Cumulative Glucocorticoid Dose Research Articles

Increased large artery intima media thickness in adolescents with either classical or non-classical congenital adrenal hyperplasia.

Increased artery intima-media thickness (IMT) was found in adults with classical congenital adrenal hyperplasia (CAH). No data are available in patients with non-classical (NC) CAH. To evaluate IMT in adolescents with classical and NC CAH and to compare the results with those recorded in a control population. Eighteen adolescents with either classical (Subgroup A1) or NC CAH (Subgroup A2) were compared with 16 controls (Group B). All subjects underwent IMT ultrasonography measurement at different sites; results were correlated with clinical, metabolic, and insulin resistance (IR) data. When compared with Group B, both subgroups exhibited higher IMT values at all sites. No differences were found between classical and NC CAH. Univariate analysis of factors impacting on IMT of CAH patients demonstrated that: a) abdominal aorta (AA) IMT was positively correlated with cumulative glucocorticoid doses, triglyceride serum levels, and diastolic blood pressure SD score and negatively with androstenendione and ACTH levels; b) common carotid (CC) IMT was positively associated with triglycerides and triglyceride/HDL ratio. At multiple regression analysis, the independent positive predictors of AA and CC IMT were respectively triglyceride levels and triglyceride/HDL ratio. a) Even adolescents with NC CAH and not only those with classical form may be at higher risk of artery alterations; b) this risk is not necessarily associated with either obesity or waist/height ratio or dyslipidemia; c) an important role in the pathogenesis of artery alterations in CAH may be played by intermittent iatrogenic hypercortisolism and secondary IR.

Prevalence of Vertebral Compression Fractures and Associated Factors in Children and Adolescents with Severe Juvenile Idiopathic Arthritis

Vertebral fractures occur in patients with juvenile idiopathic arthritis (JIA), but data on their frequency and causes are scarce. Our cross-sectional study evaluated prevalence of compression fractures and associated factors in a high-risk pediatric population with severe JIA. Children and adolescents with a history of treatment-resistant polyarticular-course JIA for ≥ 5 years or systemic arthritis for ≥ 3 years were recruited. Clinical examination, dietary recall, laboratory measurements, bone mineral density (BMD) measurement by dual-energy X-ray absorptiometry, and spinal radiography were performed. Our study included 50 patients (41 girls), of whom 6 (12%) had systemic arthritis, with a median age of 14.8 years (range 7.0-18.7 yrs) and median disease duration of 10.2 years (range 3.9-16.8 years). Ninety-four percent had used systemic glucocorticoids (GC); the median total duration of GC treatment was 7.1 years (range 0-15.5 yrs). The median weight-adjusted cumulative GC dose for the preceding 3 years was 72 mg/kg (range 0-911 mg/kg). The median bone age-corrected lumbar spine and whole-body areal BMD Z-scores were -0.8 and -1.0, respectively. Twenty-two percent had vertebral fractures, mostly thoracic. Compression fractures were associated with high disease activity, high body mass index (BMI), and high recent cumulative GC dose, but not with disease duration or BMD. Thirty percent had sustained at least 1 peripheral low energy fracture. Twenty-six percent were deemed to have significantly compromised bone health. Severe JIA is associated with a significant risk of vertebral compression fractures. Associated factors include high disease activity, high BMI, and high recent GC exposure. Further studies are needed to establish optimal prevention and treatment guidelines.

Glucose tolerance, insulin sensitivity and β-cell function in patients with rheumatoid arthritis treated with or without low-to-medium dose glucocorticoids

ObjectivesTo compare glucose tolerance and parameters of insulin sensitivity and β-cell function between chronic glucocorticoid (GC)-using and GC-naive patients with rheumatoid arthritis (RA).MethodsFrequently sampled 75 g oral glucose tolerance tests...

The causes of death in Korean patients with systemic lupus erythematosus over 11 years

We investigated the causes of death and analyzed the prognostic factors in Korean systemic lupus erythematosus (SLE) patients. We evaluated 1010 patients with SLE who visited Seoul Saint Mary's Hospital from 1997-2007. Changing patterns in the causes of death were analyzed. Survival rate was calculated by the Kaplan-Meier method and the log-rank test. The risk factors for death were analyzed by multivariate logistic regression analysis. The 5-year survival rate was 97.8%. Over the period of the study, 59 deaths were observed. Among 44 patients who died in our hospital, the most common cause of death was infection (37.3%), with SLE-related death as the next most frequent cause (22.0%). In comparison with earlier data, the proportion of SLE-related deaths has fallen and the proportion of infections has risen. SLE-related death was the most frequent cause of early death, while infection was the most common cause of death in the overall population. In univariate analysis, damage related to SLE, cumulative glucocorticoid dose, mean glucocorticoid dose for 1 month before death, intravenous methylprednisolone therapy and cyclophosphamide treatment were associated with death (p < 0.001 each). The late onset of SLE and renal involvement were predictive factors of poor outcome (p = 0.03 and p < 0.001). In multivariate analysis, the risk factors for death were irreversible damage related to SLE, cyclophosphamide therapy and mean glucocorticoid dose for 1 month before death. The most common cause of death in Korean SLE patients was infection. The judicious use of immunosuppressive agents may be important to decrease infection and to improve survival in SLE patients.

Carotid atherosclerosis predicts incident acute coronary syndromes in rheumatoid arthritis

The role of atherosclerosis in the acute coronary syndromes (ACS) that occur in patients with rheumatoid arthritis (RA) has not been quantified in detail. We undertook this study to determine the extent to which ACS are associated with carotid atherosclerosis in RA. We prospectively ascertained ACS, defined as myocardial infarction, unstable angina, cardiac arrest, or death due to ischemic heart disease, in an RA cohort. We measured carotid atherosclerosis using high-resolution ultrasound. We used Cox proportional hazards models to estimate the association between ACS and atherosclerosis, adjusting for demographic features, cardiovascular (CV) risk factors, and RA manifestations. We performed carotid ultrasound on 636 patients whom we followed up for 3,402 person-years. During this time, 84 patients experienced 121 new or recurrent ACS events, a rate of 3.5 ACS events per 100 patient-years (95% confidence interval [95% CI] 3.0-4.3). Among the 599 patients without a history of ACS, 66 incident ACS events occurred over 3,085 person-years, an incidence of 2.1 ACS events per 100 person-years (95% CI 1.7-2.7). The incidence of new ACS events per 100 patient-years was 1.1 (95% CI 0.6-1.7) among patients without plaque, 2.5 (95% CI 1.7-3.8) among patients with unilateral plaque, and 4.3 (95% CI 2.9-6.3) among patients with bilateral plaque. Covariates associated with incident ACS events independent of atherosclerosis included male sex, diabetes mellitus, and a cumulative glucocorticoid dose of ≥ 20 gm. Atherosclerosis is strongly associated with ACS in RA. RA patients with carotid plaque, multiple CV risk factors (particularly diabetes mellitus or hypertension), many swollen joints, and a high cumulative dose of glucocorticoids, as well as RA patients who are men, are at high risk of ACS.

A systematic review of randomized controlled trials for pemphigus vulgaris and pemphigus foliaceus

A range of interventions has been described for the treatment of pemphigus; however, the optimal therapeutic strategy has not been established. We sought to evaluate the safety and efficacy of interventions for pemphigus vulgaris and pemphigus foliaceus. We undertook a systematic review and meta-analysis according to the methodology of the Cochrane Collaboration. We selected randomized controlled trials including participants with the diagnosis of pemphigus vulgaris or pemphigus foliaceus confirmed with clinical, histopathological, and immunofluorescence criteria. All interventions were considered. Primary outcomes studied were remission and mortality. Secondary outcomes included disease control, relapse, pemphigus severity score, time to disease control, cumulative glucocorticoid dose, serum antibody titers, adverse events, and quality of life. Eleven studies with a total of 404 participants were identified. Interventions assessed included prednisolone dose regimen, pulsed dexamethasone, azathioprine, cyclophosphamide, cyclosporine, dapsone, mycophenolate, plasma exchange, topical epidermal growth factor, and traditional Chinese medicine. We found some interventions to be superior for certain outcomes, although we were unable to conclude which treatments are superior overall. Many interventions for pemphigus have not been evaluated in controlled trials. All studies were insufficiently powered to establish definitive results. There is inadequate evidence available at present to ascertain the optimal therapy for pemphigus vulgaris and pemphigus foliaceus. Further randomized controlled trials are required.

Early post-transplantation hypophosphatemia is associated with elevated FGF-23 levels

We examined the hypothesis that high FGF-23 levels early after transplantation contribute to the onset of hypophosphatemia, independently of parathyroid hormone (PTH) and other factors regulating phosphate metabolism. We measured serum phosphate levels (sPi), renal tubular reabsorption of Pi (TmPi/GFR), estimated GFR (eGFR), intact PTH (iPTH), calcitriol, intact (int) and C-terminal (Cter) FGF-23, dietary Pi intake and cumulative doses of glucocorticoids in 69 patients 12 days (95% confidence interval, 10-13) after renal transplantation. Hypophosphatemia was observed in 43 (62%) of the patients 12 days after transplantation. Compared with non-hypophosphatemic subjects, their post-transplantation levels of intact and CterFGF-23 were higher (195 (108-288) vs 48 (40-64) ng/l, P<0.002 for intFGF-23; 205 (116-384) vs 81 (55-124) U/ml, P<0.002, for CterFGF-23). In all subjects, Cter and intFGF-23 correlated inversely with sPi (r=-0.35, P<0.003; -0.35, P<0.003, respectively), and TmPi/GFR (r=-0.50, P<0.001; -0.54, P<0.001, respectively). In multivariate models, sPi and TmPi/GFR were independently associated with FGF-23, iPTH and eGFR. Pre-transplant iPTH levels were significantly higher in patients developing hypophosphatemia after renal transplantation. Pre-transplant levels of FGF-23 were not associated with sPi at the time of transplantation. In addition to PTH, elevated FGF-23 may contribute to hypophosphatemia during the early post-renal transplant period.

High frequency of osteoporosis and fractures in women with dermatomyositis/polymyositis

Bone mass was only previously studied in juvenile dermatomyositis/polymyositis (DM/PM) patients. Therefore, the objective this study was to evaluate the prevalence of osteoporosis and fractures in adult DM/PM. Forty female DM/PM and 78 age-, gender-, and BMI-matched healthy controls were studied. Medical charts and clinical interviews of all patients were evaluated for demographic and clinical data, including disease activity, cumulative doses of glucocorticoid, menarche and menopause age, and fractures. Bone mineral density (BMD) using dual X-ray absorptiometry (DXA) were measured at lumbar spine (L1-L4) and hip. A decreased BMD in lumbar spine [0.902 (0.136) vs. 0.965 (0.141) g/cm(2), P=0.022] and femoral neck [0.729 (0.12) vs. 0.784 (0.127) g/cm(2), P=0.027] was observed in patients compared to controls. In addition, osteoporosis was more frequent in patients than in controls in both lumbar spine (20 vs. 3.8%, P=0.007) and the femoral neck (27.5 vs. 10.3%, P=0.016). Moreover, a high prevalence of fractures was found in patients in comparison to healthy subjects (17.9 vs. 5.1%, P=0.040; OR=3.92; CI 95%:1.07-14.33). Comparing DM/PM patients with (n=17) and without (n=23) osteoporosis/fractures, significant differences were observed regarding age [56.8 (11.9) vs. 48.3 (13.2) years, P=0.042], weight [62.05 (13.56) vs. 71.51 (11.46) kg, P=0.022] and frequency of post menopausal women (94.1 vs. 65.2%, P=0.0002). No differences were observed concerning height, lean mass, total fat mass, disease activity, mean value of creatine kinase, cumulative glucocorticoid dose, or bisphosphonate use. Logistic regression analysis revealed a negative association between the presence of osteoporosis/fractures and weight (OR: 0.92, 95% CI: 0.85-0.98; P=0.016). This is the first study that analyzed bone mass in adult DM/PM patients and it demonstrated that about one quarter of these patients have osteoporosis/fracture.

Damage accrual, cumulative glucocorticoid dose and depression predict anxiety in patients with systemic lupus erythematosus

The burden of anxiety in patients with systemic lupus erythematosus (SLE) compared to those with other inflammatory rheumatological conditions is unclear. We aimed to compare the frequency and level of anxiety between patients with SLE, rheumatoid arthritis (RA), and gout and healthy individuals and explore independent predictors for anxiety in SLE patients. Consecutive patients with SLE, RA and gout and healthy individuals who were age and sex matched with the SLE group were evaluated for anxiety using the Hospital Anxiety and Depression Scale (HADS). Sociodemographic and disease-related variables were compared between all groups. Predictors for anxiety were studied by regression models, with construction of a prediction model for the presence of anxiety in SLE patients by the receiver operating characteristic (ROC) analysis. Amongst 271 subjects studied, 60 had lupus, 50 had gout, 100 had RA and 61 were healthy controls. The frequency and level of anxiety were significantly higher in SLE patients than patients with gout, RA and healthy controls. SLE per se was independently associated with higher HADS-anxiety score after controlling for potential confounders. Logistic regression model showed that higher damage accrual, higher cumulative glucocorticoid dose, depression and fewer regular medications predicted anxiety in SLE patients, with an accuracy of 90% by the ROC analysis.

Risk Factors for Low Bone Mineral Density in Korean Patients with Systemic Lupus Erythematosus

Objective. To determine the degree and risk factors for decreased bone mineral density (BMD) in patients with systemic lupus erythematosus (SLE). Methods. One hundred and one patients with SLE and 57 age- and gender- matched healthy controls were enrolled in this study. The BMD was measured by dual energy X-ray absorptiometry (DXA). The laboratory findings and clinical variables evaluated in the SLE patients consisted of disease duration, SLE disease activity index (SLEDAI), and medications, including mean and cumulative dose of glucocorticoid. At the time of the clinical and laboratory assessment, the levels of serum osteocalcin, serum FSH/ LH, urine deoxypyridinoline (DPD), and serum cytokines, such as IL-6 and soluble receptor activator of NF-kB ligand (RANKL), were determined in SLE patients using a enzyme-linked immunosorbent assay. Results. The BMD T score decreased in patients with SLE compared to the healthy controls (−1.11 versus −0.41, p=0.001 at lumbar spine, −0.84 versus −0.01, p＜0.001 at femur neck, −1.20 versus −0.45, p＜0.001 at total hip, respectively). Osteoporosis and osteopenia was present in 16.8% and 46.5% of patients, respectively. Multiple regression analysis revealed a low BMD in the lumbar spine to be associated with increased FSH, low BMI and cumulative glucocorticoid dose. A low BMD in the hip and femur neck was associated with increased FSH, low BMI, and duration of glucocorticoid. On the other hand, the levels of osteocalcin, deoxypyridinoline (DPD), IL-6, and soluble RANKL were similar in patients with a low BMD and those with normal BMD. Conclusion. Osteoporosis and osteopenia are more common in young Korean SLE patients than in control subjects. Elevated FSH, low BMI, and the use of glucocorticoid are independent risk factors linked to a decreased BMD in Korean patients with SLE.

Incidence and risk factors of steroid-induced diabetes in patients with respiratory disease.

Glucocorticoids are effective for treating several respiratory diseases. However, they can cause hyperglycemia. This study determined the incidence and risk factors of steroidinduced diabetes mellitus (S-DM) in patients treated with glucocorticoid for respiratory diseases. A retrospective study examined patients with respiratory diseases treated with a prednisolone-equivalent glucocorticoid dose exceeding 20 mg/day for at least 4 weeks between January 2003 and December 2008. Patients whose initial random glucose level exceeded 200 mg/dL or who had pre-existing diabetes were excluded. S-DM was defined as a fasting glucose concentration exceeding 126 mg/dL or a random glucose concentration exceeding 200 mg/dL at least twice after beginning steroid treatment. A total of 231 patients with respiratory diseases met the inclusion criteria. Their median age was 55 yr, and 139 were female. The median cumulative prednisolone-equivalent glucocorticoid dose was 4,965 mg, and the median duration of steroid treatment was 193 days. S-DM was diagnosed in 34 (14.7%) of 231 patients. Multivariate logistic regression identified older age (odds ratio 1.05, 95% confidence interval 1.02-1.09) as a risk factor for S-DM. S-DM is frequent among patients with respiratory diseases treated with glucocorticoid. Clinicians should be aware of the possibility of S-DM, especially among elderly patients.

Age, Initial Dose and Dose Increase are Independent Risk Factors for Symptomatic Vertebral Fractures in Glucocorticoid-Treated Male Patients

The incidence and risk factors for symptomatic vertebral fracture were analyzed in glucocorticoid-treated male patients. This was an observational cohort study at Shimoshizu National Hospital in Japan. Analyzed were 161 male patients newly treated with high-dose glucocorticoid (≥20 mg/day prednisolone equivalent) (initial age: 53.5±16.9, initial glucocorticoid dose: 38.9±12.9 mg/day (0.66±0.23 mg/kg/day), follow-up time: 70.4±52.5 months) and 33 male patients with no glucocorticoid (initial age: 52.7±13.0, follow-up time: 76.4±62.7 months). The vertebral fracture was determined by x-rays. Symptomatic vertebral fractures occurred more frequently in the high-dose glucocorticoid group (21.1%) than in the no glucocorticoid group (3.0%). Using Cox model, the adjusted hazard ratio (HR) for the high-dose glucocorticoid group was 8.16 (95% confidence interval: 1.09-60.86) relative to the no glucocorticoid control group. In the high-dose glucocorticoid group, Kaplan-Meier analyses demonstrated that the incidence of fractures in the patients with glucocorticoid dose increase was significantly higher in comparison with those with no glucocorticoid dose increase. Cox model demonstrated that the risk was independently higher in every 10-year increment of initial age with HR 1.58 (1.18-2.13), in every 10 mg increment of initial dose of prednisolone with HR 2.03 (1.43-2.88), in every dose increase of glucocorticoid increase with HR 3.63 (2.04-6.46), and with each 1-gram decrease of cumulative dose of glucocorticoid with HR 0.88 (0.84-0.93). In male patients, high-dose glucocorticoid causes a significantly high prevalence of symptomatic vertebral fractures, and the independent risk factors are age, initial glucocorticoid dose, glucocorticoid dose increase, and decrease of cumulative glucocorticoid dose.

Short versus conventional term glucocorticoid therapy in acute exacerbation of chronic obstructive pulmonary disease - THe "REDUCE" trial

International guidelines advocate a 10 to 14-day course of systemic glucocorticoid therapy in the management of COPD exacerbations. The optimal duration of therapy is unknown and glucocorticoids have serious adverse effects. The aim of this trial is to demonstrate non-inferiority of a five-day compared to a 14-day course of systemic glucocorticoids with respect to COPD outcome, thereby significantly reducing steroid exposure and side effects in patients with COPD exacerbations. This is a randomised, placebo-controlled, non-inferiority multicentre trial. Patients with acute COPD exacerbation are randomised to receive 40 mg of prednisone-equivalent daily for 14 days (conventional arm) or glucocorticoid treatment for 5 days, followed by placebo for another 9 days (intervention arm). Follow-up is 180 days. The primary endpoint is time to next exacerbation. Secondary endpoints include cumulative glucocorticoid dose, time to open-label glucocorticoid therapy, glucocorticoid-associated side effects and complications, duration of hospital stay, death, change in FEV1, need for assisted ventilation, clinical outcome assessed by standardised questionnaires, and suppression of the hypothalamic-pituitary-adrenal axis. Mean age (± SD) of patients who finished the study was 70 ± 11 years. 12% had mild or moderate disease, whereas severe and very severe stages were found in 30 and 58%, respectively. At the time of inclusion, 20% of patients were under treatment with systemic glucocorticoids. If the strategy of significantly reducing cumulative exposure to glucocorticoids while taking advantage of their beneficial short-term effects proves to be successful, it will warrant a change in common glucocorticoid prescription practice, thereby improving the management of COPD.

Serum RANKL, osteoprotegerin (OPG), and RANKL/OPG ratio in nephrotic children

Receptor activator of NF-kB ligand (RANKL) and osteoprotegerin (OPG) play key roles in the pathogenesis of glucocorticoid-induced osteoporosis (GIO). The aim of our study was to determine whether the cumulative glucocorticoid dose (CGCS) in children with idiopathic nephrotic syndrome (INS) has any effect on the concentration of serum RANKL and OPG and the RANKL/OPG ratio. The study population consisted of 90 children with INS, aged 3–20 years, who were treated with GCS. These children were divided into two groups according to the CGCS: low (L) <1 g/kg body weight (BW) and high (H) ≥1 g/kg BW, respectively. The control group (C) consisted of 70 healthy children. RANKL concentration was observed to be significantly higher and OPG significantly lower in INS children than in the reference group: 0.21 (range 0.01–1.36) versus 0.15 (0–1.42) pmol/l (p < 0.05), respectively, and 3.76 (1.01–7.25) versus 3.92 (2.39–10.23) pmol/l (p < 0.05), respectively. The RANKL/OPG ratio was significantly higher in INS children (p < 0.01). The concentration of RANKL, similar to the RANKL/OPG ratio, was significantly higher in Group H children than in Group L children: 0.46 (0.02–1.36 ) versus 0.19 (0.01–1.25) (p < 0.01) and 0.14 (0.01–0.71) versus 0.05 (0.002–0.37) (p < 0.01), respectively. The concentration of OPG was similar in both groups. There was a positive correlation between CGCS and the concentration of sRANKL as well as the RANKL/OPG ratio (in both cases r = 0.33, p < 0.05). Based on these results, we suggest that long-term exposure to GCS results in a dose-dependent increase in serum RANKL concentration and the RANKL/OPG ratio, but not in the level of serum OPG.

Incidence of symptomatic vertebral fractures in women of childbearing age newly treated with high-dose glucocorticoid

The treatment and prevention of glucocorticoid (GC)-induced osteoporosis have been controversial in premenopausal women during their childbearing years. This study assessed the incidence and risk factors for symptomatic vertebral fracture in women of childbearing age newly treated with high-dose GC. An observational cohort study was conducted at the rheumatic center of Shimoshizu National Hospital in Chiba, Japan, from 1986 to 2006. The prevalence of symptomatic vertebral fractures, as determined by x-rays, was assessed in premenopausal (aged <50 years) women with collagen vascular disease newly treated with high-dose GC (> or =20 mg/d prednisolone equivalent) compared with their counterparts who did not receive GC. Differences in the incidences of vertebral fractures were compared between groups by the Kaplan-Meier method and evaluated by the log-rank test. Hazard ratios (HRs) with 95% CIs were estimated using the Cox proportional hazards regression model. A total of 373 women were assessed: 292 patients in the high-dose GC treatment group (mean [SD] initial age, 32.4 [8.2] years; initial dose, 43.8 [14.9] mg/d; follow-up time, 124.2 [75.4] months) and 81 patients in the non-GC control group (initial age, 39.3 [7.8] years; follow-up time, 106.5 [79.7] months). Symptomatic vertebral fractures occurred more frequently in the high-dose GC group (11.3%) than in the non-GC group (1.2%). Using the Cox model, the adjusted HR for the high-dose GC group was 13.96 (95% CI, 1.87-104.22) relative to the non-GC group. In the high-dose GC group, Kaplan-Meier analyses revealed that the incidence of fractures in women in their forties was significantly higher in comparison with those in their twenties (P < 0.001) and thirties (P < 0.05), and that the incidence of fractures in those who consumed alcohol (>80 g/wk of pure alcohol) was significantly higher than in those who did not (P < 0.05). The Cox model also revealed that the risk was independently higher with every 10-year increment of initial age (HR = 2.27; 95% CI, 1.46-3.53), with every GC dose increase (HR = 2.28; 95% CI, 1.58-3.31), and with each 1-gram decrease of cumulative GC dose (HR = 0.95; 95% CI, 0.93-0.98). In this study, high-dose GC use was associated with a significantly high prevalence of symptomatic vertebral fractures in premenopausal women with collagen vascular disease during their childbearing years. However, the fracture risk was relatively low in women of childbearing age, especially those in their twenties and thirties during the early years of treatment.

Is there a relationship between glucocorticoid (GC) dose and performance on functional outcome measures?

6542 Background: Functional tests are often used to assess the severity of weakness and fatigue experienced by patients undergoing GC therapy. The relationship between GC dosage and performance on these tests is unknown. We aim to determine the strength of association between these sets of variables. Methods: We retrospectively reviewed the medical records of 34 sub-acute stem cell transplant (allogeneic) patients treated with GCs to determine their cumulative GC dosage between transplant and physical therapy (PT) initial evaluation, number of days of GC exposure and average daily dosage. Outcomes on 3 functional measures were collected at PT initial evaluation, including the 6 min walk test (ft), 50 ft walk time (sec) and repeated sit to stand (sec, S-T-S). The institutional review board approved this study. Central tendency data were calculated. The strength of correlation between GC dosage and scores on three functional outcome measures was determined using regression analysis. Results: These patients (20 males; 50.5 ± 12.87 yrs old) received a median cumulative GC dose of 2,106 mg (range 195-4486 mg) over a median duration of GC exposure of 22 days (range 5-60 days) for a median daily GC exposure of 82.1 mg/day (range 24.6-140.9). Modest correlations existed between 1) cumulative dose and 50 ft walk time (r = 0.3677) and repeated S-T-S time (r = 0.3154), 2) duration and 50 ft walk time (r = 0.3781) and 3) average daily dose and repeated S-T-S time (r = 0.3269). Other correlations were poor, ranging from r = -0.1534 to r = 0.2010. Conclusions: GC dosage has minimal to no relationship with outcomes on functional tests intended to measure strength and endurance. Other assessments such as isolated strength testing of key muscles may be necessary to more accurately reflect the severity of muscle weakness and concomitant disability associated with GC treatment. No significant financial relationships to disclose.

Prevalent vertebral fractures among children initiating glucocorticoid therapy for the treatment of rheumatic disorders

Vertebral fractures are an under-recognized problem in children with inflammatory disorders. We studied spine health among 134 children (87 girls) with rheumatic conditions (median age 10 years) within 30 days of initiating glucocorticoid therapy. Children were categorized as follows: juvenile dermatomyositis (n = 30), juvenile idiopathic arthritis (n = 28), systemic lupus erythematosus and related conditions (n = 26), systemic arthritis (n = 22), systemic vasculitis (n = 16), and other conditions (n = 12). Thoracolumbar spine radiograph and dual x-ray absorptiometry for lumbar spine (L-spine) areal bone mineral density (BMD) were performed within 30 days of glucocorticoid initiation. Genant semiquantitative grading was used for vertebral morphometry. Second metacarpal morphometry was carried out on a hand radiograph. Clinical factors including disease and physical activity, calcium and vitamin D intake, cumulative glucocorticoid dose, underlying diagnosis, L-spine BMD Z score, and back pain were analyzed for association with vertebral fracture. Thirteen vertebral fractures were noted in 9 children (7%). Of these, 6 patients had a single vertebral fracture and 3 had 2-3 fractures. Fractures were clustered in the mid-thoracic region (69%). Three vertebral fractures (23%) were moderate (grade 2); the others were mild (grade 1). For the entire cohort, mean +/- SD L-spine BMD Z score was significantly different from zero (-0.55 +/- 1.2, P < 0.001) despite a mean height Z score that was similar to the healthy average (0.02 +/- 1.0, P = 0.825). Back pain was highly associated with increased odds for fracture (odds ratio 10.6 [95% confidence interval 2.1-53.8], P = 0.004). In pediatric rheumatic conditions, vertebral fractures can be present prior to prolonged glucocorticoid exposure.

Bone Health Should Be an Important Concern in the Care of Patients Affected by 21 Hydroxylase Deficiency

Osteoporosis has been an understandable concern for children and adult patients with congenital adrenal hyperplasia (CAH) who may receive or have received supraphysiological doses of glucocorticoids. Some previous reports on bone mineral density (BMD) in adult CAH patients showed no significant differences in BMD between patients with CAH and controls, but others have found lower BMD in CAH patients. In reports documenting the BMD reduction, this outcome has been attributed to an accumulated effect of prolonged exposure to excess glucocorticoids during infancy and childhood. We recently conducted a trial to establish the role of the total cumulative glucocorticoid dose on BMD. We established for the first time that there was a negative relationship between total cumulative glucocorticoid dose and lumbar and femoral BMD. Women might benefit from the preserving effect of estrogens compared to men. BMI (Body Mass Index) also appeared to protect patients from bone loss. In light of this, physicians should bear in mind the potential consequences of glucocorticoids on bone and therefore adjust the treatment and improve clinical and biological surveillance from infancy. Furthermore, preventive measures against corticosteroid-induced osteoporosis should be discussed right from the beginning of glucocorticoid therapy.

A rational use of glucocorticoids in patients with early arthritis has a minimal impact on bone mass

IntroductionGlucocorticoid (GC)-induced osteoporosis is a frequent complication in patients with rheumatoid arthritis. However, little information exists about the consequences of GC use in patients with early arthritis. Here we describe the variables underlying the use of GC in early arthritis, as well as its effect on bone-mineral density.MethodsData from 116 patients in our early arthritis register were analyzed (90 women; median age, 52.5 years, interquartile range (IQR, 38.5-66); 6-month median disease duration at entry (IQR, 4-9)). In this register, the clinical and treatment information was recorded systematically, including the cumulative GC dose. Lumbar spine, hip, and forearm bone-mineral density (BMD) measurements were performed at entry and after a 2-year follow-up. A multivariate analysis was performed to establish the variables associated with the use of GCs, as well as those associated with variations in BMD.ResultsOf the patients with early arthritis studied, 67% received GCs during the 2-year follow-up. GCs were more frequently prescribed to elderly patients, those with higher basal disease activity and disability, and patients with positive rheumatoid factor. When adjusted for these variables, GCs were less frequently prescribed to female patients. The use of GCs was associated with an increase of BMD in the ultradistal region of the forearm, although it induced a significant loss of BMD in the medial region of the forearm. No relevant effect of GC was noted on the BMD measured at other locations.ConclusionsThe frequent use of GCs as a "bridge therapy" in patients with early arthritis does not seem to be associated with relevant loss of bone mass. Moreover, cumulative GC administration might be associated with an increase of juxtaarticular BMD.

Treatment of Polymyalgia Rheumatica

Polymyalgia rheumatica (PMR) treatment is based on low-dose glucocorticoids. Glucocorticoid-sparing agents have also been tested. Our objective was to systematically examine the peer-reviewed literature on PMR therapy, particularly the optimal glucocorticoid type, starting doses, and subsequent reduction regimens as well as glucocorticoid-sparing medications. We searched Cochrane Databases and MEDLINE (1957 through December 2008) for English-language articles on PMR treatment (randomized trials, prospective cohorts, case-control trials, and case series) that included 20 or more patients. All data on study design, PMR definition criteria, medical therapy, and disease outcomes were collected using a standardized protocol. Thirty studies (13 randomized trials and 17 observational studies) were analyzed. No meta-analyses or systematic reviews were found. The PMR definition criteria, treatment protocols, and outcome measures differed widely among the trials. Starting prednisone doses higher than 10 mg/d were associated with fewer relapses and shorter therapy than were lower doses; starting prednisone doses of 15 mg/d or lower were associated with lower cumulative glucocorticoid doses than were higher starting prednisone doses; and starting prednisone doses higher than 15 mg/d were associated with more glucocorticoid-related adverse effects. Slow prednisone dose tapering (<1 mg/mo) was associated with fewer relapses and more frequent glucocorticoid treatment cessation than faster tapering regimens. Initial addition of oral or intramuscular methotrexate provided efficacy at doses of 10 mg/wk or higher. Infliximab was ineffective as initial cotreatment. The scarcity of randomized trials and the high level of heterogeneity of studies on PMR therapy do not allow firm conclusions to be drawn. However, PMR remission seems to be achieved with prednisone treatment at a dose of 15 mg/d in most patients, and reductions below 10 mg/d should preferably follow a tapering rate of less than 1 mg/mo. Methotrexate seems to exert glucocorticoid-sparing properties.