Introduction
Methods
Case–control study
Data source
Study population
Exposure
Potential confounders
Statistical analyses
Pooled analysis
Results
Case–control study
Characteristics | Cases n = 376,858 n (%) | Controls n = 376,858 n (%) |
---|---|---|
Women | 259,080 (68.7) | 259,080 (68.7) |
Mean age (years, SD) | 64.2 (19.5) | 64.2 (19.5) |
Mean age at index date (years, SD) | ||
18–49 years | 84,396 (22.4) | 84,375 (22.4) |
50–59 years | 53,441 (14.2) | 53,431 (14.2) |
60–69 years | 64,078 (17.0) | 64,109 (17.0) |
70–79 years | 77,058 (20.4) | 77,127 (20.4) |
80 + years | 97,885 (26.0) | 97,816 (26.0) |
History of comorbidities | ||
Myasthenia gravis | 130 (0.0) | 106 (0.0) |
Chronic obstructive pulmonary disease | 22,158 (5.9) | 16,844 (4.5) |
Previous fractures* | 99,268 (26.3) | 31,378 (8.3) |
Rheumatoid arthritis | 7,191 (1.9) | 5,303 (1.4) |
Inflammatory bowel disease | 7,722 (2.0) | 6,054 (1.6) |
Secondary osteoporosis | 18,490 (4.9) | 14,430 (3.8) |
Drug use within 6 months prior to index date | ||
Oral glucocorticoids | 19,476 (5.2) | 13,734 (3.6) |
Bisphosphonates | 10,427 (2.7) | 6,338 (1.7) |
Vitamin D | 419 (0.1) | 366 (0.1) |
Calcium | 5,139 (1.4) | 3,502 (0.9) |
Raloxifene | 450 (0.1) | 279 (0.1) |
Strontium ranelate | 157 (0.0) | 75 (0.0) |
Denosumab | 21 (0.0) | 7 (0.0) |
Parathyroid hormone | 112 (0.0) | 51 (0.0) |
Hormone replacement therapy | 22,532 (6.0) | 30,696 (8.1) |
Inhaled corticosteroids | 12,311 (3.3) | 10,832 (2.9) |
Inhaled bronchodilators | 25,220 (6.7) | 21,346 (5.7) |
Antipsychotics | 18,862 (5.0) | 11,698 (3.1) |
Antidepressants | 52,500 (13.9) | 31,158 (8.3) |
Hypnotics/anxiolytics | 41,553 (11.0) | 31,143 (8.3) |
Anticonvulsants | 11,995 (3.2) | 5,970 (1.6) |
Anti-Parkinson drugs | 4,307 (1.1) | 2,330 (0.6) |
Characteristics | Cases n = 130 n (%) | Controls n = 106 n (%) |
---|---|---|
Women | 97 (74.6) | 71 (67.0) |
Mean age (years, SD) | 70.2 (15.0) | 69.7 (17.7) |
Mean age at index date (years, SD) | ||
18–49 years | 17 (13.1) | 15 (14.2) |
50–59 years | 16 (12.3) | 13 (12.3) |
60–69 years | 25 (19.2) | 15 (14.2) |
70–79 years | 28 (21.5) | 25 (23.6) |
80 + years | 44 (33.7) | 38 (35.8) |
History of comorbidities | ||
Chronic obstructive pulmonary disease | 13 (10) | 14 (13.2) |
Previous fractures* | 38 (23.2) | 12 (11.3) |
Rheumatoid arthritis | a | a |
Inflammatory bowel disease | 7 (5.4) | a |
Secondary osteoporosis | 17 (13.1) | 6 (5.7) |
Drug use within 6 months prior to index date | ||
Oral glucocorticoids | 70 (53.8) | 54 (50.9) |
Bisphosphonates | 10 (7.7) | 10 (9.4) |
Vitamin D | a | a |
Calcium | 8 (6.2) | a |
Raloxifene | a | a |
Strontium ranelate | a | a |
Denosumab | a | a |
Parathyroid hormone | a | a |
Hormone replacement therapy | 13 (10.0) | 13 (12.3) |
Inhaled corticosteroids | 6 (4.6) | a |
Inhaled bronchodilators | 9 (6.9) | 6 (5.7) |
Antipsychotics | 6 (4.6) | a |
Antidepressants | 35 (26.9) | 14 (13.2) |
Hypnotics/anxiolytics | 15 (11.5) | 11 (10.4) |
Anticonvulsants | 7 (5.4) | 6 (5.7) |
Anti-Parkinson drugs | a | a |
Exposure | Number of cases | Number of controls | Crude OR (95% CI)a | Adjusted OR (95% CI)b | Number of cases | Number of controls | Crude OR (95% CI) a | Adjusted OR (95% CI) b |
---|---|---|---|---|---|---|---|---|
Myasthenia gravis | No myasthenia gravis | |||||||
No oral GC use | 60 | 52 | Reference | Reference | 313,936 | 322,430 | Reference | Reference |
Oral GC use | ||||||||
By recency of GC exposure | ||||||||
Distant past | 33 | 29 | 1.19 (0.72–1.97) | 1.02 (0.61–1.69) | 37,448 | 35,378 | 1.10 (1.08–1.12)* | 1.04 (1.02–1.06)* |
Past GC use | 8 | c | 2.03 (0.61–6.75) | 1.92 (0.56–6.54) | 5897 | 5231 | 1.17 (1.12–1.21)* | 1.07 (1.03–1.12)* |
Recent GC | c | c | 1.46 (0.33–6.56) | 1.39 (0.31–6.23) | 4721 | 3942 | 1.24 (1.19–1.30)* | 1.13 (1.09–1.19)* |
Current GC | 25 | 18 | 1.43 (0.78–2.62) | 1.26 (0.68–2.33) | 14,726 | 9771 | 1.56 (1.52–1.61)* | 1.37 (1.34–1.41)* |
By cumulative exposure (oral prednisolone equivalents) | ||||||||
< 1.0 g | c | c | Not determinedd | Not determinedd | 3104 | 2578 | 1.24 (1.18–1.31)* | 1.16 (1.10–1.23)* |
1.0–6.9 g | c | 8 | 0.65 (0.21–1.99) | 0.54 (0.18–1.67) | 6096 | 3987 | 1.59 (1.53–1.65)* | 1.39 (1.34–1.45)* |
≥ 7.0 g | 20 | 9 | 2.25 (1.03–4.95) * | 2.00 (0.90–4.44) | 5526 | 3206 | 1.80 (1.72–1.88)* | 1.53 (1.46–1.60)* |
By average daily dose (oral prednisolone equivalents) | ||||||||
< 7.5 mg | 6 | c | 1.24 (0.38–4.07) | 1.30 (0.39–4.33) | 8179 | 5912 | 1.44 (1.39–1.49)* | 1.28 (1.23–1.32)* |
7.5–14.9 mg | 11 | 8 | 1.40 (0.56–3.47) | 1.12 (0.45–2.83) | 4051 | 2605 | 1.61 (1.53–1.70)* | 1.39 (1.32–1.47)* |
≥ 15 mg | 8 | c | 1.65 (0.54–5.04) | 1.44 (0.46–4.47) | 2496 | 1254 | 2.06 (1.93–2.21)* | 1.77 (1.65–1.90)* |
Exposure | Number of cases | Number of controls | Crude OR (95% CI)a | Adjusted OR (95% CI)b | Number of cases | Number of controls | Crude OR (95% CI)a | Adjusted OR (95% CI)b |
---|---|---|---|---|---|---|---|---|
Myasthenia gravis | No myasthenia gravis | |||||||
No oral GC use | 125 | 121 | Reference | Reference | 876,322 | 897,151 | Reference | Reference |
Oral GC use by recency of GC exposure | ||||||||
Distant past | 54 | 46 | 1.23 (0.83–1.82) | 1.06 (0.71–1.58) | 87,137 | 78,088 | 1.16 (1.15–1.17)* | 1.10 (1.09–1.11)* |
Past GC use | 14 | c | 2.84 (1.02–7.89) | 2.73 (0.97–7.70) | 14,216 | 12,074 | 1.22 (1.19–1.25)* | 1.13 (1.10–1.16)* |
Recent GC | 13 | 10 | 1.37 (0.60–3.13) | 1.25 (0.54–2.89) | 10,551 | 8815 | 1.24 (1.20–1.28)* | 1.13 (1.10–1.16)* |
Current GC | 43 | 36 | 1.23 (0.79–1.92) | 1.08 (0.69–1.70) | 26,927 | 19,066 | 1.47 (1.44–1.49)* | 1.28 (1.26–1.31)* |
By cumulative exposure (oral prednisolone equivalents) | ||||||||
< 1.0 g | c | c | Not determinedd | Not determinedd | 7054 | 6012 | 1.21 (1.17–1.25)* | 1.13 (1.09–1.17)* |
1.0–6.9 g | 8 | 13 | 0.63 (0.26–1.53) | 0.59 (0.24–1.44) | 10,737 | 7519 | 1.48 (1.44–1.53)* | 1.29 (1.25–1.33)* |
≥ 7.0 g | 35 | 19 | 1.89 (1.08–3.30)* | 1.65 (0.93–2.91) | 9136 | 5535 | 1.73 (1.67–1.79)* | 1.44 (1.39–1.49)* |
By average daily dose (oral prednisolone equivalents) | ||||||||
< 7.5 mg | 13 | 13 | 1.04 (0.48–2.23) | 0.95 (0.43–2.08) | 15,728 | 12,016 | 1.36 (1.33–1.39)* | 1.21 (1.18–1.24)* |
7.5–14.9 mg | 19 | 14 | 1.40 (0.70–2.78) | 1.20 (0.59–2.42) | 6916 | 4641 | 1.55 (1.49–1.61)* | 1.33 (1.28–1.38)* |
≥ 15 mg | 11 | 9 | 1.25 (0.52–3.02) | 1.09 (0.45–2.66) | 4283 | 2409 | 1.84 (1.75–1.94)* | 1.57 (1.49–1.66)* |
Pooled analysis
Pooled HR (95% CI) | Heterogeneity I2 (%) | p value | Pooled HR (95% CI) | Heterogeneity I2 (%) | p value | |
---|---|---|---|---|---|---|
Major osteoporotic fracture | Any fracture | |||||
Current oral GC use | ||||||
By cumulative exposure (oral prednisolone equivalents) | ||||||
< 2.5 g | 0.58 (0.25–1.32) | 0 | 0.57 | 0.41 (0.07–2.30) | 67 | 0.08 |
2.5–5.0 g | 0.66 (0.28–1.55) | 0 | 0.40 | 0.69 (0.20–2.41) | 56 | 0.13 |
≥ 5.0 g | 1.60 (0.85–3.03) | 0 | 0.33 | 1.23 (0.57–2.63) | 51 | 0.15 |
By average daily dose (oral prednisolone equivalents) | ||||||
< 7.5 mg | 0.90 (0.42–1.94) | 0 | 0.44 | 0.97 (0.58–1.64) | 0 | 0.94 |
7.5–14.9 mg | 0.87 (0.42–1.82) | 0 | 0.39 | 1.10 (0.66–1.85) | 0 | 0.73 |
≥ 15 mg | 1.27 (0.63–2.57) | 0 | 0.79 | 1.00 (0.56–1.76) | 0 | 0.79 |