The mean dose at the time of absorptiometry was 13.7 (6.9) mg. BMD was significantly reduced at the spine and at the femoral neck in SLE patients when compared with the control group: L2-4 = 0.943 (0.1) g/cm2 v 1.038 (0.1) g/cm2 (p < 0.001); femoral neck = 0.766 (0.09) g/cm2 v 0.864 (0.1) g/cm2 (p < 0.001). Nine patients (12.1%), but none of the control group, had a BMD less than the reference range. CONCLUSION: BMD in premenopausal patients with SLE was less than that in a control group and less than the reference range of values defining the presence of osteoporosis in 12.1%. We did not find a relationship between BMD and either cumulative or baseline dose of corticosteroid therapy.
OBJECTIVE: To determine whether limited joint mobility (LJM) is associated with microalbuminuria in type I diabetes mellitus. METHODS: Joint mobility was measured in a control group of 63 healthy subjects and in 63 type I diabetic patients, older than 18 years (mean 31.7 years, range 18-57), recruited from the outpatient clinic of the Endocrine Unit. Patients with established diabetic nephropathy (proteinuria or increased creatinine) were excluded. Joint mobility was assessed qualitatively with the prayer manoeuvre and quantitatively by measuring the angles of maximal flexion and extension of the fifth and third metacarpophalangeal (MCP) joints and wrist. Diabetic retinopathy was assessed by direct ophthalmoscopy. Urinary albumin excretion (UAE) was determined in at least two 24 hour urine samples. RESULTS: Joint mobility was limited in diabetic patients compared with control subjects. Diabetic patients with LJM had longer duration of diabetes (12.1 (SD 6.4) years compared with 6.9 (5.7) years; p < 0.001). Joint mobility was limited in patients with retinopathy: prayer manoeuvre was positive in 96.4% of patients with retinopathy, but in only 40.0% of patients with no retinopathy (p < 0.001); mobility of MCP joints and wrist was limited in diabetic patients with retinopathy even when the longer duration of their diabetes was taken into consideration. Microalbuminuria, present in 11 patients (17.5%), was associated with LJM: prayer manoeuvre was positive in 90.9% of patients with microalbuminuria, but in only 57.4% of patients with normal UAE (p < 0.05). Maximal flexion of MCP joints was reduced in patients with microalbuminuria. Microalbuminuria, but not LJM, was associated with risk factors of cardiovascular disease. CONCLUSION: LJM is associated with microalbuminuria and retinopathy in type I diabetes. The association is independent of age and duration of diabetes.
OBJECTIVE: Sex hormone status has been proposed as an important determinant of low bone mineral density (BMD) in both men and women. Our objective was to study the relationship between sex hormones and BMD in patients with rheumatoid arthritis (RA), and how steroid therapy affects both. METHODS: We studied 99 men with RA to assess their BMD and sex hormone status. A comparative group of 68 age paired men was used. We made comparative tests, linear correlations, and multiple regression analysis. RESULTS: We found significant reductions in lumbar BMD (p = 0.0005), femoral BMD (p < 0.0005), salivary testosterone (p = 0.01), androstenedione (p = 0.007), and dehydroepiandrosterone sulfate (DHEAS) (p = 0.03) in patients with RA. In contrast, serum testosterone concentrations were normal. Salivary testosterone showed correlation with femoral BMD (r = 0.36; p < 0.001). By multiple regression analysis, weight, serum testosterone concentrations, and the cumulative dose of corticosteroids were significant predictors of lumbar BMD (r = 0.41; p = 0.001). Weight, age, androstenedione concentrations, and the cumulative dose of corticosteroids were the significant predictors of femoral BMD (r = 0.79; p < 0.0005). CONCLUSION: We confirm there is reduced BMD in men with RA; corticosteroids contribute, but are not the only factor in the pathogenesis of low BMD in patients with RA; we found decreased levels of androstenedione, DHEAS, and salivary testosterone in men with RA; and salivary testosterone, as with free testosterone, is correlated with BMD in patients with RA, with lower levels contributing to low BMD.
Amyloidosis secondary to rheumatoid arthritis is a complication with a poor prognosis and as yet an undefined medical therapy. In the last decades the use of different cytostatics has been advocated to avoid renal function deterioration. The clinical characteristics and course in eight patients with amyloidosis secondary to rheumatoid arthritis are here reported after therapy with low dosage methotrexate. In twelve patients who followed a 12-month therapy a clinical improvement was observed, with a marked decrease in proteinuria; in one of them proteinuria disappeared. These results suggest that methotrexate at low doses might be an alternative in the early treatment of amyloidosis secondary to rheumatoid arthritis in patients with preserved renal function.
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OBJECTIVE: To determine if there were changes in PDN-21 and calcitonin levels in women with systemic lupus erythematosus (SLE) treated with glucocorticoids. METHODS: Concentrations of PDN-21 and calcitonin were studied in 52 premenopausal women with SLE treated with glucocorticoids. Bone mineral density analysis was performed by dual energy x-ray absorptiometry. RESULTS: The values of PDN-21 in the SLE group were 354.6 +/- 230.6 pg/ml, significantly higher than healthy women (66.7 +/- 56.8 pg/ml) (p < 0.001). There was no difference in calcitonin values between the SLE and control groups. CONCLUSION: Glucocorticoid therapy in patients with SLE causes increases of PDN-21, probably due in part to the effect on the gastric mucosa of this treatment and subsequent secretion of gastrin.
OBJECTIVE: To establish the prevalence of antiphospholipid antibodies (aPL) in a group of patients with ankylosing spondylitis (AS). The relation of the antibodies with different clinical and analytical features was studied. METHODS: Eighty-four patients with AS (71 men) and 40 age and sex matched controls were studied. aPL determinations included: anticardiolipin antibodies (aCL) of the IgM, IgG, and IgA classes, the presence of lupus anticoagulant (LAC), and a false positive serologic test for syphilis. Comparisons between variables were done by Student t test, Mann-Whitney test and Chi squared test. Correlations between aPL and clinical variables were performed by Pearson coefficients. RESULTS: Twenty-four patients with AS (29%) has positive IgG aCL, compared with only 2 cases in the control group (5%) (p < 0.002). There were no differences in other aPL determinations between patients and controls. There was no correlation between the presence of aCL (IgG, IgM, or IgA) and LAC and the different aspects of the disease. Two patients fulfilled the criteria for antiphospholipid syndrome. CONCLUSION: Our results indicate the presence of IgG aCL in patients with AS higher than in the normal population but their relation with thrombosis and other systemic manifestations seems weak.