[Eosinophilic fasciitis; the importance of early detection for optimal outcomes]. / Eosinofiele fasciitis, het belang van een tijdige herkenning voor de genezing.

Eosinophilic fasciitis (EF) is a disease with unknown aetiology, although an immunologic pathogenesis is suspected. The characteristic features of this inflammatory disease include scleroderma-like skin indurations, predominantly on the extremities, and peripheral blood eosinophilia. Internal organs are generally not affected. Initiation of systemic glucocorticoid therapy at an early stage results in a good response and remission of symptoms. This is illustrated in 3 cases of EF to demonstrate the importance of early detection in this disease.

Glucocorticoid-induced osteoporosis: a review on pathophysiology and treatment options.

Glucocorticoids, often regarded as ancient drugs, are still frequently used in modern medicine because of their strong anti-inflammatory and immunosuppressive properties. Nowadays, the side effects of glucocorticoids are well-known and physicians often anticipate on these side effects. Bone loss is one of the most important side effects of glucocorticoid use, even in low doses. The main effect of glucocorticoids on bone is inhibition of osteoblast function, leading to a decrease in bone formation. Also nongenomic effects (mediated by glucocorticoid interactions with biological membranes, either through binding to membrane receptors or by physicochemical interactions) may have a role in the pathogenesis of glucocorticoid-induced osteoporosis. Several studies and reports show a decrease in bone mineral density and an increased risk of fractures during glucocorticoid use. Prior and current exposure to glucocorticoids increases the risk of fractures beyond that explained by values of bone mineral density. This discrepancy could be explained by osteocyte apoptosis leading to rapid weakening of bone architecture and increase in fractures risk. Bone loss starts promptly after initiation of glucocorticoids and is mainly taking place in the first six months of treatment. Bone loss is predominantly found in bone with a high trabecular content, like vertebrae. The risk of glucocorticoid-induced osteoporosis can be reduced by general measurements like prescribing glucocorticoids in a low dose and for a short period of time. Furthermore, pharmacological intervention for prevention of glucocorticoid-induced osteoporosis is needed depending on glucocorticoid dose, expected duration of glucocorticoid treatment, age and gender of the patient and sometimes bone mineral density at start of the glucocorticoid treatment. Bisphosphonates seem to be the first choice of pharmacological intervention for prevention and treatment of glucocorticoid-induced osteoporosis and are cost-effective in subgroups of patients (depending on age, gender, glucocorticoid dose and fracture history). There is no evidence that one specific bisphosphonate is superior to another bisphosphonate due to lacking of head-to-head studies on glucocorticoid-induced osteoporosis. A recent study showed that alendronate is superior to alfacalcidol in prevention of glucocorticoid-induced osteoporosis in patients starting glucocorticoids of 7.5 mg or more on a daily basis. Calcium and plain vitamin D3 supplementation are considered as important support for prevention and treatment of glucocorticoid-induced osteoporosis. Despite the increased knowledge on bone loss and fracture risk during glucocorticoid use and the possibilities of pharmacological intervention of it, studies made clear that the care given by physicians in prevention and treatment of glucocorticoid-induced osteoporosis needs to be optimized in future years. Further training of health care workers in pathophysiology, general measurements and pharmacological intervention for prevention and treatment of glucocorticoid-induced osteoporosis, is needed.

[Alendronate more effective than alfacalcidol in the prevention of osteoporosis in patients with rheumatic disease who are starting glucocorticoid therapy]. / Alendroninezuur effectiever dan alfacalcidol voor preventie van osteoporose bij patiënten met een reumatische ziekte die starten met glucocorticoïdtherapie.

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.

Prevention and treatment of glucocorticoid-induced osteoporosis with active vitamin D3 analogues: a review with meta-analysis of randomized controlled trials including organ transplantation studies.

The aim of this review with meta-analysis was to determine if there is a rationale to use activated forms of vitamin D3 to treat or prevent glucocorticoid-induced osteoporosis, and to compare the effect of active vitamin D3 metabolites with that of other anti-osteoporosis therapies. We performed a systemic search using MEDLINE/PubMed (1966-2003). Animal studies and clinical trials involving humans with data on therapy to treat or prevent glucocorticoid-induced osteoporosis with active vitamin D3 analogues were included. Animal studies and basic research studies with active vitamin D3 were reviewed (qualitative review). Meta-analysis (quantitative review) on clinical trials (including organ transplantation studies) was performed with percent change in lumbar spine bone mineral density or bone mineral content as the primary outcome measure; the secondary outcome measure was incidence of vertebral fractures. Fifty-four articles were found. Animal and basic research studies showed that active vitamin D3 analogues can inhibit bone loss during treatment with glucocorticoids. Concerning the effect on bone mineral density, the pooled effect size of active vitamin D3 analogues compared with no treatment, placebo, plain vitamin D3 and/or calcium was 0.35 (95% confidence interval (CI) 0.18, 0.52). Compared with bisphosphonates, the pooled effect size was -1.03 (95% CI -1.71, -0.36). The pooled estimate of the relative risk for vertebral fractures of active vitamin D3 analogues compared with no treatment, placebo, plain vitamin D3 and/or calcium was 0.56 (95% CI 0.34, 0.92) and compared with bisphosphonates it was 1.20 (95% CI 0.32, 4.55). Active vitamin D3 analogues not only preserve bone during glucocorticoid therapy more effectively than no treatment, placebo, plain vitamin D3 and/or calcium, but are also more effective in decreasing the risk of vertebral fractures. Bisphosphonates, however, are more effective in preserving bone and decreasing the risk of vertebral fractures than active vitamin D3 analogues.

Prevalence of vertebral deformities and symptomatic vertebral fractures in corticosteroid treated patients with rheumatoid arthritis.

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.