Table 1

Description of studies with bone density as an outcome

Primary author	Sasagawa22	Sosa20	Langhammer21	Israel18	Tattersfield19	Kemp17
Year	2011	2006	2004	2001	2001	2004
Study design	Case-control	Cross-sectional	Cross-sectional	Cohort	RCT	Double blind RCT
Length of study/follow-up	Follow-up was 6 months	ICS >1 year before study entry	Variable	3 years	2 years	104 weeks
Population	Japan	Canary Islands, Spain	Norway	Premenopausal women	19 centres across France, New Zealand, Spain and the UK	Not reported
Sample size	198 ICS users; 93 controls	105 cases; 133 controls	8624	109	239	160
Age range	16 years +	18 years +	20 years +	18–45 years	20–60 years	18–50 years for men, 18–40 years for women
Asthma diagnosis definition	Physician diagnosed, no details	Physician diagnosed, no details	Self-reported	Physician diagnosed, no details	Relatively mild asthma and prebronchodilator FEV₁ of 65% predicted or above	Mean FEV₁ 82%–85% of predicted
ICS type (drug/name)	Fluticasone propionate, budesonide, beclomethasone	Not specified	Beclometasone dipropionate, budesonide, fluticasone propionate	Triamcinolone acetonide	Budesonide, beclomethasone	Fluticasone propionate
Control/comparison group	Volunteers or other diseases—not using ICS	Friends and neighbours of the patients, not on ICS or have asthma	Never used corticosteroids and not used β2-agonists in the last month; asthma or randomly selected general population	Premenopausal asthmatic women taking no ICS	Non-ICS for example, LABA, sodium cromoglycate, nedocromil sodium, ipratropium bromide or theophylline	Placebo
Bone tested	Calcaneus	Calcaneus and lumbar and femur	Wrist	Lumbar and femur and trochanter	Femur and lumbar	Lumbar and femur
Density measure	Ultrasound	Ultrasound and DEXA	Single energy X-ray absorptiometry	DEXA	DEXA	DEXA
Secondary outcome of study	N/A	N/A	N/A	N/A	Lung function Relation between change in bone density and inhaled steroid dose Change in biochemical markers of bone metabolism	AEs
Statistical analysis	χ²	Logistic regression	Linear regression	Proc Mixed programme of the SAS software package	ANOVA	ANCOVA
Adjusted covariates	N/A	Age	Age, square age, height, BMI, number of pack years cigarettes, physical activity, work physical load, family history of osteoporosis, years since menopause, HRT	Age, use of oral contraceptives, use of oral glucocorticoids, use of topical nasal glucocorticoid preparations	Baseline BMD, age (group), sex and country. Change was related to dose of ICS, mean lung function and change in markers of bone metabolism	Baseline value, investigator, sex and age effect
Crude results	First %OSI controls=100.7; cases=102.8 (p=0.12) second %OSI controls=100.5; cases=102.1 (p=0.12)		N/A	In all women, yearly change (g/cmˆ2/puff)—total hip: −0.00044±0.00017; trochanter: −0.00044±0.00016; femoral neck: −0.00005±0.00028; spine: −0.00008±0.00019 In women who received no oral or parenteral glucocorticoid therapy—total hip: −0.00041±0.00019; trochanter: −0.00048±0.00019; femoral neck: −0.00015±0.00030; spine: −0.00001±0.00020	Mean % change in BMD from baseline in subjects completing the study at month 24 (budesonide): lumbar=0.1%, neck of femur=−0.9%, total body=0.6% Mean % change in BMD from baseline in subjects completing the study at month 24 (beclomethasone): lumbar=−0.4%, neck of femur=−0.9%, total body=0.4%	N/A
Adjusted results	N/A	Age-adjusted OR=2.79 (95% CI 1.19 to 6.54)	Adjusted mean difference in distal BMD (x10ˆ−3): control versus ICS only Women: −11.5 (p<0.01). 95% CI −17.1 to –6.0 Men: −12.4 (p<0.01). 95% CI −18.2 to –6.5	In all women, yearly change (g/cmˆ2/puff)—total hip: −0.00048±0.00018; trochanter: −0.00042±0.00017; femoral neck: −0.00017±0.00028; spine: −0.00012±0.00018. In women who received no oral or parenteral glucocorticoid therapy—total hip: −0.00041±0.00020; trochanter: −0.00047±0.00019; femoral neck: −0.00015±0.00031; spine: −0.00015±0.00019	Estimated difference between treatments in % change in BMD over 2 years after adjusting (budesonide vs reference): lumbar=−0.35%, neck of femur=−0.70%, total body=−0.42% Estimated difference between treatments in % change in BMD over 2 years after adjusting (beclomethasone vs reference): lumbar=−0.83%, neck of femur=−0.52%, total body=−0.55%	Change in total BMD in placebo=0.008 (0.004) (mean (SE)). Change in FP 88 mcg=0.008 (0.003). Change in FP 440 mcg=0.002 (0.003)

AE, adverse events; ANOVA, analysis of variance; BMD, bone mineral density; BMI, body mass index; DEXA, dual energy X-ray absorptiometry; FEV₁, forced expiratory volume in 1 s; FP, fluticasone proprionate; HRT, hormone replace test; ICS, inhaled corticosteroid; LABA, long-acting beta agonist; %OSI, osteo sono assessment index; RCT, randomised controlled trial; SAS, statistical analysis software.