RESUMO
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.
Assuntos
Conservadores da Densidade Óssea/uso terapêutico , Densidade Óssea/efeitos dos fármacos , Glucocorticoides/efeitos adversos , Osteoporose/induzido quimicamente , Osso e Ossos/efeitos dos fármacos , Feminino , Fraturas Ósseas/induzido quimicamente , Fraturas Ósseas/prevenção & controle , Humanos , Masculino , Osteoporose/economia , Osteoporose/prevenção & controleRESUMO
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.
Assuntos
Eosinofilia/diagnóstico , Fasciite/diagnóstico , Glucocorticoides/uso terapêutico , Contratura/diagnóstico , Contratura/etiologia , Contratura/patologia , Eosinofilia/tratamento farmacológico , Eosinofilia/patologia , Fasciite/tratamento farmacológico , Fasciite/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pele/patologia , Fatores de Tempo , Resultado do TratamentoRESUMO
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.
RESUMO
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.