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1.
Rheumatol Int ; 35(8): 1325-33, 2015 Aug.
Article in English | MEDLINE | ID: mdl-25724472

ABSTRACT

Glucocorticoids (GC) are widely used in rheumatoid arthritis (RA). Ongoing active disease due to GC resistance may unfavorably influence long-term disease outcome in RA. We studied the association between the presence of glucocorticoid receptor (GR) and glucocorticoid-induced transcript 1 (GLCCI1) gene polymorphisms, which modulate GC sensitivity, and baseline disease activity score (DAS) and efficacy of GC bridging therapy in RA. We prospectively studied in vivo GC sensitivity in 138 patients with recent-onset or longstanding RA. In vivo GC sensitivity was expressed as the relative decrease in DAS following 2 weeks of standardized GC therapy. All patients were genotyped for the GR polymorphisms BclI (rs41423247), N363S (rs6195), 9ß (rs6198), ER22/23EK (rs6189 + rs6190), and the GLCCI1 variant rs37972 and subsequently divided in groups carrying a polymorphism associated with increased GC sensitivity (BclI-G allele, N363S-G allele, GLCCI1-C allele) or decreased GC sensitivity (9ß-G allele, ER22/23EK-A/A allele, GLCCI1-T allele). Differences in baseline DAS and relative decrease in DAS in the different genotype groups were analyzed using analysis of covariance and linear regression. Baseline DAS was higher in patients who carried polymorphisms of the GR and GLCCI1 genes associated with decreased GC sensitivity. GLCCI1 genotype, but not GR genotypes, was associated with improvement in DAS in male patients with RA. The GLCCI1 gene minor allele (rs37972) may be associated with less efficient GC bridging therapy in male RA patients. Carriers of the BclI-G, N363S-G, or GLCCI1-C alleles had lower levels of baseline disease activity, suggesting a role for the GLCCI1 and GR gene in regulation of GC sensitivity to endogenously produced cortisol.


Subject(s)
Arthritis, Rheumatoid/genetics , Receptors, Glucocorticoid/genetics , Adult , Aged , Arthritis, Rheumatoid/drug therapy , Cohort Studies , Female , Glucocorticoids/therapeutic use , Haplotypes , Humans , Male , Middle Aged , Severity of Illness Index , Treatment Outcome
2.
Neth J Med ; 72(10): 528-32, 2014 Dec.
Article in English | MEDLINE | ID: mdl-26219758

ABSTRACT

OBJECTIVE: Androgen deprivation therapy (ADT) puts patients at an increased risk of developing osteoporosis. Assessment of bone mineral density (BMD) is most commonly performed by dual energy X-ray absorptiometry (DXA). Alternative ways of estimating BMD, such as quantitative ultrasound (QUS) measurement of the heel, are explored as DXA is expensive, non-portable and uses ionising radiation. We therefore investigated the diagnostic value of QUS as compared with DXA in patients commencing ADT. METHODS: In this cross-sectional study of 60 patients with prostate cancer who were about to start ADT, BMD was measured with DXA and QUS. The fracture risk score, as implemented by the Dutch National Osteoporosis Guideline, was also measured. RESULTS: No significant correlations were found between the separate DXA T scores and worst DXA T score, and the QUS T scores. Correlations between DXA T scores/QUS scores and fracture risk score were also non-significant. If QUS had been used as a screening tool, with a threshold of T ≤ -0.5 to perform DXA, then relevant osteopenia/osteoporosis (worst DXA T score ≤ -2.0) would have been missed in 1/18 (5.6%) patients. The negative predictive value is 0.95. Using QUS as a screening test prior to DXA and a QUS threshold T score ≤ -0.5 would avoid 21 (35%) DXA scans at the cost of missing one (5.6%) case. CONCLUSION: QUS testing cannot replace DXA scans fully as a diagnostic test. However, QUS can be incorporated as triage test prior to DXA to reduce the need for unnecessary DXA scans and the associated costs.


Subject(s)
Absorptiometry, Photon , Bone Density , Heel/diagnostic imaging , Osteoporosis/diagnosis , Absorptiometry, Photon/methods , Absorptiometry, Photon/standards , Aged , Androgen Antagonists/adverse effects , Androgen Antagonists/therapeutic use , Bone Density/physiology , Cross-Sectional Studies , Humans , Male , Middle Aged , Osteoporosis/etiology , Prostatic Neoplasms/drug therapy , Risk Factors , Sensitivity and Specificity , Triage , Ultrasonography
3.
Osteoporos Int ; 25(2): 701-9, 2014 Feb.
Article in English | MEDLINE | ID: mdl-24030287

ABSTRACT

UNLABELLED: The response rate to the invitation to the fracture liaison service and reasons for non-response were evaluated in 2,207 fragility fracture patients. Fifty-one percent responded; non-responders were most often not interested (38 %) or were hip fracture patients. After 1 year of treatment, 88 % was still persistent and 2 % had a new fracture. INTRODUCTION: To increase the percentage of elderly fracture patients undergoing a dual energy x-ray absorptiometry (DXA) measurement, and to investigate why some patients did not respond to invitation to our fracture liaison service (FLS). METHODS: In four Dutch hospitals, fracture patients ≥ 50 years were invited through a written or personal invitation at the surgical outpatient department, for a DXA measurement and visit to our FLS. Patients who did not respond were contacted by telephone. In patients diagnosed with osteoporosis, treatment was started. Patients were contacted every 3 months during 1 year to assess drug persistence and the occurrence of subsequent fractures. RESULTS: Of the 2,207 patients who were invited, 50.6 % responded. Most frequent reasons for not responding included: not interested (38 %), already screened/under treatment for osteoporosis (15.7 %), physically unable to attend the clinic (11.5 %), and death (5.2 %). Hip fracture patients responded less frequently (29 %) while patients with a wrist (60 %) or ankle fracture (65.2 %) were more likely to visit the clinic. In 337 responding patients, osteoporosis was diagnosed and treatment was initiated. After 12 months of follow-up, 88 % of the patients were still persistent with anti-osteoporosis therapy and only 2 % suffered a subsequent clinical fracture. CONCLUSION: In elderly fracture patients, the use of a FLS leads to an increased response rate, a high persistence to drug treatment, and a low rate of subsequent clinical fractures. Additional programs for hip fracture patients are required, as these patients have a low response rate.


Subject(s)
Bone Density Conservation Agents/therapeutic use , Osteoporotic Fractures/prevention & control , Preventive Health Services/organization & administration , Absorptiometry, Photon/methods , Aged , Bone Density/drug effects , Female , Humans , Male , Mass Screening/organization & administration , Medication Adherence , Middle Aged , Netherlands/epidemiology , Osteoporosis/diagnosis , Osteoporosis/drug therapy , Osteoporosis/epidemiology , Osteoporotic Fractures/epidemiology , Osteoporotic Fractures/physiopathology , Outpatient Clinics, Hospital
4.
Osteoarthritis Cartilage ; 21(6): 823-30, 2013 Jun.
Article in English | MEDLINE | ID: mdl-23541875

ABSTRACT

OBJECTIVES: Age-related changes in articular cartilage are likely to play a role in the etiology of osteoarthritis (OA). One of the major age-related changes in cartilage is the accumulation of advanced glycation end products (AGEs). The present study evaluates whether pentosidine can predict radiographic progression and/or burden over 5 years follow-up in a cohort of early knee and/or hip OA. DESIGN: The 5 years follow-up data of 300 patients from cohort hip & cohort knee (CHECK) were used. Radiographic progression and burden were assessed by X-rays of both knees and hips (Kellgren and Lawrence (K&L) and Altman scores). Baseline pentosidine levels (and urinary CTXII as a comparator) were measured by high-performance-liquid-chromatography (HPLC) and enzyme linked immunosorbent assay (ELISA). Univariable and multivariable associations including baseline radiographic damage, age, gender, body mass index (BMI) and kidney function were performed. RESULTS: Both pentosidine and urinary C-terminal telopeptide of type II collagen (uCTXII) correlated with radiographic progression and burden. In general pentosidine did not have an added predictive value to uCTXII for progression nor burden of the disease. The best prediction was obtained for burden of radiographic damage (R(2) = 0.60-0.88), bus this was predominantly determined by baseline radiographic damage (without this parameter R(2) = 0.07-0.17). Interestingly, pentosidine significantly added to prediction of osteophyte formation, whereas uCTXII significantly added to prediction of JSN in multivariable analysis. CONCLUSION: Pentosidine adds to prediction of radiographic progression and burden of osteophyte formation and uCTXII to radiographic progression and burden of JSN, but overall skin pentosidine did not perform better that uCTXII in predicting radiographic progression or burden. Burden of damage over 5 years is mainly determined by radiographic joint damage at baseline.


Subject(s)
Arginine/analogs & derivatives , Disease Progression , Lysine/analogs & derivatives , Osteoarthritis, Hip/metabolism , Osteoarthritis, Knee/metabolism , Skin/chemistry , Aged , Arginine/analysis , Chromatography, High Pressure Liquid , Collagen Type II/urine , Cross-Sectional Studies , Enzyme-Linked Immunosorbent Assay , Female , Follow-Up Studies , Humans , Lysine/analysis , Male , Middle Aged , Osteoarthritis, Hip/diagnostic imaging , Osteoarthritis, Knee/diagnostic imaging , Osteophyte/metabolism , Radiography
5.
Arthritis Rheum ; 64(10): 3095-101, 2012 Oct.
Article in English | MEDLINE | ID: mdl-22673898

ABSTRACT

OBJECTIVE: To optimize use of the Disease Activity Score in 28 joints (DAS28) in early rheumatoid arthritis (RA) by adding the "squeeze test" of forefeet. METHODS: The squeeze test is used to examine bilateral compression pain (BCP) across the metatarsophalangeal (MTP) joints. For this study, data for patients participating in the Treatment in the Rotterdam Early Arthritis Cohort study, an ongoing clinical trial that evaluates different induction therapies in patients with early RA, were randomly divided into 2 subsets. In subset 1 (149 patients and 819 disease activity assessments), the mathematical function of the DAS28-squeeze was constructed using a linear regression model with the DAS as the dependent variable and the DAS28 and squeeze test as the independent variables. A DAS28-BCP disease state was also constructed, in which DAS28 disease state categorizations were upgraded one state if the result of the squeeze test was positive. In subset 2 (153 patients and 754 assessments), concordance in disease states between the DAS28, DAS28-squeeze, and DAS28-BCP disease states was compared, using both the DAS and Boolean-defined remission criteria as reference. RESULTS: Agreement between the DAS and the DAS28-squeeze (82%) was significantly higher than agreement between the DAS and the DAS28 (76%). When we assessed the group of patients who had arthritis of the forefeet only (22 patients and 46 assessments), overall agreement between the DAS and the DAS28 was 40%, while agreement between the DAS and the DAS28-squeeze was 59% and that between the DAS and the DAS28-BCP disease state was 65%. Furthermore, the specificities of the DAS28-squeeze and the DAS28-BCP (80% and 81%, respectively) were higher than that of the DAS28 (76%), while the sensitivities of the DAS28, DAS28-squeeze, and DAS28-BCP to identify true remission according to the Boolean criteria were 88%, 87%, and 81%, respectively. CONCLUSION: Adding the squeeze test of forefeet to the DAS28 has value for dependably classifying the disease state in patients with early RA.


Subject(s)
Arthritis, Rheumatoid/diagnosis , Metatarsophalangeal Joint/physiopathology , Arthritis, Rheumatoid/physiopathology , Cohort Studies , Female , Humans , Male , Middle Aged , Sensitivity and Specificity , Severity of Illness Index
6.
Osteoarthritis Cartilage ; 20(8): 846-53, 2012 Aug.
Article in English | MEDLINE | ID: mdl-22595228

ABSTRACT

OBJECTIVE: Adipose tissue is an endocrine tissue releasing adipokines suggested to be involved in the pathogenesis of osteoarthritis (OA). Nevertheless, their relative contribution and exact mechanisms are still ambiguous. The aim of this study is to compare serum adipokine levels between end-stage knee OA patients and controls and to relate these serum levels to local parameters of cartilage damage and synovial inflammation. METHODS: Serum was collected from 172 severe knee OA patients, shortly before total knee replacement (TKR) surgery and from 132 controls without radiographic knee OA [Kellgren & Lawrence (K&L) = 0]. Serum adiponectin, leptin, and resistin levels were measured by enzyme-linked immunosorbent assay (ELISA). Cartilage and synovial tissue were collected at TKR surgery and assessed for cartilage degeneration and synovial inflammation by histochemistry and biochemical analyses. RESULTS: The adipokine levels were all distinctly higher in OA patients as compared to controls. Especially adiponectin and leptin were associated with female gender (stand beta = 0.239 and 0.467, respectively, P < 0.001) and body mass index (BMI) (stand beta = -0.189 and 0.396, respectively, P < 0.001). No associations between serum levels of adipokines and cartilage damage (histochemistry, proteoglycan content) were found whereas weak but positive associations with synovial inflammation were found [adiponectin and interleukin-1ß (IL-1ß), stand beta = 0.172, P = 0.02; resistin and histology, stand beta = 0.183, P = 0.034, adjusted for demographics]. CONCLUSION: This study suggests an important involvement of adipokines in OA patients considering their high serum levels compared to controls. Associations of systemic adipokines with local synovial tissue inflammation were found, although not represented by similar relations with cartilage damage, suggesting that adipokines are of relevance in the inflammatory component of OA.


Subject(s)
Adipokines/blood , Cartilage, Articular/pathology , Osteoarthritis, Knee/blood , Adiponectin/blood , Aged , Aged, 80 and over , Arthroplasty, Replacement, Knee , Body Mass Index , Case-Control Studies , Enzyme-Linked Immunosorbent Assay , Female , Humans , Interleukin-1beta/blood , Leptin/blood , Male , Middle Aged , Proteoglycans/blood , Resistin/blood , Synovial Fluid/chemistry
7.
Osteoarthritis Cartilage ; 20(3): 233-40, 2012 Mar.
Article in English | MEDLINE | ID: mdl-22227209

ABSTRACT

OBJECTIVES: Age is the most prominent predisposition for development of osteoarthritis (OA). Age-related changes of articular cartilage are likely to play a role. Advanced glycation endproducts (AGEs) accumulate in cartilage matrix with increasing age and adversely affect the biomechanical properties of the cartilage matrix and influence chondrocyte activity. In clinical studies AGEing of cartilage and its relation to actual cartilage damage can only be measured by surrogate markers (e.g., serum, skin or urine AGE levels and imaging or biochemical markers of cartilage damage). In this study actual cartilage AGE levels were directly related to actual cartilage damage by use of cartilage obtained at joint replacement surgery. METHODS: Cartilage and urine samples were obtained from 69 patients undergoing total knee replacement. Samples were analyzed for pentosidine as marker of AGE. Cartilage damage was evaluated macroscopically, histologically, and biochemically. RESULTS: Cartilage and urine pentosidine both increased with increasing age. The higher the macroscopic, histological, and biochemical cartilage damage the lower the cartilage pentosidine levels were. In multiple regression analysis age is not found to be a confounder. CONCLUSION: There is an inverse relation between cartilage AGEs and actual cartilage damage in end-stage OA. This is likely due to ongoing (ineffective) increased turnover of cartilage matrix proteins even in end stage disease.


Subject(s)
Arginine/analogs & derivatives , Cartilage, Articular/metabolism , Lysine/analogs & derivatives , Osteoarthritis, Knee/metabolism , Aged , Aging/metabolism , Arginine/metabolism , Arginine/urine , Arthroplasty, Replacement, Knee , Biomarkers/metabolism , Biomarkers/urine , Cartilage, Articular/pathology , Collagen/metabolism , Female , Glycation End Products, Advanced/metabolism , Glycation End Products, Advanced/urine , Humans , Knee Joint/metabolism , Knee Joint/pathology , Lysine/metabolism , Lysine/urine , Male , Middle Aged , Osteoarthritis, Knee/pathology , Osteoarthritis, Knee/surgery , Severity of Illness Index
8.
Eur J Clin Microbiol Infect Dis ; 30(7): 903-8, 2011 Jul.
Article in English | MEDLINE | ID: mdl-21293900

ABSTRACT

The treatment of choice of H. pylori infections is a 7-day triple-therapy with a proton pump inhibitor (PPI) plus amoxicillin and either clarithromycin or metronidazole, depending on local antibiotic resistance rates. The data on efficacy of eradication therapy in a group of rheumatology patients on long-term NSAID therapy are reported here. This study was part of a nationwide, multicenter RCT that took place in 2000-2002 in the Netherlands. Patients who tested positive for H. pylori IgG antibodies were included and randomly assigned to either eradication PPI-triple therapy or placebo. After completion, follow-up at 3 months was done by endoscopy and biopsies were sent for culture and histology. In the eradication group 13% (20/152, 95% CI 9-20%) and in the placebo group 79% (123/155, 95% CI 72-85%) of the patients were H. pylori positive by histology or culture. H. pylori was successfully eradicated in 91% of the patients who were fully compliant to therapy, compared to 50% of those who were not (difference of 41%; 95% CI 18-63%). Resistance percentages found in isolates of the placebo group were: 4% to clarithromycin, 19% to metronidazole, 1% to amoxicillin and 2% to tetracycline.


Subject(s)
Anti-Bacterial Agents/administration & dosage , Helicobacter Infections/drug therapy , Proton Pump Inhibitors/administration & dosage , Rheumatic Diseases/complications , Adult , Aged , Aged, 80 and over , Antibodies, Bacterial/blood , Biopsy , Endoscopy, Gastrointestinal , Female , Helicobacter Infections/diagnosis , Helicobacter pylori/isolation & purification , Histocytochemistry , Humans , Immunoglobulin G/blood , Male , Middle Aged , Netherlands , Placebos/administration & dosage , Serology/methods , Treatment Outcome
9.
Osteoarthritis Cartilage ; 18(10): 1329-36, 2010 Oct.
Article in English | MEDLINE | ID: mdl-20673850

ABSTRACT

OBJECTIVES: Age-related changes in articular cartilage are likely to play a role in the aetiology of osteoarthritis (OA). One of the major age-related changes in cartilage is the accumulation of advanced-glycation-endproducts (AGEs). Since, cartilage tissue is not readily available from patients for studying AGE levels, alternative approaches such as analyzing skin and urine are needed to study the role of cartilage AGE levels in OA. METHODS: Paired human skin and cartilage samples were obtained post mortem. Paired skin and urine samples were obtained from the CHECK cohort (early OA patients). Pentosidine levels were measured by high-performance liquid chromatography (HPLC). As marker of cumulative cartilage damage X-rays of both knees and hips were scored. Urinary CTXII (uCTXII) levels were measured, to assess current cartilage breakdown. RESULTS: Cartilage and skin pentosidine correlate well (R=0.473, P=0.05). Skin pentosidine was higher in mild (summed (Kellgren & Lawrence K&L) over four large joints ≥4) compared to no (summed K&L≤3) radiographic OA (P=0.007). Urinary pentosidine was not different between these two groups. Skin pentosidine levels were not related to cartilage breakdown (highest vs lowest tertile of uCTXII). Urinary pentosidine, however, was higher in the highest compared to the lowest uCTXII tertile (P=0.009). Multiple regression analysis showed age to be the only predictor of the summed K&L score and age, creatinine clearance and urinary pentosidine as predictors of uCTXII. CONCLUSION: The higher skin and urinary pentosidine levels in those with mild compared to no radiographic joint damage and low vs high cartilage breakdown respectively suggest that AGEs may contribute to disease susceptibility and/or progression. However, relations are weak and cannot be used as surrogate markers of severity of OA.


Subject(s)
Arginine/analogs & derivatives , Lysine/analogs & derivatives , Osteoarthritis, Hip/metabolism , Osteoarthritis, Knee/metabolism , Skin/chemistry , Adult , Aged , Arginine/analysis , Arginine/urine , Biomarkers/analysis , Biomarkers/urine , Cartilage, Articular/chemistry , Cohort Studies , Collagen Type II/urine , Female , Humans , Lysine/analysis , Lysine/urine , Male , Middle Aged , Osteoarthritis, Hip/diagnostic imaging , Osteoarthritis, Hip/urine , Osteoarthritis, Knee/diagnostic imaging , Osteoarthritis, Knee/urine , Radiography , Severity of Illness Index
10.
Osteoarthritis Cartilage ; 17(4): 482-8, 2009 Apr.
Article in English | MEDLINE | ID: mdl-18926729

ABSTRACT

OBJECTIVE: Recent in vitro studies showed that celecoxib, a selective cyclooxygenase (COX)-2 inhibitor, protects human osteoarthritic cartilage tissue from degeneration. The objective was to substantiate these beneficial effects in an in vivo (clinical) study with celecoxib treatment of patients with severe knee osteoarthritis (OA) and subsequent evaluation of cartilage tissue ex vivo. METHODS: Patients with knee OA were treated 4 weeks prior to total knee replacement surgery with either celecoxib 200mg b.d., indomethacin 50mg b.d., or received no treatment. During surgery cartilage and synovium were collected and analyzed in detail ex vivo. RESULTS: When compared to non-treated patients, patients treated with celecoxib showed significant beneficial effects on proteoglycan synthesis, -release, and -content, confirming the in vitro data. In the indomethacin group, no significant differences were found compared to the control group. On the contrary, a tendency towards a lower content and lower synthesis rate was found. In the treated groups prostaglandin-E(2) levels were lower than in the control group, indicating COX-2 inhibition. Ex vivo release of interleukin-1 beta (IL-1 beta) and tumour necrosis factor-alpha by synovial tissue was decreased by treatment with celecoxib, whereas in the indomethacin group only IL-1 beta release was decreased. CONCLUSION: Using this novel approach we were able to demonstrate an in vivo generated chondrobeneficial effect of celecoxib in patients with end stage knee OA.


Subject(s)
Cartilage, Articular/drug effects , Cyclooxygenase 2 Inhibitors/therapeutic use , Osteoarthritis, Knee/drug therapy , Aged , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Arthroplasty, Replacement, Knee , Cartilage, Articular/metabolism , Cartilage, Articular/pathology , Celecoxib , Dinoprostone/biosynthesis , Female , Humans , Indomethacin/therapeutic use , Interleukin-1beta/metabolism , Male , Matrix Metalloproteinases/metabolism , Middle Aged , Nitric Oxide/biosynthesis , Osteoarthritis, Knee/metabolism , Osteoarthritis, Knee/pathology , Osteoarthritis, Knee/surgery , Proteoglycans/metabolism , Pyrazoles/therapeutic use , Sulfonamides/therapeutic use , Synovial Membrane/drug effects , Synovial Membrane/metabolism , Tumor Necrosis Factor-alpha/metabolism
11.
Ned Tijdschr Geneeskd ; 151(21): 1178-85, 2007 May 26.
Article in Dutch | MEDLINE | ID: mdl-17557758

ABSTRACT

OBJECTIVE: To compare the effects of alendronate and alfacalcidol in the prevention ofglucocorticoid-related osteoporosis in patients with a rheumatic disease. DESIGN: Randomised, double-blind, double-placebo clinical trial (www. clinicaltrials.gov; number: NCT00138983). METHODS: A total of 201 patients with rheumatic disease who were starting glucocorticoid treatment at a daily dose that was equivalent to at least 7.5 mg of prednisone were randomised to alendronate (10 mg) and a placebo capsule ofalfacalcidol daily (n = 100) or alfacalcidol (1 microg) and a placebo tablet ofalendronate daily (n = 101) for 18 months. Primary outcome was change in lumbar spine bone mineral density at 18 months. The main secondary outcome was the incidence of morphometrically confirmed vertebral deformities. RESULTS: Overall, 163 patients completed the study. The bone mineral density of the lumbar spine increased by 2.1% (95% CI: 1.1-3.1) in the alendronate group and decreased by 1.9% (95% CI: -3.I--0.7) in the alfacalcidol group. At 18 months the mean difference in change in bone mineral density between the two groups was 4.0% (95% CI: 2.4-5-5). Three patients in the alendronate group had a new vertebral deformity, compared with 8 patients in the alfacalcidol group, including 5 symptomatic vertebral fractures in 3 patients; the hazard ratio was 0.4 (95% CI: 0.1-1.4). CONCLUSION: Alendronate was more effective than alfacalcidol in preventing glucocorticoid-induced bone loss during this 18-month trial in patients with rheumatic diseases who were starting glucocorticoid treatment.

12.
Ned Tijdschr Geneeskd ; 150(9): 476-80, 2006 Mar 04.
Article in Dutch | MEDLINE | ID: mdl-16553045

ABSTRACT

Two mechanisms of the genomic action ofglucocorticoids (GCs) can be distinguished: transrepression, yielding mainly an anti-inflammatory effect, and transactivation, resulting mainly in metabolic-endocrine side effects. Selective glucocorticoid receptor agonists (SEGRAs) cause selective transrepression, yielding the same anti-inflammatory effect as GCs, but with fewer side effects. NO is bound to several drugs to increase their effect; in nitrosteroids, NO is coupled to GC, resulting in a synergistic anti-inflammatory effect. Drug targeting can be achieved with GCs by incorporation of GC into polyethyleneglycol(PEG)-liposomes, resulting in very high concentrations ofGCs at the site of inflammation. Well-designed studies are needed to determine the place of SEGRAs, nitrosteroids and liposomal GCs in clinical practice.


Subject(s)
Anti-Inflammatory Agents/therapeutic use , Glucocorticoids/therapeutic use , Receptors, Glucocorticoid/agonists , Transcriptional Activation , Anti-Inflammatory Agents/adverse effects , Drug Synergism , Glucocorticoids/adverse effects , Humans , Nitric Oxide/metabolism
13.
Ned Tijdschr Geneeskd ; 149(4): 196-200, 2005 Jan 22.
Article in Dutch | MEDLINE | ID: mdl-15702739

ABSTRACT

Four patients with arthritis appeared to have this as a consequence of an internal disorder: a 60-year-old woman and a 20-year-old man with diabetes mellitus and arthritis of an ankle had Charcot arthropathy, whilst a 53-year-old woman and a 60-year-old man with polyarthritis had previously undiagnosed haemochromatosis. Patients were then adequately treated. Charcot arthropathy and haemochromatosis are not uncommon. Early diagnosis is important with respect to preventive and therapeutic measures. In patients with Charcot arthropathy immobilisation allows healing of the fractures. Bisphosphonates may be given in order to decrease bone resorption. In patients with haemochromatosis therapeutic bleeding may limit further damage to the joints and to the internal organs.


Subject(s)
Arthritis/etiology , Arthropathy, Neurogenic/complications , Diabetes Complications , Hemochromatosis/complications , Adult , Arthritis/diagnosis , Arthritis/drug therapy , Arthropathy, Neurogenic/diagnosis , Arthropathy, Neurogenic/drug therapy , Diagnosis, Differential , Diphosphonates/therapeutic use , Female , Fracture Healing , Hemochromatosis/diagnosis , Hemochromatosis/drug therapy , Humans , Male , Middle Aged
15.
Clin Exp Rheumatol ; 21(2): 217-20, 2003.
Article in English | MEDLINE | ID: mdl-12747278

ABSTRACT

OBJECTIVE: Low or medium dose prednisone in early rheumatoid arthritis (RA), albeit with significant variation in clinical efficacy, reduces the progression of joint damage. The glucocorticoid receptor (GR) number in peripheral mononuclear cells (PBMC) might be helpful to predict which patients will respond to low or medium dose prednisone and therefore do not or will not need higher doses. With this in mind we determined in a double blind, placebo controlled study at baseline and yearly the GR number in PBMC. METHODS: Eighty-one early RA patients (disease duration less than one year) were included. All patients fulfilled the ACR criteria and were disease modifying antirheumatic drugs (DMARD) and glucocorticoid-naive. They were randomly assigned to treatment with 10 mg prednisone daily or placebo. From all patients disease activity (CRP, number of tender and swollen joints), the radiological joint score, bone mineral density, and the GR number in PBMC were measured annually. RESULTS: In females the GR number was up-regulated over time in both the prednisone and the placebo group. The same trend was observed in males. No correlations were found between the GR number in the prednisone users at the start of their treatment and changes in radiological scores or bone density after 2 years of treatment. No correlations were found between the GR number at the start and the clinical characteristics after a follow-up of 2 years. CONCLUSION: The GR number in the PBMC of early RA patients did not predict which patients would be prednisone responders based on clinical or radiological parameters. However, the up-regulation of the GR number in PBMC in early RA patients towards the GR number of healthy subjects during the first two years of their disease course seems to reflect a recovery or compensatory mechanism as a response to an ongoing inflammatory process. This recovery may be not enough to efficiently control the inflammatory situation.


Subject(s)
Anti-Inflammatory Agents/therapeutic use , Arthritis, Rheumatoid/drug therapy , Arthritis, Rheumatoid/immunology , Prednisone/therapeutic use , Receptors, Glucocorticoid/immunology , Up-Regulation/immunology , Adult , Aged , Anti-Inflammatory Agents/immunology , Double-Blind Method , Female , Humans , Leukocytes, Mononuclear/immunology , Male , Middle Aged , Predictive Value of Tests , Prednisone/immunology
16.
Clin Exp Rheumatol ; 20(4): 463-8, 2002.
Article in English | MEDLINE | ID: mdl-12175100

ABSTRACT

OBJECTIVE: In patients with rheumatoid arthritis (RA) of longer duration, glucocorticoid receptor (GR) down-regulation has been reported without any change in cortisol levels. This phenomenon might play a role in the aetio-pathogenesis of RA. Therefore we studied GR expression, as well as the serum cortisol levels, in patients with recently diagnosed RA. METHODS: In 81 early diagnosed RA patients with disease duration < 1 year (52F/29M; mean (SD) age 63 (13) years) and in 39 age and sex matched controls (23F/16M; mean age 63 (15) years) blood samples were taken between 8-10 h AM. GR expression (GR-number and GR-affinity), serum cortisol levels, ESR, CRP, painful and swollen joints were measured. RESULTS: A significantly lower GR-number was found in the female patients compared with female controls: 7.0 versus 9.8fmol/million cells, respectively (difference: 2.8, 95% CI 1.1 - 4.6). Interestingly, also serum cortisol levels were significantly lower in the female patients compared with the female controls: 0.21 versus 0.41 micromol/l, respectively (difference: 0.20, 95% CI 0.12 - 0.28). However, between the male patients and male controls no difference was found in GR expression nor in serum cortisol levels. Neither in female nor in male patients were correlations found between GR expression and parameters of disease activity nor was there a relation between GR expression and serum cortisol levels. CONCLUSIONS: Changes in GR expression as well as serum cortisol were not a general phenomenon in early diagnosed RA patients, being present only in females and not related to disease activity. Therefore it seems unlikely that GR expression per se is causally involved in the pathogenesis of RA. We cannot preclude that it may be involved in the incidence, severity and course of RA, as this may be differentially regulated in males and females.


Subject(s)
Arthritis, Rheumatoid/metabolism , Receptors, Glucocorticoid/metabolism , Adult , Aged , Aged, 80 and over , Arthritis, Rheumatoid/pathology , Blood Sedimentation , C-Reactive Protein/analysis , Down-Regulation , Female , Humans , Hydrocortisone/blood , Male , Middle Aged , Outpatients , Pain , Severity of Illness Index
17.
Rheumatology (Oxford) ; 40(12): 1375-83, 2001 Dec.
Article in English | MEDLINE | ID: mdl-11752508

ABSTRACT

OBJECTIVE: This study was designed to determine whether the prevalence of vertebral deformities in patients with rheumatoid arthritis (RA) treated with corticosteroids (Cs) is higher than in RA patients not receiving Cs therapy. PATIENTS AND METHODS: This multicentre cross-sectional study included 205 patients with RA who were receiving Cs orally on a daily basis and 205 patients with RA who did not receive Cs, matched for sex and age. Vertebral deformities were scored according to the Kleerekoper method. RESULTS: Vertebral deformities were found in 52 (25%) patients on Cs and in 26 (13%) patients not on Cs. Sixteen (8%) patients in the group on Cs had experienced clinical manifestations of an acute vertebral fracture in the past vs only three patients (1.5%) among those not on Cs. The use of Cs tended to increase the risk of developing a vertebral deformity [adjusted odds ratio (OR) 1.56, 95% confidence interval (CI) 0.81-2.99] and symptomatic vertebral fracture (adjusted OR 1.42, 95% CI 0.24-8.32). Each 1-mg increase in the current daily Cs dose increased the risk of a vertebral deformity (adjusted OR 1.05, 95% CI 0.98-1.13) and of a symptomatic vertebral fracture (adjusted OR 1.05, 95% CI 0.89-1.24). CONCLUSION: There is a higher prevalence of vertebral deformities and clinical manifestations of vertebral fractures in patients on Cs than in those not on Cs. Our data indicate that the use of Cs and each 1-mg increase in the current daily Cs dose may increase the risk of development of a vertebral deformity and symptomatic vertebral fracture in patients with RA.


Subject(s)
Arthritis, Rheumatoid/epidemiology , Glucocorticoids/adverse effects , Prednisolone/adverse effects , Spinal Fractures/epidemiology , Spine/pathology , Aged , Arthritis, Rheumatoid/drug therapy , Arthritis, Rheumatoid/pathology , Cross-Sectional Studies , Female , Glucocorticoids/administration & dosage , Humans , Male , Middle Aged , Prednisolone/administration & dosage , Prevalence , Risk Factors , Spinal Fractures/pathology
18.
J Rheumatol ; 28(11): 2535-9, 2001 Nov.
Article in English | MEDLINE | ID: mdl-11708429

ABSTRACT

OBJECTIVE: Many patients with systemic lupus erythematosus (SLE) and fibromyalgia (FM) may spend less time exposed to the sun than healthy individuals and thus might have low vitamin D levels. It is known that hydroxychloroquine (HCQ) inhibits conversion of 25(OH)- to 1,25(OH)2-vitamin D both in vitro and in patients with sarcoidosis. We assessed winter serum 25(OH)- and 1,25(OH)2-vitamin D levels in patients with SLE and FM. METHODS: We recruited 25 consecutive female SLE and 25 female FM patients in London, Ontario, between January and March 2000. Subjects completed a brief questionnaire. Serum levels of 25(OH)-, 1,25(OH)2-vitamin D, and parathyroid hormone (PTH) were measured. RESULTS: In SLE patients mean 25(OH)-vitamin D was 46.5 nmol/l and mean 1,25(OH)2-vitamin D was 74.4 pmol/l. In FM patients these means were 51.5 nmol/l and 90.1 pmol/l, respectively. Serum 25(OH)-vitamin D levels did not significantly differ between SLE and FM patients, nor after adjusting for age and vitamin D, milk consumption, and sun block use. In 14 of the SLE patients and 12 of the FM patients 25(OH)-vitamin D levels < 50 nmol/l were found. SLE patients not using vitamin D supplements had lower 25(OH)-vitamin D levels than those who did. 1,25(OH)2-vitamin D tended to be lower in the SLE compared to the FM patients. This difference could be attributed to HCQ use: HCQ users (n = 17) had lower 1,25(OH)2-vitamin D levels than nonusers (n = 33); the mean adjusted difference was 24.4 pmol/l (95% CI 2.8-49.9). CONCLUSION: Half the SLE and FM patients had 25(OH)-vitamin D levels < 50 nmol/l, a level at which PTH stimulation occurs. Our data suggest that in SLE patients HCQ might inhibit conversion of 25(OH)-vitamin D to 1,25(OH)2-vitamin D.


Subject(s)
Fibromyalgia/blood , Lupus Erythematosus, Systemic/blood , Vitamin D/analogs & derivatives , Adolescent , Adult , Aged , Dietary Supplements , Drug Antagonism , Female , Fibromyalgia/drug therapy , Humans , Hydroxychloroquine/metabolism , Hydroxychloroquine/therapeutic use , Immunosuppressive Agents/metabolism , Immunosuppressive Agents/therapeutic use , Lupus Erythematosus, Systemic/drug therapy , Middle Aged , Parathyroid Hormone/blood , Pilot Projects , Seasons , Surveys and Questionnaires , Vitamin D/administration & dosage , Vitamin D/blood , Vitamin D/metabolism
19.
Ned Tijdschr Geneeskd ; 143(14): 719-25, 1999 Apr 03.
Article in Dutch | MEDLINE | ID: mdl-10347626

ABSTRACT

Paget's disease of bone affects one or more bones and is characterized by increased bone turnover (remodelling) with hypertrophy and abnormal bone structure with diminished strength leading to deformity and fracture. The cause of the disease is not known, possibly is a slow virus infection. For diagnosis and follow-up the conventional bone markers, serum alkaline phosphatase and urine hydroxyproline, are still useful. Paget's disease cannot be cured, but it may be suppressed. Specific drug treatment aims at reducing the increased bone remodelling. New and potent biphosphonates enable early and more effective treatment of Paget's disease than in the past and better prevention of late complications of the disease.


Subject(s)
Osteitis Deformans/diagnosis , Osteitis Deformans/therapy , Adult , Aged , Alkaline Phosphatase/blood , Arthralgia/drug therapy , Arthralgia/etiology , Arthroplasty, Replacement , Calcium/therapeutic use , Diphosphonates/therapeutic use , Female , Follow-Up Studies , Fractures, Bone/etiology , Fractures, Bone/surgery , Genetic Predisposition to Disease , Hearing Loss/etiology , Humans , Hydroxyproline/urine , Male , Middle Aged , Osteitis Deformans/complications , Virus Diseases/complications , Vitamin D/therapeutic use
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