Risk of fractures with inhaled corticosteroids in COPD: systematic review and meta-analysis of randomised controlled trials and observational studies (original) (raw)
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Inhaled corticosteroids and the risk of fracture in chronic obstructive pulmonary disease
Qjm-an International Journal of Medicine, 2007
Background: Inhaled corticosteroids are used increasingly to treat people with COPD, but the extent to which these drugs increase the risk of fracture is unclear. Aim: To quantify the dose-response relationship between fracture risk and inhaled corticosteroids in people with COPD, independent of the effects of percent predicted FEV 1 and oral corticosteroids. Design: Nested case-control study. Methods: Cases and controls were COPD patients aged 540 years or more at diagnosis, with a FEV 1 measurement recorded in The Health Improvement Network database, up to 5 July 2005. Cases (people with a fracture event after 1 January 1998, n ¼ 1235) were assigned up to four controls (n ¼ 4598), matched by gender and general practice. Results: Mean FEV 1 was 57.5% in cases, and 58.5% in controls. Inhaled corticosteroids had been prescribed in 69% of cases (median dose 269 mcg/day) and 66% (226 mcg/day) of controls. Oral corticosteroids had been prescribed in 60% of cases (median annual prescription rate 0.6) and 56% of controls (also 0.6 per year). Risk of fracture increased with increasing mean daily doses of inhaled corticosteroid (p for trend 0.007), and was most marked in those whose daily dose was 51600 mcg (OR 1.80, 95% CI 1.04-3.11). This effect was virtually unchanged by adjustment for mean percent predicted FEV 1 and annual prescription rate for oral corticosteroids (OR for highest dose exposure 1.74, 95% CI 1.00-3.01). Discussion: Our findings add to the evidence that the use of inhaled corticosteroids is associated with a small increase in fracture risk, particularly at higher doses.
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.
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.
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.
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...
Fracture prevention in COPD patients; a clinical 5-step approach
Respiratory research, 2015
Although osteoporosis and its related fractures are common in patients with COPD, patients at high risk of fracture are poorly identified, and consequently, undertreated. Since there are no fracture prevention guidelines available that focus on COPD patients, we developed a clinical approach to improve the identification and treatment of COPD patients at high risk of fracture. We organised a round-table discussion with 8 clinical experts in the field of COPD and fracture prevention in the Netherlands in December 2013. The clinical experts presented a review of the literature on COPD, osteoporosis and fracture prevention. Based on the Dutch fracture prevention guideline, they developed a 5-step clinical approach for fracture prevention in COPD. Thereby, they took into account both classical risk factors for fracture (low body mass index, older age, personal and family history of fracture, immobility, smoking, alcohol intake, use of glucocorticoids and increased fall risk) and COPD-sp...
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. ...
Long-term therapy in COPD: any evidence of adverse effect on bone?
International Journal of Chronic Obstructive Pulmonary Disease, 2009
Patients with COPD have high risk for osteoporosis and fractures. Hip and vertebral fractures might impair mobility, and vertebral fractures further reduce lung function. This review discusses the evidence of bone loss due to medical treatment opposed to disease severity and risk factors for COPD, and therapeutic options for the prevention and treatment of osteoporosis in these patients. A review of the English-language literature was conducted using the MEDLINE database until June 2009. Currently used bronchodilators probably lack adverse effect on bone. Oral corticosteroids (OCS) increase bone resorption and decrease bone formation in a dose response relationship, but the fracture risk is increased more than reflected by bone densitometry. Inhaled corticosteroids (ICS) have been associated with both increased bone loss and fracture risk. This might be a result of confounding by disease severity, but high doses of ICS have similar effects as equipotent doses of OCS. The lifestyle factors should be modified, use of regular OCS avoided and use of ICS restricted to those with evidenced effect and probably kept at moderate doses. The health care should actively reveal risk factors, include bone densitometry in fracture risk evaluation, and give adequate prevention and treatment for osteoporosis.
Clinical Therapeutics, 2010
Background: According to evidence-based guidelines, the combination of inhaled corticosteroids and inhaled long-acting β 2-agonists in a single inhaler is recommended for patients with chronic obstructive pulmonary disease (COPD) who are experiencing exacerbations. The relative effectiveness of combination products such as budesonide/ formoterol (BUD/FM) and fluticasone propionate/ salmeterol (FP/SM) has not been well documented. Objective: This study was conducted to investigate the different outcomes associated with the use of either BUD/ FM or FP/SM in a single inhaler in patients with COPD. Outcomes included rates of exacerbations, emergency department (ED) visits and hospitalizations for COPD, medication utilization, and treatment adherence. Methods: A 1-year, population-based, matched cohort study was conducted using administrative health care databases from the Canadian province of Quebec. Patients treated with BUD/FM were matched (1:1) to patients treated with FP/SM based on the following criteria: age group, sex, calendar year of treatment initiation, the number of COPD exacerbations in the year before treatment initiation, and use of inhaled shortacting β 2-agonists (SABAs) and ipratropium bromide in the 3 months before treatment initiation. COPD exacerbations were defined as a claim for a short-course (≤14 days) prescription of oral corticosteroids, or an ED visit or a hospitalization for COPD. Events occurring within 15 days were counted as a single exacerbation. Between-group comparisons of the number of exacerbations, ED visits, and hospitalizations for COPD, as well as claims for oral corticosteroids, were performed using Poisson regression models. Between-group comparisons of the mean number of doses of SABAs and ipratropium bromide per day were performed using linear regression models. Treatment adherence was also assessed. Results: Of the 2262 patients in the matched cohort, 78.1% were aged ≥65 years and 52.1% were men. COPD exacerbations, claims for oral corticosteroids, use of SABAs, and patient adherence to treatment did not differ significantly between the BUD/FM and FP/ SM groups. However, the BUD/FM group was significantly less likely to have an ED visit (adjusted relative risk [RR] = 0.75; 95% CI, 0.58 to 0.97) or hospitalization (adjusted RR = 0.61; 95% CI, 0.47 to 0.81) for COPD and had fewer claims for prescriptions for tiotropium (adjusted RR = 0.71; 95% CI, 0.57 to 0.89). The BUD/FM group also used fewer doses of ipratroprium bromide than the FP/SM group (adjusted mean difference,-0.2 dose; 95% CI,-0.3 to-0.1). Conclusions: These COPD patients treated with BUD/ FM were less likely to have ED visits and hospitalizations for COPD and used fewer doses of anticholinergic medication than patients treated with FP/SM in the year after treatment initiation. However, due to the observational nature of the study design, we cannot conclude with certainty that the medication was the only factor