OP fracture risk by concomitant use of oral GCs and PPIs in patients with rheumatoid arthritis, stratified by fracture type
| By recency of use | Hip (N=541) | Clinical vertebral (N=224) | Humerus (N=372) | Forearm (N=302) | Pelvis (N=116) | Rib (N=90) | ||||||
| IR per 1000 Pys | Fully adjusted HR* (95% CI) | IR per 1000 Pys | Fully adjusted HR† (95% CI) | IR per 1000 Pys | Fully adjusted HR‡ (95% CI) | IR per 1000 Pys | Fully adjusted HR§ (95% CI) | IR per 1000 Pys | Fully adjusted HR¶ (95% CI) | IR per 1000 ys | Fully adjusted HR** (95% CI) | |
| Non-use of GCs and PPIs | 3.8 | Reference | 1.0 | Reference | 2.9 | Reference | 2.5 | Reference | 0.6 | Reference | 0.6 | Reference |
| Current use†† | ||||||||||||
| GCs and PPIs concomitantly | 9.0 | 1.45 (1.11 to 1.91) | 5.4 | 2.84 (1.87 to 4.32) | 5.8 | 1.29 (0.93 to 1.78) | 2.9 | 0.87 (0.57 to 1.32) | 2.9 | 2.47 (1.41 to 4.34) | 1.7 | 4.03 (2.13 to 7.63) |
| GCs alone | 6.0 | 1.26 (0.95 to 1.66) | 1.8 | 1.31 (0.79 to 2.16)‡‡ | 3.3 | 0.99 (0.69 to 1.43) | 3.2 | 1.17 (0.81 to 1.70) | 0.9 | 1.07 (0.54 to 2.14)‡‡ | 1.2 | 2.28 (1.17 to 4.46) |
| PPIs alone | 5.9 | 1.10 (0.86 to 1.41) | 3.1 | 1.78 (1.20 to 2.65)‡‡ | 4.5 | 1.17 (0.88 to 1.55) | 3.3 | 0.98 (0.71 to 1.37) | 1.6 | 1.93 (1.11 to 3.34) | 0.8 | 1.24 (0.66 to 2.34)‡‡ |
| Recent GC use†† §§ | 5.9 | 1.25 (0.78 to 2.01) | 1.2 | 0.59 (0.22 to 1.63) | 1.5 | 0.42 (0.17 to 1.03) | 3.1 | 1.00 (0.52 to 1.91) | 1.2 | 0.97 (0.35 to 2.72) | 0.6 | 1.21 (0.29 to 5.14) |
| Recent PPI use†† §§ | 5.3 | 1.00 (0.60 to 1.65) | 2.8 | 1.73 (0.85 to 3.54) | 3.4 | 0.93 (0.50 to 1.72) | 3.7 | 1.09 (0.60 to 2.00) | 0.9 | 1.16 (0.35 to 3.87) | 1.5 | 2.17 (0.83 to 5.62) |
| Past GC use†† §§ | 5.5 | 1.08 (0.86 to 1.35) | 2.4 | 1.12 (0.78 to 1.59) | 3.7 | 0.98 (0.75 to 1.27) | 3.6 | 1.19 (0.90 to 1.58) | 0.8 | 0.64 (0.37 to 1.11) | 1.2 | 2.43 (1.39 to 4.22) |
| Past PPI use†† §§ | 5.4 | 0.98 (0.76 to 1.27) | 1.9 | 1.11 (0.71 to 1.74) | 2.7 | 0.72 (0.51 to 1.01) | 3.0 | 0.86 (0.61 to 1.21) | 0.9 | 1.17 (0.62 to 2.20) | 0.6 | 0.86 (0.43 to 1.75) |
Statistically significantly increased HRs are shown in bold.
*Adjusted at baseline for sex, BMI, smoking status and alcohol use; during follow-up for age, a history of anaemia, AS, COPD, dementia, falls (in the past 7–12 months) and IBD; and use in the past 6 months of antidepressants, hypnotics/anxiolytics, paracetamol, non-selective NSAIDs, COX-2 selective inhibitors, tramadol, opioids and csDMARDs.
†Adjusted at baseline for sex, BMI, smoking status and alcohol use; during follow-up for age, a history of COPD, falls (in the past 7–12 months) and IBD; and use in the past 6 months of antidepressants, anticonvulsants, paracetamol, non-selective NSAIDs, COX-2 selective inhibitors, tramadol, opioids and csDMARDs.
‡Adjusted at baseline for sex, BMI, smoking status and alcohol use; during follow-up for age, a history of anaemia, AS, COPD, dementia, falls (in the past 7–12 months) and IBD; and use in the past 6 months of antidepressants, paracetamol, non-selective NSAIDs, COX-2 selective inhibitors, tramadol, opioids and csDMARDs.
§Adjusted at baseline for sex, BMI, smoking status and alcohol use; during follow-up for age, a history of anaemia, type 2 diabetes mellitus, COPD, dementia, falls (in the past 7–12 months), gastro-oesophageal reflux disease and IBD; and use in the past 6 months of antidepressants, anticoagulants, anticonvulsants, antihypertensives, paracetamol, non-selective NSAIDs, COX-2 selective inhibitors, tramadol, opioids and csDMARDs.
¶Adjusted at baseline for sex, during follow-up for age and use in the past 6 months of antidepressants, paracetamol and opioids.
**Adjusted at baseline for sex and during follow-up for age.
††Current, recent and past use refer to the last prescription within 6 months, 7–12 months and >12 months before a period, respectively.
‡‡Statistically different from concomitant GC and PPI use within the same fracture type, Wald test p<0.05.
§§Regardless of the use of the other drug.
AS, ankylosing spondylitis; BMI, body mass index; COPD, chronic obstructive pulmonary disease; COX-2, cyclo-oxygenase-2; csDMARDs, conventional synthetic disease-modifying antirheumatic drugs; GCs, glucocorticoids; ; IBD, inflammatory bowel disease; IR, incidence rate; NSAIDs, non-steroidal anti-inflammatory drugs; OP, Osteoporotic; PPIs, proton pump inhibitors; Pys, person years.