OP fracture risk by average daily dose of oral GC use in patients with rheumatoid arthritis, stratified by average daily dose and continuous duration of PPI use
| By recency of use | OP fractures (N=1411)* | IR per 1000 Pys | Age/sex-adjusted HR (95% CI) | Fully adjusted HR† (95% CI) |
| Non-use of GCs and PPIs | 325 | 10.5 | Reference | Reference |
| Current use of GCs and PPIs concomitantly‡ | 264 | 24.4 | 1.93 (1.65 to 2.27) | 1.60 (1.35 to 1.89) |
| ❶Low GC use (DD ≤7.5 mg PED/day) | ||||
| + Low-dose PPI use (DD <20 mg OEDs/day) | 142 | 23.2 | 1.75 (1.44 to 2.13) | 1.42 (1.16 to 1.74) |
| + Medium-dose PPI use (DD 20–35 mg OEDs/day) | 39 | 24.9 | 1.93 (1.39 to 2.69) | 1.54 (1.10 to 2.16) |
| + High-dose PPI use (DD >35 mg OEDs/day) | 8 | 34.2 | 2.72 (1.35 to 5.47) | 2.10 (1.04 to 4.24) |
| + Short-term continuous PPI use (≤1 year) | 89 | 25.7 | 2.00 (1.59 to 2.52) | 1.60 (1.26 to 2.04) |
| + Long-term continuous PPI use (>1 year) | 71 | 20.3 | 1.49 (1.15 to 1.93) | 1.18 (0.91 to 1.53) |
| + No continuous duration of PPI§ | 29 | 30.4 | 2.36 (1.62 to 3.45) | 2.00 (1.36 to 2.93)¶ |
| ❷Medium GC use (DD 7.6–14.9 mg PED/day) | ||||
| + Low-dose PPI use (DD <20 mg OEDs/day) | 43 | 25.0 | 2.22 (1.62 to 3.04) | 1.76 (1.27 to 2.43) |
| + Medium-dose PPI use (DD 20–35 mg OEDs/day) | 19 | 27.7 | 2.41 (1.52 to 3.82) | 1.92 (1.20 to 3.05) |
| + High-dose PPI use (DD >35 mg OEDs/day) | <5 | 17.2 | 1.46 (0.36 to 5.86) | 1.26 (0.31 to 5.07) |
| + Short-term continuous PPI use (≤1 year) | 36 | 30.2 | 2.70 (1.92 to 3.80) | 2.20 (1.55 to 3.11) |
| + Long-term continuous PPI use (>1 year) | 23 | 20.9 | 1.78 (1.17 to 2.72) | 1.37 (0.89 to 2.10) |
| + No continuous duration of PPI§ | 5 | 22.3 | 2.00 (0.83 to 4.84) | 1.67 (0.69 to 4.03) |
| ❸High GC use (DD ≥15.0 mg PED/day) | ||||
| + Low-dose PPI use (DD <20 mg OEDs/day) | 5 | 21.1 | 1.92 (0.79 to 4.64) | 1.58 (0.65 to 3.81) |
| + Medium-dose PPI use (DD 20–35 mg OEDs/day) | <5 | 38.8 | 3.77 (1.41 to 10.09) | 3.05 (1.13 to 8.18) |
| + High-dose PPI use (DD >35 mg OEDs/day) | <5 | 41.1 | 3.83 (0.95 to 15.37) | 3.30 (0.82 to 13.26) |
| + Short-term continuous PPI use (≤1 year) | 9 | 34.1 | 3.21 (1.66 to 6.21) | 2.72 (1.40 to 5.27) |
| + Long-term continuous PPI use (>1 year) | <5 | 11.3 | 0.99 (0.14 to 7.08) | 0.72 (0.10 to 5.15) |
| + No continuous duration of PPI§ | <5 | 27.1 | 2.65 (0.37 to 18.90) | 2.38 (0.33 to 16.97) |
Statistically significantly increased HRs are shown in bold.
*1411 OP fracture events among all included patients with RA. The number of fractures in exposure groups do not sum to this total due to not reporting the current only use and recent and past use of GCs and PPIs.
†Adjusted at baseline for sex, body mass index, smoking status and alcohol use; during follow-up for age, a history of anaemia, ankylosing spondylitis, chronic obstructive pulmonary disease, dementia, falls (in the past 7–12 months) and inflammatory bowel disease; use in the past 6 months of antidepressants, paracetamol, non-selective non-steroidal anti-inflammatory drugs, cyclo-oxygenase-2 selective inhibitors, tramadol, opioids and conventional synthetic disease-modifying antirheumatic drugs; and current only use and recent and past use of oral GCs and PPIs.
‡Concomitant current use refers to the most recent prescription of both oral GCs and PPIs in the 6 months before the start of a period.
§This represents fracture events that happened during a current period of PPI use but not eligible for a continuous duration of use calculation (ie, up to 6 months after the last PPI prescription, but after 1-month threshold gap of our definition for the continuous duration of PPI use).
¶Statistically different from long-term continuous PPI use within the same category, Wald test p<0.05.
DD, average daily dose; GCs, glucocorticoids; IR, incidence rate; OED, omeprazole equivalent dose; OP, osteoporotic; PED, prednisolone equivalent dose; PPIs, proton pump inhibitors; Pys, person years.