Duration Of Glucocorticoid Treatment Research Articles

Evaluation of glucocorticoid-induced osteoporosis in childhood kidney diseases by quantitative ultrasound

Objective To observe the glucocorticoid-induced osteoporosis(GIOP) in children with kidney diseases by quantitative ultrasound(QUS), and to analyze its influencing factors. Methods The tibia/radius bone mineral density(BMD) was checked obtained in 67 cases with childhood kidney diseases treated with glucocorticoid by QUS, BMD was measured in children over the age of 12 by dual-energy X-ray absorptiometry(DXEA), and BMD was measured with QUS consistency and different stages of osteoporsis were compared.The clinical data of gender, age, body mass index(BMI), administration duration and daily dosage of glucocorticoid were analyzed.The association between the duration of glucocorticoid use, and daily dosage of glucocorticoid and the different degrees of BMD was analyzed by Logistic regression analysis. Results Sixty-seven patients(male 45, female 22) were divided into 4 groups according to the reference standard of Asian children BMD data provided by Sunlight Company: the normal BMD group(41 cases), the mild osteoporosis group(18 cases), moderate osteoporosis group(5 cases), and severe osteoporosis group(3 cases). Both QUS and DEXA were highly correlated with BMD in patients measured(P>0.05). The duration of glucocorticoid treatment and daily dosage of glucocorticoid in 3 abnormal BMD groups were all significantly longer and larger than those of the normal BMD group(all P<0.05). Correlation analysis showed that BMI was positively correlated with the bone mass of the tibia(r=0.395, P<0.01). The duration of glucocorticoid treatment and daily dosage of glucocorticoid were negatively correlated with those of radius BMD(r=-0.474, -0.381, all P<0.01). Analysis showed that both the duration of glucocorticoid, and the daily dosage of glucocorticoid were the risk factors for GIOP. Conclusions QUS is a better method for evaluating of BMD and diagnosing of GIOP compared with DEXA in children.The daily dosage of glucocorticoid and the duration of glucocorticoid treatment are both the risk factors for GIOP. Key words: Glucocorticoid; Osteoporosis; Quantitative ultrasound; Tibia; Radius

Predictors of long-term remission after transsphenoidal surgery in Cushing's disease

There is no consensus on the remission criteria for Cushing's disease or on the definition of disease recurrence after transsphenoidal surgery, and comparison of the different published series is therefore difficult. A long-term recurrence rate of Cushing's disease ranging from 2%-25% has been reported. Predictors of long-term remission reported include: 1) adenoma-related factors (aggressiveness, size, preoperative identification in MRI), 2) surgery-related factors, mainly neurosurgeon experience, 3) clinical factors, of which dependence on and duration of glucocorticoid treatment are most important, and 4) biochemical factors. Among the latter, low postoperative cortisol levels, less than 2 mcg/dL predict for disease remission. However, even when undetectable plasma cortisol levels are present, long-term recurrence may still occur and lifetime follow-up is required. We report the preliminary results of the first 20 patients with Cushing's disease operated on at our hospital using nadir cortisol levels less than 2 mcg/dl as remission criterion.

Factors related to decreased bone mineral density in childhood cancer survivors

The risk of osteoporosis or osteopenia is known to increase after childhood cancer treatment. The purpose of this study was to evaluate patterns of bone mineral density (BMD) and factors related to decreased BMD in childhood cancer survivors. We studied 78 patients (34 males, 44 females) treated for acute lymphoblastic leukemia, acute myelogenous leukemia or chronic myelogenous leukemia during childhood. Clinical data, laboratory finding, bone age, lumbar BMD (LBMD) and femur neck BMD (FNBMD) were investigated. Chronological age at evaluation was 11.6±3.4 yr in males and 13.0±3.3 yr in females. Primary disease, chronological age at treatment, body mass index (BMI), method of treatment (chemotherapy, radiotherapy), endocrine function, presence of chronic graft-versus-host disease (cGVHD) and relevance of BMD standard deviation score (SDS) were evaluated. LBMD and FNBMD of the subjects were -0.91±1.41 and -1.13±1.79, respectively. Twenty (25.7%) patients had LBMD SDS lower than -2. Nineteen (24.4%) patients had FNBMD SDS lower than -2. The patients treated with hematopoietic stem cell transplantation had lower LBMD SDS (-1.17±1.39 vs -0.43±1.33, P=0.025). The risk of having LBMD SDS <-2 was higher in the patients treated with glucocorticoid for cGVHD (36.6% vs 13.5%; odds ratio [OR], 3.7; P=0.020). In multivariate logistic regression analysis, longer duration of glucocorticoid treatment (OR, 1.12; 95% confidence interval [CI], 1.03-1.22) and lower BMI SDS (OR, 0.42; 95% CI, 0.21-0.83) were associated with decreased LBMD SDS. These findings suggest that prolonged glucocorticoid use and reduction in BMI are risk factors for decreased BMD in childhood cancer survivors. Anticipatory follow-up and appropriate treatment are necessary, especially for the patients with risk factors.

THU0185 Independent risk factors of endothelial dysfunction (ED) and atherosclerosis (AS) development in patients with systemic lupus erythematosus (SLE)

BackgroundHigh-frequency of traditional risk factors of AS development is well-proven for patients (pts) with SLE. Significance of immunological and inflammatory factors, character of treatment and other factors were also reported....

A Search for Variables Predicting Cortisol Response to Low-Dose Corticotropin Stimulation Following Supraphysiological Doses of Glucocorticoids

To determine which biological or clinical variables may predict cortisol response to low-dose adrenocorticotropic hormone (ACTH) stimulation following supraphysiological doses of glucocorticoids in children. This retrospective study included all patients who underwent ACTH testing (1 μg) between October 2008 and June 2010 at the Sainte-Justine University Hospital Center, Montreal, after supraphysiological doses of glucocorticoids. Data from 103 patients (median age, 8.0 years; range, 0.6-18.5 years; 57 girls) were analyzed, revealing growth deceleration in 37% and excessive weight gain in 33%. Reasons for glucocorticoid treatment included asthma (n = 30) and hematologic (n = 22), dermatologic (n = 19), rheumatologic (n = 16), and miscellaneous (n = 16) disorders. The following information was recorded: duration of glucocorticoid treatment (median, 374 days; range, 5-4226 days); duration of physiological hydrocortisone replacement (median, 118 days; range, 0-1089 days); maximum daily (median, 200 mg/m(2)/day; range, 12-3750 mg/m(2)/day) and cumulative (median, 16 728 mg/m(2); range, 82-178 209 mg/m(2)) doses, in hydrocortisone equivalents; and interval since the last dose (median, 43 days; range, 1-1584 days). Sixty-two patients (58%) exhibited a normal response (ie, peak cortisol >500 nmol/L) to ACTH stimulation. Peak cortisol level was not related to sex, prior morning cortisol level, duration of treatment, or cumulative glucocorticoid dose; 28% of the patients with normal baseline cortisol levels nevertheless demonstrated a subnormal response to ACTH. Given the absence of clinical or biological predictors of the cortisol response to ACTH after suppressive doses of glucocorticoids, physicians have only 2 options: (1) empirically advocate glucocorticoid stress coverage during 18 months after cessation of high-dose glucocorticoid treatment; or (2) perform serial ACTH testing in all such patients until a normal peak cortisol level is attained.

Factores pronósticos de remisión a largo plazo tras cirugía transesfenoidal en la enfermedad de Cushing

There is no consensus on the remission criteria for Cushing's disease or on the definition of disease recurrence after transsphenoidal surgery, and comparison of the different published series is therefore difficult. A long-term recurrence rate of Cushing's disease ranging from 2%-25% has been reported. Predictors of long-term remission reported include: 1) adenoma–related factors (aggressiveness, size, preoperative identification in MRI), 2) surgery-related factors, mainly neurosurgeon experience, 3) clinical factors, of which dependence on and duration of glucocorticoid treatment are most important, and 4) biochemical factors. Among the latter, low postoperative cortisol levels, less than 2 mcg/dL predict for disease remission. However, even when undetectable plasma cortisol levels are present, long-term recurrence may still occur and lifetime follow-up is required. We report the preliminary results of the first 20 patients with Cushing's disease operated on at our hospital using nadir cortisol levels less than 2 mcg/dl as remission criterion.

Adverse Events During Longterm Low-dose Glucocorticoid Treatment of Polymyalgia Rheumatica: A Retrospective Study

To assess the occurrence of adverse events in a cohort of patients with polymyalgia rheumatica (PMR), treated with low-dose glucocorticoids (GC). This was a retrospective study by review of medical records. We identified 222 patients who had a mean duration of followup of 60 ± 22 months and a mean duration of GC therapy of 46 ± 22 months. We found that 95 patients (43%) had at least 1 adverse event after a mean duration of GC therapy of 31 ± 22 months and a mean cumulative dose of 3.4 ± 2.4 g. In particular, 55 developed osteoporosis, 31 had fragility fractures; 27 developed arterial hypertension; 11 diabetes mellitus; 9 acute myocardial infarction; 3 stroke; and 2 peripheral arterial disease. Univariate analysis showed that the duration of GC treatment was significantly associated with osteoporosis (p < 0.0001), fragility fractures (p < 0.0001), arterial hypertension (p < 0.005), and acute myocardial infarction (p < 0.05). Cumulative GC dose was significantly associated with osteoporosis (p < 0.0001), fragility fractures (p < 0.0001), and arterial hypertension (p < 0.01). The adverse events occurred more frequently after 2 years of treatment. Multivariate analysis showed that GC duration was significantly associated with osteoporosis (adjusted OR 1.02, 95% CI 1.02-1.05) and arterial hypertension (adjusted OR 1.03, 95% CI 1.01-1.06); GC cumulative dose was significantly associated with fragility fractures (adjusted OR 1.4, 95% CI 1.03-1.8). Longterm, low-dose GC treatment of PMR is associated with serious adverse events such as osteoporosis, fractures, and arterial hypertension; these adverse events occur mostly after 2 years of treatment.

Lack of association of high body mass index with risk for developing polymyalgia rheumatica

High body mass index (BMI) may have modulatory effects on the immune system. To determine the association between BMI and polymyalgia rheumatica (PMR) as well as the influence of BMI on glucocorticoid treatment duration and development of giant-cell arteritis (GCA) in patients with PMR. The BMI of 364 patients with PMR from a population-based incidence cohort was compared to the BMI of non-PMR subjects from the same population. High and low BMI were defined as > or = 25 and < 18.5 kg/m2, respectively. The association between BMI and case status was determined. The association between BMI and the duration of glucocorticoid therapy, as well as the development of GCA after accounting for relevant variables, were also examined. The mean BMI at index was similar in both groups (PMR: 26 +/- 5.4 kg/m2; non-PMR: 25.9 +/- 4.0 kg/m(2), P = 0.83). There was no association between BMI and the duration of glucocorticoid therapy. No significant association was found between BMI and the development of GCA in patients with PMR. Patients with high BMI (> or = 25 kg/m2) are not more likely to develop PMR. BMI did not influence the duration of glucocorticoid therapy or the occurrence of GCA in patients with PMR.

IL-6 May Modulate the Skeletal Response to Glucocorticoids During Exacerbations of Inflammatory Bowel Disease

Whether inflammatory cytokines affect the skeletal response to glucocorticoid (GC) treatment is unclear. Our objectives were to (1) identify the cytokine(s) elevated during exacerbations of inflammatory bowel disease (IBD); (2) determine whether the cytokine(s) identified in this way is related to systemic GC sensitivity; and (3) examine whether cytokines and/or measures of GC sensitivity are related to changes in bone formation or resorption following GC therapy. We designed a combined cross-sectional and prospective study, including patients with active (n = 31) and inactive (n = 34) IBD as well as controls (n = 29). We assessed circulating concentrations of cytokines, PINP and betaCTX, as well as GC sensitivity in peripheral blood mononuclear cells. IL-6 was the only cytokine increased in active IBD, 2.35 (2.63) versus 1.64 (1.21) versus 1.31 (2.79) pg/microl active IBD, inactive IBD, and controls, respectively (median [interquartile range]) (P = 0.03, ANOVA). IL-6 was positively related to magnitude of GC sensitivity (beta = 0.02, 95% CI 0.008-0.04, P = 0.005). Following treatment with GC in active IBD, PINP decreased (P < 0.001), whereas betaCTX showed no significant change (P = 0.2). Subsequently, multiple regression analyses revealed that plasma IL-6 concentrations were inversely related to the extent of PINP suppression following GC (beta = 3.3, 95% CI 0.2-6.4, P = 0.04, adjusted for baseline PINP and duration of GC treatment), while no association was observed with GC sensitivity. In conclusion, IL-6 is elevated in active IBD and may protect against GC-induced suppression of bone formation via a mechanism which appears to be independent of systemic GC sensitivity.

Urinary deoxypyridinoline is a BMD-independent marker for prevalent vertebral fractures in postmenopausal women treated with glucocorticoid

Urinary deoxypyridinoline (DPD) level was associated with prevalent vertebral fractures in glucocorticoid (GC)-treated postmenopausal women independently of lumbar spine bone mineral density (BMD). Bone metabolic indices are the potential predictors of bone fragility. However, their diagnostic efficiency for identifying the risk of GC-induced vertebral fractures is still unclear. We therefore evaluated whether bone metabolic indices would assess the risk of vertebral fractures in GC-treated women. One hundred seventy-five women treated with GC for more than 6 months were enrolled in this study. Both premenopausal and postmenopausal women with vertebral fractures had significantly higher urinary DPD levels than those without vertebral fractures. When multivariable logistic regression analysis was performed with the presence of vertebral fractures as a dependent variable and each of DPD or osteocalcin level adjusted for age, weight, height, current and maximum doses of GC, duration of GC treatment, as well as lumbar spine BMD as an independent variable, DPD level was identified as a factor associated with the presence of vertebral fractures in postmenopausal women but not in premenopausal women. Urinary DPD level was significantly associated with prevalent vertebral fractures in GC-treated postmenopausal women independently of lumbar spine BMD.

Deleterious Effects of Glucocorticoid Replacement on Bone in Women After Long-Term Remission of Cushing's Syndrome

Endogenous hypercortisolism and high-dose and long-term glucocorticoid (GC) therapy reduce bone mass. Patients in remission after successful treatment of Cushing's syndrome (CS) often present hypoadrenalism and require long-term GC replacement. The aim of our study was to evaluate whether this GC "replacement" had any further effect on bone in women after long-term remission of CS. Thirty-seven women (mean age: 50 +/- 14 yr; 27 of pituitary and 10 of adrenal origin) with cured CS (mean time of cure: 11 +/- 6 yr), 14 with active CS, and 85 sex-, body mass index (BMI)-, and age-matched controls were enrolled. BMD and BMC were measured by DXA scanning. Bone biochemical markers were also measured. Duration and dose of GC replacement and duration of endogenous hypercortisolism were calculated. Cured and active CS patients had less BMC, BMD, and osteocalcin than controls (p < 0.01). These differences were observed in estrogen-sufficient women but not in those with estrogen deficiency. Duration of GC treatment (mean: 42 mo; range, 2-420 mo) and endogenous hypercortisolism (mean: 70 mo; range, 13-241 mo) negatively correlated with BMC and lumbar spine BMD. After regression analysis, the main predictor of abnormal BMC and BMD was the duration of GC replacement (p < 0.01). Patients treated for CS persistently have less bone mass despite long-term cure. Both duration of endogenous hypercortisolism and mainly exogenous "replacement" therapy with GC negatively affect bone mass. Thus, the additional deleterious effect of GC for the treatment of adrenal axis suppression should be considered.

Is tacrolimus for childhood steroid-dependent nephrotic syndrome better than ciclosporin A?

The dosage and 3 months duration of glucocorticoidtreatment in steroid-sensitive childhood idiopathicnephrotic syndrome, mainly associated with thehistological picture of minimal change glomerulopa-thy, is based on the evidence of randomized clinicaltrials with clear-cut end points [1–3]. Duration of up to7 months of the therapy may even be more effective inachieving sustained remission. A further well-designedand adequately powered randomized controlled trial is,however, required. To avoid steroid toxicity, there isconvincing evidence for the use of oral cyclopho-sphamide in patients with frequent relapses [4]. Theevidence, however, is less stable for the treatment ofsteroid-dependent nephrotic syndrome (SDNS), i.e.recurrence of nephrotic syndrome within 2 weeks ofcessation of steroid treatment [5,6]. One of the majorconcerns with regard to the use of alkylating agentssuch as cyclophosphamide or chlorambucil in childrenand adolescents is gonadotoxicity [7]. Therefore,ciclosporin A (CSA) has been advocated when toxiceffects of prednisone and cyclophosphamide areexpected. CSA results in a remission rate of 85% inchildren with SDNS, bearing, however, the risk ofcalcineurin inhibitor-induced nephrotoxicity [8].Thus, alternative immunosuppressive drugs such asmycophenolate mofetil [9,10], rituximab [11] andsirolimus [12] are currently under investigation.Levamisol has been found to be of benefit in SDNSand has limited toxicity [13]. Data on the use of thecalcineurin inhibitor tacrolimus (TAC) are scarce.

The Threshold of Bone Mineral Density for Vertebral Fracture in Female Patients with Glucocorticoid-induced Osteoporosis

Glucocorticoid (GC)-induced osteoporosis (GIO) is a serious problem for patients taking GC therapy. GC increases risk for fracture. However, there are controversies regarding the threshold of bone mineral density (BMD) in patients with GIO. The present study aimed to examine the relationship between the presence or absence of vertebral fracture and various indices including BMD in 136 female Japanese patients treated with oral GC (102 patients with autoimmune diseases). Moreover, we analyzed the cut-off values of BMD for incidence of vertebral fracture in patients with oral GC use and compared these values with those in control subjects. BMD was measured by dual-energy X-ray absorptiometry of the lumbar spine, femoral neck, and distal one third of radius. We compared various indices between patients taking oral GC with and without vertebral fracture. Age, body height, and body weight were significantly greater, shorter, and lower in the group with vertebral fracture, respectively. As for BMD, age-matched BMD seemed lower in the fracture group, although the differences were significant between both groups only at the femoral neck. Duration of GC treatment was longer in the fracture group. Cut-off values of BMD at lumbar spine, femoral neck, and distal radius were higher in patients with GC treatment compared with those of control group [GC vs control (g/cm(2)): 0.807 vs 0.716 at lumbar spine; 0.611 vs 0.581 at femoral; 0.592 vs 0.477 at radius]. The sensitivity and specificity were lower in patients with GC treatment compared with those of control group. The present study demonstrated that the thresholds of BMD for vertebral fracture were higher in Japanese female patients with oral GC treatment at any site compared with postmenopausal subjects. The factors other than BMD were considered to affect bone strength and vertebral fracture risk.

Association of macrophage migration inhibitory factor gene −173 G/C polymorphism with prognosis in turkish children with juvenile rheumatoid arthritis

The objectives of this study were to determine genotypic and allelic frequencies of macrophage migration inhibitory factor (MIF) gene -173 G/C polymorphism in patients with juvenile rheumatoid arthritis (JRA) and to evaluate the association of the MIF -173 C allele with the outcome of JRA. Genomic DNA was collected from 67 JRA patients and 153 healthy individuals. To evaluate the association of the MIF -173 polymorphism with the outcome, we analyzed the data concerning the treatment regimen, duration of glucocorticoid treatment, score on the childhood health assessment questionnaire (C-HAQ) and the number of joints with active arthritis. Nonsignificant differences were observed between the study and control groups in the distribution of genotype and allele frequencies of the MIF gene -173 G/C polymorphism. In JRA patients, carrying a MIF -173 C allele, the number of disease modifying antirheumatic drugs required for the treatment was more, the duration of glucocorticoid treatment was significantly longer, and at the last visits the C-HAQ scores and the number of joints with active arthritis were significantly higher. MIF gene -173 C allele frequency did not differ between the controls and JRA patients. MIF -173 C allele did not confer increased susceptibility to JRA in our study group. Carriage of the MIF -173 C allele was found to be a strong predictor of poor outcome in all types of JRA.

Frequency of urinary tract infection among dogs with pruritic disorders receiving long-term glucocorticoid treatment

To determine frequency of urinary tract infection (UTI) among dogs with pruritic disorders that were or were not receiving long-term glucocorticoid treatment. Observational study. 127 dogs receiving glucocorticoids for > 6 months and 94 dogs not receiving glucocorticoids. Bacterial culture of urine samples was performed in dogs receiving long-term glucocorticoid treatment, and information was collected on drug administered, dosage, frequency of administration, duration of glucocorticoid treatment, and clinical signs of UTI. For dogs not receiving glucocorticoids, a single urine sample was submitted for bacterial culture. Multiple (2 to 6) urine samples were submitted for 70 of the 127 (55%) dogs receiving glucocorticoids; thus, 240 urine samples were analyzed. For 23 of the 127 (18.1%) dogs, results of bacterial culture were positive at least once, but none of the dogs had clinical signs of UTI. Pyuria and bacteriuria (present vs absent) were found to correctly predict results of bacterial culture for 89.9% and 95.8% of the samples, respectively. Type of glycocorticoid, dosage, frequency of administration, and duration of treatment were not associated with frequency of UTI. None of the urine samples from dogs not receiving glucocorticoids yielded bacterial growth. The frequency of UTI was significantly higher for dogs treated with glucocorticoids than for dogs that had not received glucocorticoids. Results suggest that dogs receiving long-term glucocorticoid treatment have an increased risk of developing a UTI. On this basis, we recommend that urine samples be submitted for bacterial culture at least yearly for such dogs.

Functional and prognostic relevance of the -173 polymorphism of the macrophage migration inhibitory factor gene in systemic-onset juvenile idiopathic arthritis.

To address the functional and prognostic relevance of the -173 single-nucleotide G-to-C polymorphism of the macrophage migration inhibitory factor (MIF) gene in patients with systemic-onset juvenile idiopathic arthritis (systemic-onset JIA) by evaluating its association with serum and synovial fluid levels of MIF, with glucocorticoid requirement, and with the outcome of the disease. A total of 136 patients with systemic-onset JIA were studied, including 98 patients from the British Paediatric Rheumatology Study Group's National Repository for JIA and 38 patients who were followed up at the IRCCS Policlinico San Matteo (Pavia, Italy) and the IRCCS G. Gaslini (Genoa, Italy). The MIF-173 polymorphism was genotyped using SnaPshot ddNTP primer extension and capillary electrophoresis. MIF levels were measured by enzyme-linked immunosorbent assay. The evaluation of the association of the MIF-173 polymorphism with outcome was performed only in Italian patients who were followed up for >5 years, by analyzing retrospectively 1) the number of joints with active arthritis and the number of joints with limited range of motion; 2) the score, at the last visit, on the Italian version of the Childhood Health Assessment Questionnaire (C-HAQ); and 3) data concerning the treatment regimens during the disease course. Systemic-onset JIA patients carrying a MIF-173*C allele had serum and synovial fluid levels of MIF significantly higher than those in patients with the GG genotype. The duration of glucocorticoid treatment on a daily regimen was significantly longer in patients carrying a MIF-173*C allele than in MIF-173 GG homozygous patients. Moreover, the duration of clinical response to intraarticular injection of triamcinolone hexacetonide was significantly shorter in patients carrying a MIF-173*C allele. At the last visit, the numbers of joints with active arthritis, the C-HAQ scores, and the numbers of joints with limited range of motion were significantly higher in patients carrying the MIF-173*C allele. Our study shows the functional relevance of the MIF-173 polymorphism and suggests that the MIF-173*C allele is a predictor of poor outcome in systemic-onset JIA.

Predominant factors associated with bone loss in liver transplant patients - after prolonged post-transplantation period.

Osteoporosis is a major cause of morbidity in liver transplant recipients and is associated with multiple factors. To evaluate bone mineral density (BMD), bone turnover and calcium-regulating hormones in 29 patients (17 men, 12 women) 2-12 yrs following liver transplantation for non-alcoholic liver diseases. Fifteen patients (52%) were on immunosuppressive treatment with tacrolimus and 14 (48%) with cyclosporine. Eleven patients (38%) were currently on prednisone, 18 patients (62%) had stopped glucocorticoid treatment 6 months to 11 yrs prior to the study. Nineteen patients (65.5%) had decreased BMD according to WHO criteria, 17 (58.2%) at the femoral neck, 13 (44.8%) at the lumbar spine. Nineteen patients (65.5%) had a subnormal (<15 ng/mL) serum level of 25 (OH) D3. These patients had significantly lower BMD at the femoral neck (p = 0.02). Femoral neck BMD negatively correlated with serum parathyroid hormone level (p = 0.06, r = -0.35), length of the post-transplantation period (p = 0.025, r = -0.416) and duration of glucocorticoid treatment (p = 0.029, r = -0.406), regardless of its cumulative dose. Symptomatic fractures were less frequent in tacrolimus treated patients than in cyclosporine users (p = 0.03). Decreased BMD is frequent following liver transplantation and is affected by vitamin D deficiency, cyclosporine use, and the duration of glucocorticoid therapy, but not by its cumulative dose. Achievement and maintenance of optimal vitamin D status and shortening of glucocorticoid treatment period may have a favorable effect on bone preservation.

Reduced bone mineral density in Japanese premenopausal women with systemic lupus erythematosus treated with glucocorticoids

We evaluated bone mineral density (BMD) in Japanese female patients with systemic lupus erythematosus (SLE) and assessed the influence of the use of glucocorticoids. Lumbar BMD was measured by dual x-ray absorptiometry (DXA) in 60 premenopausal females who previously had been receiving glucocorticoid therapy. Therapeutic- and disease-related variables for SLE were analyzed and bone resorption or formation markers were measured. Osteoporosis was defined as a T-score below 2.5 SD by DXA; 12 patients (20%) showed osteoporosis, and 30 (50%) had osteopenia. Compared with the nonosteoporotic group (n = 48), the osteoporotic group (n = 12) had a significantly longer duration of glucocorticoid treatment (P = 0.01), a cumulative prednisolone dose (P = 0.002), and an SLE damage index (SLICC/ACR). There was no difference in the incidence of osteoporosis either with or without the previous use of methyl-prednisolone pulse or immunosuppressive drugs. There was a significant positive correlation between urinary type I collagen cross-linked N-telopeptides (NTx) and serum bone-specific alkaline phosphatase (BAP) (r = 0.404, P = 0.002), but these bone metabolic markers showed no difference between the osteoporotic and nonosteoporotic groups. A good significant negative correlation was shown between BMD and the cumulative glucocorticoid dose (r = −0.351, P = 0.007). Stepwise logistic regression analysis showed that the cumulative glucocorticoid intake was independently associated with osteoporosis. Glucocorticoid-induced osteoporosis was frequently observed in Japanese SLE patients, as in Caucasian populations. The cumulative glucocorticoid dose was associated with an increased risk for osteoporosis. Bone metabolic markers such as NTx and BAP were not influenced by glucocorticoid treatment and could not predict current osteoporosis in SLE patients.

Comparison of chronic graft-versus-host disease after transplantation of peripheral blood stem cells versus bone marrow in allogeneic recipients: long-term follow-up of a randomized trial

AbstractIn a previous multicenter phase III trial comparing peripheral blood stem cell transplantation (PBSCT) to bone marrow transplantation (BMT) from HLA-matched related donors, we found no statistically significant difference in the cumulative incidence of clinical extensive chronic graft-versus-host disease (GVHD) in the 2 groups. We have analyzed the results in more detail to determine whether the clinical characteristics of chronic GVHD after PBSCT might be distinct from those that occur after BMT. Clinical extensive chronic GVHD developed in 39 of 63 recipients of PBSCs and in 32 of 63 BM recipients who were alive and free of malignancy at day 100 after the transplantation. No significant differences were found in the time and type of onset of clinical extensive chronic GVHD or in the frequency of complications associated with severe morbidity. Involvement of skin and female genital tract was more frequent in PBSC recipients than in BM recipients. The cumulative incidence of chronic GVHD at 3 years was similar in the 2 groups, but the number of successive treatments needed to control chronic GVHD was higher after PBSCT than after BMT (P = .03), and the duration of glucocorticoid treatment was longer after PBSCT compared to BMT (P = .03). These results suggest that chronic GVHD after PBSCT may be more protracted and less responsive to current treatment than chronic GVHD after BMT. Assessment of the overall benefits of PBSCT compared to BMT will require continued long-term follow up of morbidity associated with chronic GVHD.

Inflammation and bone metabolism in rheumatoid arthritis. Pathogenetic viewpoints and therapeutic possibilities

Systemic osteoporosis is a common and pathogenetically heterogenous complication in rheumatoid arthritis. Various factors such as disease activity, dosage and duration of glucocorticoid treatment and immobilization are involved in pathogenesis of osteoporosis in rheumatoid arthritis. Proinflammatory cytokines secreted by immunocompetent cells have a role in the regulation of the activity of osteoblasts and osteoclasts. The effects of these proinflammatory cytokines include the inhibition of bone formation and an increase in bone resorption. Interleukin-6 and nitric oxide induced in osteoblasts by proinflammatory cytokines are likely to be important mediators between these cytokines and the function of osteoblasts and osteoclasts. Furthermore, disease activity dependent changes in the secretion of glucocorticoids and in vitamin D metabolism may be involved in the pathogenesis of osteoporosis in this disease. Alteration of bone remodeling associated with immobilization is an important factor of systemic bone loss in rheumatoid arthritis. The inflammatory process in rheumatoid arthritis may cause penarticular and systemic bone loss by various cytokine and hormone mediated mechanisms. Concluding from these pathogenetic mechanisms, bisphosphonates and active vitamin D metabolites are likely to be effective therapeutic options in osteoporosis associated with rheumatoid arthritis.