A Cochrane review [Abstract] 1 included 7 studies with a total of 1989 subjects. The male:female ratio was 2:1. The patients were generally less than 60 years old. There was no evidence of increased risk of loss of bone mineral density or fractures. There was no significant chance in osteocalcin at conventional doses of inhaled steroids (SMD -0.34, 95% CI -0.72 to 0.04), although a statistically significant change was seen in those studies using experimental doses of inhaled steroid in excess of the doses recommended by the Britis Thoracic Society (SMD 0.97, 95% CI -1.61 to -0.34).
A study 2 included a cohort of 1 671 subjects with a diagnosis of asthma or COPD (mean age 80.6 years). Cox regression analysis was used to determine the dose-response relationship between inhaled corticosteroid (ICS) exposure and time to first fracture.During a mean follow-up period of 9.4 years, 982 patients (59%) received a prescription for an inhaled corticosteroid and 187 patients had a fracture. After adjusting for the effects of age and gender, a dose-related increase in fracture risk with exposure to inhaled corticosteroids (rate ratio for mean daily dose > 601 μg, 2.53, 95% CI 1.65 to 3.89; overall trend p < 0.0001) was found. The results were similar after adjusting for oral corticosteroid exposure, airflow obstruction diagnosis, historical fracture, and bronchodilator use (RR 4.21, 95% CI, 2.19 to 8.13), and also in the subset of people with no exposure to oral corticosteroids (RR 4.54, 95% CI, 1.23 to 16.74).
The Quebec health-care databases were used to form a cohort of patients with COPD over 1990 to 2005, followed until 2007 for the first hip or upper extremity fracture 3, and a nested case-control analysis was performed.In the cohort of 240 110 subjects, there were 19 396 subjects with fractures during a mean 5.3 years (15.2 per 1 000 per year). Any use of ICSs was not associated with an increased rate of fracture, but the fracture rate was increased with > 4 years of ICS use at daily doses ≥ 1 000 μg in fluticasone equivalents (RR 1.10, 95% CI 1.02 to 1.19). This risk increase did not differ between men and women.
A systematic review and meta-analysis 4 included 16 RCTs (14 fluticasone, 2 budesonide) with a total of 17 513 subjects, and 7 observational studies with a total of 69 000 subjects. ICSs were associated with a significantly increased risk of fractures (Peto OR 1.27, 95% CI 1.01 to 1.58) 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), with each 500 μg increase in beclomethasone dose equivalents associated with a 9% increased risk of fractures (OR 1.09, 95% CI 1.06 to 1.12).
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