Table 1. The results of the literature review.
PTH - parathyroid hormone; PPI - proton pump inhibitors; HR - hazard ratio; OR - odds ratio; BP - bisphosphonate; H2RA - histamine-2 receptor antagonists; RR - relative risk; DXA - dual X-ray absorptiometry
| Author, publication year | Type of the study | Number of participants | Age | Results |
| Hussain et al., 2018 [3] | Systematic review and meta-analysis of case-control and cohort studies | 1,270,418 | >18 years | RR: 1.26, 95% CI: 1.17-1.35, p<0.00001 |
| Sharara et al., 2013 [4] | Prospective matched controlled study | 58 | 18-50 years | No significant change in serum calcium, phosphorus, PTH, 25-hydroxy vitamin D, osteocalcin, C-terminal cross-linked telopeptides of type I collagen (p>0.05) after 12 months of therapy |
| Hansen et al., 2019 [5] | Prospective multicenter double-blind study | 115 | 45-75 years | No significant differences in changes in markers of bone turnover with PPI use |
| Fraser et al., 2013 [10] | Cohort study | 9,423 | ≥25 years | Adjusted HR for fracture 1.40, 95% CI: 1.11-1.77, p=0.004 |
| Freedberg et al., 2015 [11] | Case-control study | 219,305 | 18-29 years | Adjusted OR for the risk of fracture 1.39, 95% CI: 1.26-1.53 with a dose-response effect (p<0.001 for the trend) |
| Lauppe et al., 2019 [12] | Retrospective cohort study | 26,655 (20,398 general population, 6,257 DXA group (with prior fracture risk factors) | 60-79 | HR: 1.1, 95% CI: 1.0-1.1 in the general population; HR: 1.2, 95% CI: 1.1-1.3 in the DXA group |
| 14,455 (12,755 general population, 1700 DXA group (with prior fracture risk factors) | 80+ | HR: 1.0, 95% CI: 1.0-1.1 in the general population; HR: 0.9, 95% CI: 0.8-1.1 in the DXA group | ||
| Lyu et al., 2020 [13] | Retrospective study in kidney transplant recipients | 1774 (1478 PPI users and 296 H2RA users) | Average age of PPI users: 51.7 years; H2RA users: 45.7 years | Decreasing slope of hip T-score for PPI vs. H2RA users: adjusted OR: 1.3, 95% CI: 0.8-1.9; decreasing slope of spine T-score for PPI vs. H2RA users: adjusted OR: 1.2, 95% CI: 0.8-1.8 (outcomes measured three months after transplant, which remained statistically similar six months after transplant) |
| Mortensen et al., 2020 [14] | Systematic review and meta-analysis | 352,366 (297,488 controls and 54,878 cases) | Average age ≥43 years | OR: 1.29, 95% CI: 1.13-1.47, p<0.001 |
| Ozen et al., 2019 [15] | Longitudinal prospective observational study | 4963 | ≥40 years | Adjusted HR: 0.92, 95% CI: 0.80-1.06 |
| Zirk- Sadowski et al., 2017 [16] | Retrospective cohort study | 172,938 (86,469 treatment group and 86,469 control group) | 60-74 years | Adjusted HR: 1.35, 95% CI: 1.13-1.59 |
| 75-84 years | Adjusted HR: 1.22, 95% CI: 0.96-1.39 | |||
| 85+ years | Adjusted HR: 1.11, 95% CI: 0.86-1.41 | |||
| Itoh et al., 2013 [17] | Randomized controlled trial | 180 | >50 years | % increase in bone mineral density (average±SD), p<0.05 in BP group: 12.4±19.6, in PPI+BP group: 24.6±27.4 |
| % decrease in bone-specific alkaline phosphatase (average±SD), p<0.01 in BP group: 31.9±26.0, in PPI+BP group: 16.4±28.1 |