Decreased BMD appeared to be largely under detected, even among our control subjects. A high percentage of control subjects were found to have osteopenia/osteoporosis, which would have otherwise gone undetected if not for their participation in this study. Similarly, it was through the National Osteoporosis Risk Assessment in the US that of 200,160 postmenopausal women (which included 1912 Asians), 39.6% were found to have osteopenia and 7% with osteoporosis.[13
] A study conducted in Malaysia reported a prevalence of osteoporosis of 24.1% in 514 disease-free, uterus-intact non-hormone replacement therapy-using women.[13
For any meaningful analysis of the effects of ICS on BMD, a detailed evaluation of the baseline characteristics of the asthmatic group and the control group was essential to reduce bias during analysis. Although the number of female patients in our control group was higher than in the asthmatic group , the difference in male to female ratio was not statistically significant between the two groups. All other characteristics were also matched between the two groups except for PAI, which was higher in the control group. One would expect a higher BMD among subjects who are more physically active, but this increase in the level of activity did not result in a significant difference in the T-scores of the control subjects compared with the asthmatic patients. The PAI value depended largely on the accuracy of the patient's historical recall of physical activities conducted in an “average day.” Furthermore, the larger PAI IQR in the asthmatic patients suggests that the values obtained skewed toward the extremes. Although gender, genetic background (i.e., family history), cigarette smoking, alcohol consumption, and menopausal status are believed to be among the important factors influencing BMD,[14
] our results suggested that these factors did not significantly affect the BMD of our study subjects. However, the number of patients recruited into our study who actually had a history of ever-smoking, alcohol consumption, or a family history of osteoporosis was small.
Not surprisingly, the older asthmatic patients in this study had lower BMD compared with younger patients, while patients with higher BMI had higher BMD compared to patients with lower BMI. This observation has also been reported by other studies such as the one conducted by Burger et al
] who reported that the BMD yearly rate of change increased and decreased with advancing age and BMI, respectively.
The results of our study suggest that the duration of asthma, asthma control, cumulative budesonide dose-years, and rescue oral prednisolone did not significantly affect the risk of osteopenia and osteoporosis among patients with bronchial asthma. The cumulative budesonide-years used in our study is the product of the mean daily equipotent dose of inhaled budesonide and the number of years on ICS; representative of the cumulative dose of ICS described in other studies, such as the one conducted by Toogood et al
Although several studies have shown that ICS either decrease or did not significantly affect BMD,[9
] the study of 69 patients reported by Toogood et al
] showed a higher lumbar BMD Z-score in patients with a greater cumulative lifetime exposure to ICS (median >3 g) and a reduction in the number of patients at risk of fracture. We also found that the majority of our asthmatic patients (62.5%) who had higher cumulative ICS dose (more than 10 000 μg-years of cumulative budesonide-years) have normal BMD, although this was not statistically significant. We postulate that a higher dose of ICS given to asthmatic patients could have resulted in better asthma control which will then lead to an increase in physical activities and improved BMD.
In a large retrospective cohort study which included more than 100 000 patients in each arm, van Staa et al
] analyzed fracture risk among ICS users, inhaled bronchodilator users, and control subjects. The relative rates of non-vertebral, hip, and femur fractures among ICS users were higher than the control group, but not significantly different compared with the bronchodilator group. The authors concluded that ICS users had a higher risk of fracture, but this increased risk may be related to the underlying respiratory illness. They also found that the rate of fracture declined when treatment with ICS was discontinued.
Boulet et al
] studied 37 asthmatic subjects who had been using 800 μg/day or greater of beclomethasone or budesonide for more than 18 months, matched to a control group and found no significant difference in BMD between the two groups. In a separate study,[9
] 374 patients with mild asthma were randomized to receive inhaled budesonide, inhaled beclomethasone dipropionate, or non-corticosteroid treatment for two years, and the authors reported that there was no difference in the change of BMD between the three groups. It is worthwhile to note that the median daily doses of inhaled budesonide and beclomethasone were 389 μg and 499 μg, respectively, which one can argue were in the lower range of ICS dosages used to treat bronchial asthma and are unlikely to have any significant effect on BMD. To study the effect of high-dose ICS on BMD, Hughes et al
] recruited 59 patients with moderate-to-severe asthma and randomized them to receive inhaled fluticasone propionate 500 μg twice daily and inhaled budesonide 800 μg twice daily for one year. They, too, concluded that treatment with high doses of either inhaled fluticasone propionate or budesonide during the one year of treatment did not demonstrate any significant difference in BMD. The short one-year duration of study may not be sufficient to observe any effect that ICS may have on BMD.
Prolonged use of oral steroids leads to BMD deterioration and ultimately an increased risk of fracture,[20
] a fact not many clinicians will dispute. We attempted to include the usage of oral steroids as rescue therapy in our study to evaluate the effect of oral steroids on BMD in our study population. As expected, more patients who received one or more courses of rescue oral steroids in the preceding year had osteopenia or osteoporosis compared with those who did not, but the difference was not statistically significant. The small number of subjects in this sub-group analysis probably explained the lack of statistical significance. Furthermore, the one-year duration may be too short to demonstrate any effect of intermittent courses of oral steroids on BMD.
In conclusion, asthmatic patients on ICS had no added risk of osteoporosis or osteopenia. Risk factors for osteoporosis and osteopenia among asthmatic patients are older age and lower BMI but not the cumulative dose of ICS.
The major limitation of our study was the dependence on historical recall in the process of data gathering.