Inhaled corticosteroids and the risk of fracture in chronic obstructive pulmonary disease (original) (raw)
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Dose-response relationship for risk of non-vertebral fracture with inhaled corticosteroids
Clinical and Experimental Allergy, 2008
Objective To determine the strength of association between the dose of inhaled corticosteroids (ICS) and risk of non-vertebral fracture in adults.Methods A systematic review and meta-analysis of case–control studies of non-vertebral fractures in adults, in which at least two doses of ICS were reported as the dose of beclomethasone dipropionate (BDP) or equivalent.Results Five case–control studies were identified, with a total of 43 783 cases and 259 936 controls. There was an association between the risk of non-vertebral fracture and increasing dose of BDP. The random-effects odds ratio of relative risk for a non-vertebral fracture was 1.12 (95% confidence interval 1.00–1.26) per 1000 μg increase in the daily dose of BDP or equivalent.Conclusion In older adults, the relative risk of non-vertebral fractures increases by about 12% for each 1000 μg/day increase in the dose of BDP or equivalent. The magnitude of this risk was considerably less than other common risk factors for fracture in the older adult.
Long-term Use of Inhaled Corticosteroids in COPD and the Risk of Fracture
Chest, 2017
and by financial support from Novartis Pharmaceuticals Canada Inc. Dr Gonzalez is the recipient of an FRQS chercheur-boursier clinicien award. Dr. Suissa is the recipient of the James McGill Professorship award. Acknowledgements: The authors thank the Commission d'accès à l'information du Québec for allowing access to the data and the Régie de l'assurance maladie du Québec (RAMQ) for providing the database.
Are inhaled corticosteroids associated with an increased risk of fracture in children?
Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA, 2004
Inhaled corticosteroids are widely used in the long-term management of asthma in children. Data on the relationship between inhaled corticosteroid therapy and osteoporotic fracture are inconsistent. We address this issue in a large population-based cohort of children aged 4-17 years in the UK (the General Practice Research Database). The incidence rates of fracture among children aged 4-17 years taking inhaled corticosteroids (n=97,387), taking bronchodilators only (n=70 984) and a reference group (n=345,758) were estimated. Each child with a non-vertebral fracture (n=23,984) was subsequently matched by age, sex, practice, and calendar time to one child without a fracture. Fracture incidence was increased in children using inhaled corticosteroids, as well as in those receiving bronchodilators alone. With an average daily beclomethasone dose of 200 microg or less, the crude fracture risk relative to nonusers was 1.10 [95% confidence interval (CI), 0.96-1.26]; with dosage of 201-400 m...
Thorax, 2011
Background The effect of inhaled corticosteroids (ICS) on fracture risk in patients with chronic obstructive pulmonary disease (COPD) remains uncertain. The aim of this study was to evaluate the association between ICS and fractures in COPD. Methods MEDLINE, EMBASE, regulatory documents and company registries were searched up to August 2010. Randomised controlled trials (RCTs) of budesonide or fluticasone versus control treatment for COPD ($24 weeks duration) and controlled observational studies reporting on fracture risk with ICS exposure vs no exposure in COPD were included. Peto OR meta-analysis was used for fracture risk from RCTs while ORs from observational studies were pooled using the fixed effect inverse variance method. Doseeresponse analysis was conducted using varianceweighted least squares regression in the observational studies. Heterogeneity was assessed using the I 2 statistic. Results Sixteen RCTs (14 fluticasone, 2 budesonide) with 17 513 participants, and seven observational studies (n¼69 000 participants) were included in the meta-analysis. ICSs were associated with a significantly increased risk of fractures (Peto OR 1.27; 95% CI 1.01 to 1.58; p¼0.04; I 2 ¼0%) in the RCTs. In the observational studies, ICS exposure was associated with a significantly increased risk of fractures (OR 1.21; 95% CI 1.12 to 1.32; p<0.001; I 2 ¼37%), with each 500 mg increase in beclomethasone dose equivalents associated with a 9% increased risk of fractures, OR 1.09 (95% CI 1.06 to 1.12; p<0.001). Conclusion Among patients with COPD, long-term exposure to fluticasone and budesonide is consistently associated with a modest but statistically significant increased likelihood of fractures.
A Meta-Analysis of Prior Corticosteroid Use and Fracture Risk
Journal of Bone and Mineral Research, 2004
The relationship between use of corticosteroids and fracture risk was estimated in a metaanalysis of data from seven cohort studies of ϳ42,000 men and women. Current and past use of corticosteroids was an important predictor of fracture risk that was independent of prior fracture and BMD.
International Journal of Chronic Obstructive Pulmonary Disease
Patients with chronic obstructive pulmonary disease (COPD) demonstrate a greater osteoporosis prevalence than the general population. This osteoporosis risk may be enhanced by treatment with inhaled corticosteroids (ICSs), which are recommended for COPD management when combined with long-acting bronchodilators, but may also be associated with reduced bone mineral density (BMD). We conducted a narrative literature review reporting results of randomized controlled trials (RCTs) of an ICS versus placebo over a treatment period of at least 12 months, with the aim of providing further insight into the link between bone fractures and ICS therapy. As of 16 October 2017, we identified 17 RCTs for inclusion. The ICSs studied were budesonide (six studies), fluticasone propionate (five studies), mometasone furoate (three studies), beclomethasone dipropionate, triamcinolone acetonide, and fluticasone furoate (one each). We found no difference in the number of bone fractures among patients receiving ICSs versus placebo across the six identified RCTs reporting fracture data. BMD data were available for subsets of patients in few studies, and baseline BMD data were rare; where these data were given, they were reported for treatment groups without stratification for factors known to affect BMD. Risk factors for reduced BMD and fractures, such as smoking and physical activity, were also often not reported. Furthermore, a standardized definition of the term "fracture" was not employed across these studies. The exact relationship between long-term ICS use and bone fracture incidence in patients with stable COPD remains unclear in light of our review. We have, however, identified several limiting factors in existing studies that may form the basis of future RCTs designed specifically to explore this relationship.
Calcified Tissue International, 2008
We conducted a case-control study on fracture risk associated with the use of orally administered prednisolone/prednisone, budesonide, methylprednisolone, and hydrocortisone to assess if the various preparations were associated with different fracture patterns. Cases were all subjects with any fracture sustained during the year 2000 (n = 124,655). For each case, three controls (n = 373,962) matched on age and gender were randomly drawn from the background population. Adjustments were made for concurrent diseases, use of other drugs, and a number of other factors. Oral prednisolone/prednisone was associated with a dose-dependent increase in fracture risk starting from a dose of around 6.7 mg/day. Oral budesonide was not associated with an increase in overall fracture risk, but the doses in general were low (\3 mg/day). Oral hydrocortisone was not associated with overall risk of fractures. Oral methylprednisolone was only used intermittently and was not associated with an increase in overall fracture risk at the low doses used. After termination of oral prednisolone/prednisone, it took more than 1 year for fracture risk to return to the levels of the background population. Oral prednisolone is associated with a dose-dependent increase in overall fracture risk. Budesonide at low doses did not seem to be associated with fracture risk. Hydrocortisone was not associated with an increase in the risk of fractures. It may take a year from last use of prednisolone/prednisone before fracture risk returns to that of the general population.
Inhaled Corticosteroids and Bone Health
The Open Respiratory Medicine Journal, 2014
Inhaled corticosteroids (ICS) are the cornerstones in the management of bronchial asthma and some cases of chronic obstructive pulmonary disease. Although ICS are claimed to have low side effect profiles, at high doses they can cause systemic adverse effects including bone diseases such as osteopenia, osteoporosis and osteonecrosis. Corticosteroids have detrimental effects on function and survival of osteoblasts and osteocytes, and with the prolongation of osteoclast survival, induce metabolic bone disease. Glucocorticoid-induced osteoporosis (GIO) can be associated with major complications such as vertebral and neck of femur fractures. The American College of Rheumatology (ACR) published criteria in 2010 for the management of GIO. ACR recommends bisphosphonates along with calcium and vitamin D supplements as the first-line agents for GIO management. ACR recommendations can be applied to manage patients on ICS with a high risk of developing metabolic bone disease. This review outlines the mechanisms and management of ICS-induced bone disease.
Inhaled glucocorticoids are associated with vertebral fractures in COPD patients
Journal of bone and mineral metabolism, 2017
Chronic obstructive pulmonary disease (COPD) is an independent risk factor for osteoporosis. Oral glucocorticoids are deleterious to bone; however, the impact of inhaled glucocorticoids (ICS) remains unclear. Our objective was to determine whether ICS contribute to osteoporosis and fragility fractures. Sixty-one COPD patients, 35 current users of ICS and 26 who had never received glucocorticoids, were evaluated for bone mineral density (BMD) and body composition and underwent vertebral fracture assessment (VFA). The risk factors for bone disease considered for analysis were age, gender, ICS use, body mass index (BMI), muscle mass index (MMI), and the Global Initiative for Chronic Obstructive Lung Disease (GOLD) category. The Fracture Risk Assessment Tool (FRAX) calculation tool for the Brazilian population was also employed. The groups did not differ regarding gender, BMI, MMI, GOLD class, lowest values of the BMD T-score and Z-score, prevalence of osteoporosis, or low BMD for age. ...