PPI or H2RA Use and the Risk of Fracture in Subgroup Meta-analyses Using a Random-Effects Model
| Factor | No. of Studies | Summary OR/RR (95% CI) | Heterogeneity I2, % |
|---|---|---|---|
| CI=confidence interval; H2RA = histamine 2 receptor antagonist; na = not available; NOS = Newcastle-Ottawa Scale; OR = odds ratio; PPI = proton pump inhibitor; RR=relative risk. | |||
| a Of the following variables: age, sex, body mass index, alcohol, smoking, medications that might have affected the risk of osteoporosis or fracture, physical activity or exercise, prior fracture or low-trauma fracture, calcium supplement or antiosteoporotic medications, hormone replacement therapy, history of stomach surgery or digestive system disorders, osteoporosis, family history of osteoporotic fracture. | |||
| Type of study | |||
| PPIs | 10 | 1.29 (1.18–1.41) | 69.8 |
| Case-control | 4 | 1.40 (1.13–1.75) | 73.7 |
| Nested case-control | 3 | 1.23 (1.03–1.47) | 85.8 |
| Cohort | 3 | 1.29 (1.13–1.47) | 38.7 |
| H2RAs | 7 | 1.10 (0.99–1.23) | 86.3 |
| Case-control | 3 | 1.11 (0.81–1.51) | 85.6 |
| Nested case-control | 2 | 1.20 (1.13–1.28) | 0 |
| Cohort | 2 | 1.08 (1.02–1.13) | 0 |
| Methodologic quality (NOS score) | |||
| PPIs | 10 | 1.29 (1.18–1.41) | 69.8 |
| High (>7 points) | 5 | 1.32 (1.18–1.47) | 63.7 |
| Low (≤7 points) | 5 | 1.25 (1.06–1.48) | 78.7 |
| H2RAs | 7 | 1.10 (0.99–1.23) | 86.3 |
| High (>7 points) | 3 | 1.13 (1.05–1.21) | 40.3 |
| Low (≤7 points) | 4 | 1.09 (0.87–1.38) | 90.6 |
| No. of adjustment variablesa | |||
| PPIs | 10 | 1.29 (1.18–1.41) | 69.8 |
| ≥5 | 6 | 1.36 (1.24–1.49) | 63.0 |
| <5 | 4 | 1.16 (0.98–1.38) | 66.5 |
| H2RAs | 7 | 1.10 (0.99–1.23) | 86.3 |
| ≥5 | 4 | 1.14 (1.06–1.22) | 57.7 |
| <5 | 3 | 1.11 (0.81–1.51) | 85.6 |
| Outcome | |||
| PPIs | |||
| Hip fracture | 9 | 1.31 (1.11–1.54) | 88.4 |
| Vertebral fracture | 3 | 1.56 (1.31–1.85) | 6.3 |
| Other fracture | 3 | 1.15 (0.94–1.42) | 78.2 |
| H2RAs | |||
| Hip fracture | 7 | 1.11 (0.95–1.29) | 81.2 |
| Other fracture | 3 | 1.01 (0.93–1.11) | 0 |
| Long-term use | |||
| PPIs | |||
| Any fracture | 10 | 1.30 (1.15–1.48) | 87.4 |
| Hip fracture | 9 | 1.34 (1.09–1.66) | 87.4 |
| H2RAs | |||
| Any fracture | 6 | 1.11 (0.95–1.30) | 88.9 |
| Hip fracture | 6 | 1.14 (0.90–1.43) | 87.2 |
| Dose (hip fracture) | |||
| PPIs | |||
| High dose | 4 | 1.53 (1.18–1.97) | 81.6 |
| Usual dose | 4 | 1.42 (1.31–1.53) | 32.6 |
| H2RAs | |||
| High dose | 4 | 1.14 (0.84–1.54) | 92.3 |
| Usual dose | 4 | 1.05 (0.89–1.26) | 82.2 |
| Sex | |||
| PPIs | |||
| Male (hip fracture) | 4 | 1.24 (0.93–1.65) | 89.9 |
| Female (hip or vertebral fracture) | 5 | 1.21 (0.98–1.50) | 88.8 |
| H2RAs | |||
| Male (hip fracture) | 2 | 1.60 (0.92–2.77) | 0 |