Table 2.
Signal detection between any proton pump inhibitor (PPI) and reported fracture adverse events as classified by MedDRA’s 8 High Level Terms (HLT) and corresponding 61 Preferred Terms (PT), by overall and age groups.
| Fracture Site | Proportional Rate Ratio (PRR) by Age Groups (years) | |||||||
|---|---|---|---|---|---|---|---|---|
| Overall | ≤49 | 50–69 | ≥70 | |||||
| N | PRR(χ2) | N | PRR(χ2) | N | PRR(χ2) | N | PRR(χ2) | |
| Skull and face fractures | 113 | 1.7(29.5) | 22 | 1.2(0.6) | 35 | 1.9(12.1) | 39 | 2.3(25.5) |
| Skull fractured base | 8 | 2.8(7.9) | 2 | 2.1(1.0) | 3 | 5.1(7.1) | 3 | 3.7(4.6) |
| Skull fracture | 24 | 1.2(0.7) | 8 | 1.2(0.2) | 5 | 0.9(<0.1) | 7 | 1.5(1.1) |
| Facial bones fracture | 81 | 1.8(25.7) | 12 | 1.0(<0.1) | 27 | 2.0(12.2) | 29 | 2.5(22.5) |
| Fractured skull depressed | 0 | — | 0 | — | 0 | — | 0 | — |
| Thoracic cage fractures non-spinal (excl pathological) | 437 | 2.5(323.5) | 52 | 1.6(11.8) | 165 | 2.6(139.0) | 137 | 2.9(143.0) |
| Sternal fracture | 22 | 1.9(9.5) | 6 | 2.8(5.7) | 11 | 3.1(12.7) | 3 | 1.0(<0.1) |
| Rib fracture | 423 | 2.5(325.4) | 47 | 1.6(8.9) | 160 | 2.6(136.9) | 135 | 3.0(151.3) |
| Flail chest | 2 | 2.5(1.5) | 0 | — | 1 | 13.5(5.8) | 1 | 2.3(0.6) |
| Spinal fractures (excl pathological) | 517 | 2.2(290.7) | 52 | 1.6 (9.3) | 181 | 2.6(155.4) | 188 | 2.4(136.5) |
| Spinal fracture | 323 | 2.3(209.9) | 30 | 1.6(5.4) | 108 | 2.9(112.0) | 117 | 2.5(91.4) |
| Cervical vertebral fracture | 50 | 1.8(16.3) | 7 | 1.3(0.5) | 14 | 1.9(5.3) | 17 | 2.5(12.6) |
| Thoracic vertebral fracture | 58 | 2.6(47.7) | 4 | 1.1(0.1) | 26 | 3.2(31.7) | 21 | 2.9(21.0) |
| Lumbar vertebral fracture | 68 | 1.9(27.3) | 7 | 1.7(1.9) | 29 | 2.6(23.5) | 24 | 1.9(8.7) |
| Fractured sacrum | 43 | 3.6(64.0) | 5 | 3.1(5.7) | 15 | 3.4(20.1) | 18 | 5.0(41.6) |
| Fractured coccyx | 13 | 1.2(0.6) | 3 | 1.2(0.1) | 4 | 1.1(<0.1) | 3 | 1.1(<0.1) |
| Pelvic fractures | 200 | 2.1(98.4) | 11 | 1.0(<0.1) | 54 | 2.2(30.3) | 90 | 2.3(55.1) |
| Pelvic fracture | 160 | 1.9(62.6) | 10 | 1.2(0.2) | 40 | 2.0(18.0) | 70 | 1.9(29.0) |
| Ilium fracture | 4 | 1.4(0.3) | 0 | — | 2 | 1.8(0.6) | 1 | 1.4(0.1) |
| Pubis fracture | 26 | 3.8(41.5) | 0 | — | 11 | 4.4(21.6) | 13 | 4.2(24.0) |
| Acetabulum fracture | 14 | 3.6(21.1) | 1 | 0.9(0.01) | 4 | 2.8(3.9) | 7 | 7.9(26.6) |
| Fractured ischium | 2 | 1.0(<0.1) | 0 | — | 1 | 1.2(<0.1) | 1 | 1.5(0.2) |
| Upper limb fractures | 768 | 1.8(249.3) | 87 | 1.2(3.4) | 287 | 1.9(123.5) | 270 | 2.4(179.5) |
| Upper Limb fracture | 282 | 1.7(69.6) | 22 | 0.9(0.3) | 106 | 1.8(34.2) | 108 | 2.5(81.9) |
| Clavicle fracture | 57 | 1.7(15.1) | 11 | 1.3(0.9) | 20 | 1.9(8.2) | 15 | 2.1(7.8) |
| Scapula fracture | 14 | 2.7 (12.5) | 3 | 2.5(2.3) | 8 | 5.4(20.5) | 2 | 1.6(0.4) |
| Humerus fracture | 114 | 2.2(61.4) | 10 | 1.3(0.6) | 44 | 2.5(32.7) | 41 | 2.3(25.7) |
| Forearm fracture | 10 | 1.8(3.3) | 2 | 2.1(1.0) | 6 | 4.3(11.4) | 2 | 1.1(<0.1) |
| Radius fracture | 65 | 2.6(51.6) | 10 | 1.9(3.9) | 23 | 2.4(15.8) | 26 | 3.6(38.3) |
| Ulna fracture | 30 | 3.0(32.3) | 5 | 2.3(3.2) | 17 | 5.3(43.0) | 4 | 1.3(0.3) |
| Wrist fracture | 205 | 1.9(78.7) | 21 | 1.5(3.2) | 75 | 1.9(28.4) | 82 | 2.6(66.4) |
| Hand fracture | 100 | 1.9(38.9) | 24 | 1.8(7.3) | 34 | 1.9(11.7) | 20 | 2.3(12.9) |
| Scapulothoracic dissociation | 0 | — | 0 | — | 0 | — | 0 | — |
| Lower limb fractures | 1714 | 1.5(270.0) | 161 | 1.1(1.6) | 662 | 1.7(177.0) | 609 | 1.9(237.7) |
| Lower limb fracture | 202 | 1.4(24.0) | 25 | 0.9(0.1) | 94 | 1.8(30.7) | 41 | 1.6(7.8) |
| Hip fracture | 497 | 1.7(136.7) | 23 | 1.4(2.4) | 121 | 1.6(24.4) | 264 | 2.3(159.9) |
| Femoral neck fracture | 81 | 1.5(12.5) | 4 | 1.0(0.0) | 25 | 2.1(13.1) | 43 | 1.5(5.8) |
| Femur fracture | 454 | 1.3(24.8) | 32 | 1.4(2.9) | 203 | 1.6(40.2) | 177 | 1.7(44.1) |
| Patella fracture | 35 | 1.7(8.2) | 3 | 0.9(0.1) | 17 | 2.1(8.3) | 10 | 1.9(3.4) |
| Tibia fracture | 92 | 1.9(37.8) | 9 | 0.8(0.6) | 42 | 2.1(21.8) | 29 | 3.6(42.3) |
| Fibula fracture | 71 | 2.2(39.7) | 11 | 1.4(0.9) | 34 | 2.4(23.1) | 14 | 2.5(10.8) |
| Ankle fracture | 223 | 1.5(31.1) | 22 | 0.6(4.7) | 103 | 1.6(23.3) | 42 | 1.8(12.4) |
| Foot fracture | 291 | 1.8(97.1) | 56 | 1.5(8.4) | 149 | 2.2(79.3) | 39 | 1.9(15.8) |
| Fractures NEC (excl pathological) | 638 | 1.9(277.9) | 80 | 1.7(18.8) | 269 | 2.6(225.7) | 185 | 2.3(115.8) |
| Periprosthetic fracture | 4 | 4.9(9.1) | 0 | — | 2 | 3.9(3.3) | 2 | 13.5(11.6) |
| Fracture displacement | 18 | 4.2(33.4) | 1 | 2.7(0.9) | 8 | 3.6(11.9) | 8 | 5.4(20.5) |
| Compression fracture | 169 | 3.7(256.9) | 17 | 4.2(31.4) | 73 | 5.4(185.3) | 53 | 2.9(54.3) |
| Bone fragmentation | 28 | 3.6(41.5) | 2 | 1.7(0.5) | 18 | 5.5(47.3) | 4 | 1.9(1.4) |
| Avulsion fracture | 5 | 2.7(4.5) | 1 | 1.4(0.1) | 2 | 3.9(3.3) | 2 | 4.5(4.1) |
| Jaw fracture | 77 | 2.5(61.0) | 12 | 1.7(3.2) | 37 | 2.9(38.5) | 17 | 3.1(20.2) |
| Bone fissure | 6 | 1.3(0.3) | 1 | 2.3(0.6) | 1 | 0.4(0.7) | 3 | 2.5(2.3) |
| Complicated fracture | 3 | 3.5(0.1) | 0 | — | 2 | 13.5(11.6) | 1 | 3.4(1.3) |
| Epiphyseal fracture | 1 | 3.4(1.3) | 1 | 3.4(1.3) | 0 | — | 0 | — |
| Fracture | 168 | 1.3(13.9) | 12 | 1.0(0.0) | 64 | 2.3(38.1) | 51 | 1.6(11.4) |
| Impacted fracture | 1 | 2.7(0.9) | 0 | — | 0 | — | 0 | — |
| Multiple fractures | 59 | 1.7(15.0) | 8 | 1.0(0.0) | 23 | 2.2(13.0) | 18 | 2.5(14.1) |
| Open fracture | 13 | 1.9(5.1) | 3 | 1.6(0.5) | 3 | 1.3(0.2) | 3 | 2.5(2.3) |
| Stress fracture | 116 | 1.9(40.8) | 17 | 3.1(19.7) | 55 | 2.0(24.0) | 30 | 2.5(23.7) |
| Torus fracture | 1 | 3.4(1.3) | 1 | 4.5(2.0) | 0 | — | 0 | — |
| Traumatic fracture | 11 | 1.5(1.9) | 0 | — | 4 | 1.5(0.6) | 4 | 2.2(2.2) |
| Greenstick fracture | 0 | — | 0 | — | 0 | — | 0 | — |
| Pathological fractures and complications | 277 | 2.6(223.3) | 32 | 1.8(10.3) | 119 | 2.7(103.8) | 94 | 3.6(137.4) |
| Pathological fracture | 188 | 3.1(218.6) | 20 | 2.5(14.9) | 78 | 3.2(93.5) | 72 | 4.3(137.6) |
| Pseudarthrosis | 8 | 2.3(5.3) | 3 | 4.1(5.3) | 4 | 3.2(4.8) | 1 | 1.1(<0.1) |
| Osteoporotic fracture | 31 | 2.3(19.7) | 5 | 1.2(0.1) | 7 | 2.3(4.4) | 12 | 3.7(18.4) |
| Fracture nonunion | 39 | 2.2(21.8) | 4 | 1.6(0.9) | 24 | 2.3(15.8) | 6 | 2.2(3.3) |
| Fracture malunion | 2 | 0.8(0.1) | 0 | — | 1 | 0.8(<0.1) | 0 | — |
| Fracture delayed union | 20 | 1.7(5.1) | 1 | 0.9(0.01) | 11 | 1.7(3.1) | 7 | 2.3(4.2) |
| Synostosis | 1 | 0.5(0.6) | 0 | — | 0 | — | 1 | — |
Around 82% of reports have age information. Bold indicates statistically significant signals.