Glucocorticoids inhaled, fracture risk

In a retrospective cohort comparison of patients using inhaled glucocorticoids or bronchodilators with controls, there was an increased risk of fractures, particularly at the hip and spine, in those using inhaled glucocorticoids. There were no differences in relative fracture risks... 

Accelerated bone loss, with an increased risk of first hip fracture, occurred in elderly women taking oral glucocorticoids (201). At baseline, 122 (1.5%) women were taking inhaled glucocorticoids only (median dose equivalent to... 

While biochemical markers of bone metabolism may be sensitive to the effects of glucocorticoids in the short term, the relation between changes in these markers and intermediate measures, such as bone mineral density, and the more important clinical outcomes of fractures, is unknown. In a random stratified sample of 3222 women in the perimenopausal age range (47-56 years), including 119 women with asthma, bone mineral density was measured to determine whether asthma was a risk factor of osteoporosis and to investigate the effect of inhaled glucocorticoids (102). The subjects had predominantly adult-onset asthma, as the age at diagnosis was over 40 years. There were 26 patients who were treated mainly with... 

It can be hypothesized that different glucocorticoids have different systemic effects, and therefore different effects on bone metabolism. An alternative hypothesis is that these effects are dose dependent (85), support for which comes from a population-based case-control study of 16 341 older patients with hip fractures (mean age 79 years) and 29 889 controls recent use of an inhaled glucocorticoid was associated with a small dose-dependent increase in the risk of hip fracture (120). 

Estimates of the important outcome of bone fracture have shown a small increased risk with inhaled glucocorticoids, but this may well be a feature of the disease rather than the therapy, because comparisons with treatment with bronchodilator drugs show no difference between risk factors in patients taking glucocorticoids or bronchodilators. 

Adults Previous observational data have suggested that inhaled glucocorticoids reduce bone mineral density and increase the risk of fractures (SEDA-31, 307 SEDA-32, 313). An analysis of a subset of 685 patients using inhaled glucocorticoids in the TORCH study, and excluding patients taking oral... 

In a meta-analysis of 13 observational and randomized controlled trials there was no overall increased risk of fractures associated with inhaled glucocorticoids (RR = 1.02 Cl = 0.96, 1.08) even when the analysis was restricted to the four randomized controlled trials [24 ]. However when stratified by the dose of inhaled glucocorticoid there was a small increased risk of fractures amongst those taking high doses (RR = 1.30 Cl = 1.07,1.58). 

In contrast, another meta-analysis of three double-blind randomized controlled triak, including TORCH, in a total of 8131 patients, showed no increased risk of fractures (OR = 1.09 Cl = 0.89, 1.33) despite the use of high-dose inhaled glucocorticoids (beclomethasone 800 micrograms, fluticasone 1000 micrograms)... 

In a more recent review of the literature, including trial and observational data, the authors concluded that inhaled glucocorticoids may produce a modest reduction in bone mineral density and a small associated increase in the risk of fracture, which appears to be dose-related [22 ]. However, it has been argued that most of this evidence comes from observational data, with risks of bias (recall and confounding) and that adequately powered randomized controlled trials are needed to clarify this risk and quantify it accurately [25 ]. In the meantime, physicians need to be aware of this potential adverse effect, and, certainly in the case of asthma, try to maintain patients on the lowest dose of inhaled glucocorticoids required to control their disease. 

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