Table 2.
Odds ratios and 95% confidence intervals for the risk of osteoporotic fracture associated with PPI use compared to exclusive H2RA use
| Osteoporotic fracture | OR (95% CI) | |||||
|---|---|---|---|---|---|---|
| Cases | Controls | |||||
| n | (%) | n | (%) | Crude | Adjusteda | |
| Any use | ||||||
| H2RA use | 35,929 | (61) | 192,458 | (65) | 1 (Reference) | 1 (Reference) |
| PPI use | 23,311 | (39) | 103,742 | (35) | 1.24 (1.22–1.27) | 1.11 (1.08–1.13) |
| Duration of use | ||||||
| H2RA use | 35,929 | (61) | 192,458 | (65) | 1 (Reference) | 1 (Reference) |
| < 30 days | 10,715 | (17) | 51,337 | (18) | 1.15 (1.13–1.18) | 1.08 (1.06–1.11) |
| 30–59 days | 4773 | (7) | 21,788 | (8) | 1.22 (1.18–1.26) | 1.09 (1.05–1.13) |
| 60–89 days | 2405 | (4) | 10,408 | (4) | 1.29 (1.23–1.35) | 1.11 (1.06–1.17) |
| 90–179 days | 2747 | (4) | 11,249 | (5) | 1.37 (1.31–1.44) | 1.13 (1.08–1.19) |
| 180–364 days | 1505 | (2) | 5417 | (3) | 1.57 (1.48–1.67) | 1.18 (1.11–1.26) |
| ≥ 365 days | 1166 | (1) | 3543 | (2) | 1.88 (1.75–2.01) | 1.42 (1.32–1.52) |
| P for trend | < 0.001 | < 0.001 | ||||
| Recent useb | ||||||
| No recent use | 53,019 | (90) | 274,084 | (93) | 1 (Reference) | 1 (Reference) |
| One quarter | 3812 | (6) | 14,123 | (5) | 1.41 (1.35–1.46) | 1.24 (1.19–1.29) |
| Two quarters | 1156 | (2) | 4119 | (1) | 1.47 (1.37–1.57) | 1.19 (1.11–1.27) |
| Three quarters | 564 | (1) | 1793 | (1) | 1.64 (1.49–1.81) | 1.32 (1.20–1.46) |
| All quarters (regular use) | 689 | (1) | 2081 | (1) | 1.73 (1.59–1.89) | 1.37 (1.26–1.50) |
| P for trend | < 0.001 | < 0.001 | ||||
PPI use was defined as having been prescribed PPI at least once during the follow-up period
Concomitant diseases were defined using the ICD-10 codes and included chronic obstructive pulmonary disease (J44, 45), testicular dysfunction (E29.1), hypothalamic dysfunction (E23.0), hyperthyroidism (E05), hyperparathyroidism (E21), Cushing’s syndrome (E24), hyperprolactinemia (E22.1), vitamin D deficiency (E55.9), idiopathic hypercalciuria (E83.5), diabetes (E11–14 and diabetic agents), anorexia nervosa (F50.0, 50.1), systemic lupus erythematous (M32), hypertension (I10–13, I15, and use of antihypertensive agents), intestinal absorption disorder (K90), inflammatory bowel disease (K50, 51), chronic kidney disease (N18), and secondary amenorrhea (N91.1)
Abbreviations: H2RA histamine-2 receptor antagonist, PPI proton pump inhibitor, Ref. reference
aAdjusted for age, sex, body mass index, alcohol drinking, smoking, physical activity, bisphosphonates, glucocorticoids, anticonvulsants, hormone replacement therapy, warfarin, heparin, antacids, selective serotonin reuptake inhibitors, benzodiazepines, tricyclic antidepressants, diabetes mellitus, chronic obstructive pulmonary disease, hypothyroidism, hypopituitarism, hyperparathyroidism, Cushing’s syndrome, hyperprolactinemia, vitamin D deficiency, idiopathic hypercalcemia, intestinal absorption disorder, chronic liver disease, rheumatoid arthritis, hyperthyroidism, chronic kidney disease, chronic obstructive pulmonary disease, anorexia nervosa, systemic lupus erythematosus, inflammatory bowel disease, secondary amenorrhea, and hypertensive disease
bThe number of quarters with PPI use during the year prior to fracture was identified. The use of PPI over all quarters was defined as ‘regular use’