7. Drug‐related adverse effects reported in randomised versus non‐randomised bisphosphonates trials.
| Study ID | Comparison | Adverse effect | Bisphosphonate 1 | Bisphosphonate 2 | RR (95% CI) |
| Roux 1995 | Tiludronate (155) vs. etidronate (79) | Gastrointestinal | 32 (20.8%) | 10 (12.7%) | 1.63 (0.85 to 3.14) |
| Abdominal pain | 10 (6.5%) | 2 (2.5%) | 2.55 (0.57 to 11.35) | ||
| Nausea, vomiting | 8 (5.2%) | 2 (2.5%) | 2.04 (0.44 to 9.37) | ||
| Fracture | 1 (1%) | 2 (3%) | 0.25 (0.02 to 2.77) | ||
| Siris 1996 | Alendronate (42) vs. etidronate (47) |
Gastrointestinal | 11 (26%) | 10 (21%) | 1.23 (0.58 to 2.60) |
| Abdominal distention | 0 (%) | 1 (2%) | 0.37 (0.02 to 8.90) | ||
| Abdominal pain | 3 (7%) | 4 (9%) | 0.84 (0.2 to 3.54) | ||
| Acid regurgitation | 1 (2%) | 1 (2%) | 1.12 (0.07 to 17.34) | ||
| Dyspepsia | 0 (0%) | 1 (2%) | 0.37 (0.02 to 8.90) | ||
| Melena | 1 (2%) | 0 (0%) | 3.35 (0.14 to 80.05) | ||
| Nausea | 2 (5%) | 3 (6%) | 0.75 (0.13 to 4.25) | ||
| Leg pain | 1 (2%) | 9 (19%) | 0.12 (0.02 to 0.94) | ||
| Laboratory adverse experiences | 9 (21%) | 6 (13%) | 1.68 (0.65 to 4.32) | ||
| Miller 1999 | Risedronate (62) vs. etidronate (61) |
Upper gastrointestinal | 12 (19%) | 12 (20%) | 0.98 (0.48 to 2.02) |
| Barreira 2009 | Olpadronate (14) vs. pamidronate (7) |
Digestive | 9 (64%) | 7 (100%) | 0.68 (0.44 to 1.03) |
| Merlotti 2007* | Zoledronate (47)* vs. pamidronate (60) |
Influenza‐like illness | 4 (9%) | 5 (8%) | 1.02 (0.29 to 3.59) |
| Myalgia | 3 (6%) | 4 (7%) | 0.96 (0.23 to 4.07) | ||
| Pyrexia | 3 (6%) | 4 (7%) | 0.96 (0.23 to 4.07) | ||
| Fatigue | 3 (6%) | 8 (13%) | 0.48 (0.13 to 1.71) | ||
| Headache | 4 (9%) | 5 (8%) | 1.02 (0.29 to 3.59) | ||
| Diarrhoea | 1 (2%) | 2 (3%) | 0.64 (0.06 to 6.83) | ||
| Bone pain | 3 (6%) | 6 (10%) | 0.64 (0.17 to 2.42) | ||
| Pain in arm or leg | 3 (6%) | 4 (7%) | 0.96 (0.23 to 4.07) | ||
| Hypocalcaemia | 3 (6%) | 1 (2%) | 3.83 (0.41 to 35.64) | ||
| Dermatitis | 1 (2%) | 0 (0%) | 0.42 (0.02 to 10.17) | ||
| Reid 2005 | Zoledronate (177) vs. risedronate (172) |
Study days 1 to 3 | |||
| Influenza‐like illness | 17 (9.6%) | 7 (4.1%) | 2.36 (1 to 5.55) | ||
| Myalgia | 13 (7.3%) | 6 (3.5%) | 2.11 (0.82 to 5.41) | ||
| Pyrexia | 13 (7.3%) | 1 (0.6%) | 12.63 (1.67 to 95.53) | ||
| Fatigue | 12 (6.8%) | 4 (2.3%) | 2.92 (0.96 to 8.86) | ||
| Headache | 12 (6.8%) | 7 (4.1%) | 1.67 (0.67 to 4.13) | ||
| Rigor | 12 (6.8%) | 1 (0.6%) | 11.66 (1.53 to 88.72) | ||
| Nausea | 11 (6.2%) | 3 (1.7%) | 3.56 (1.01 to 12.55) | ||
| Bone pain | 9 (5.1%) | 2 (1.2%) | 4.37 (0.96 to 19.95) | ||
| After study day 3 | |||||
| Pain in an arm or leg | 13 (7.3%) | 12 (7%) | 1.05 (0.49 to 2.24) | ||
| Arthralgia | 9 (5.1%) | 19 (11%) | 0.46 (0.21 to 0.99) | ||
| Dizziness | 9 (5.1%) | 5 (2.9%) | 1.75 (0.6 to 5.11) | ||
| Nasopharyngitis | 9 (5.1%) | 14 (8.1%) | 0.62 (0.28 to 1.41) | ||
| Diarrhoea | 8 (4.5%) | 9 (5.2%) | 0.86 (0.34 to 2.19) | ||
| Headache | 7 (4%) | 10 (5.8%) | 0.68 (0.26 to 1.75) | ||
| Back pain | 4 (2.3%) | 12 (7.0%) | 0.32 (0.11 to 0.98) | ||
| Symptomatic hypocalcaemia | 2 (1.1%) | 1 (0.6%) | 1.94 (0.18 to 21.24) | ||
| Reid 2011 (extension) | Zoledronate (152) vs. risedronate (115) |
Atrial fibrillation | 1 (0.7%) | 1 (0.9%) | 0.76 (0.05 to 12.20) |
| Atrial flutter | 0 (0%) | 2 (1.7%) | 0.15 (0.01 to 3.13) | ||
| Osteonecrosis jaw | 0 (0%) | 0 (0%) | ‐ | ||
| Walsh 2004 | Alendronate (36) vs. pamidronate (36) |
Gastrointestinal | 16 (44%) | 4 (11%) | 4 (1.48 to 10.80) |
| Fatigue | 0 (0%) | 23 (64%) | 0.02 (0.00 to 0.34) | ||
| General aches/pain | 4 (11%) | 16 (44%) | 0.25 (0.09 to 0.68) | ||
| Deteriorating kidney failure | 1 (3%) | 0 (0%) | 3.00 (0.12 to 71.28) | ||
*Zoledronate group data were extracted from Table 3 in Merlotti 2007. In this table, the authors presented data from 30 participants who took part in the first part of the study (which was included in our systematic review) plus 17 participants from the second part of the study (which was not included in our systematic review).