Proton Pump Inhibitors and Fractures in Adults: A Critical Appraisal and Review of the Literature

Briganti, Silvia Irina; Naciu, Anda Mihaela; Tabacco, Gaia; Cesareo, Roberto; Napoli, Nicola; Trimboli, Pierpaolo; Castellana, Marco; Manfrini, Silvia; Palermo, Andrea

doi:https://doi.org/10.1155/2021/8902367

International Journal of Endocrinology

On this page

Abstract Introduction Methods Conclusions Data Availability Conflicts of Interest Authors’ Contributions References Copyright Related Articles

Review Article | Open Access

Volume 2021 | Article ID 8902367 | https://doi.org/10.1155/2021/8902367

Proton Pump Inhibitors and Fractures in Adults: A Critical Appraisal and Review of the Literature

Silvia Irina Briganti,¹Anda Mihaela Naciu,¹Gaia Tabacco,¹Roberto Cesareo,²Nicola Napoli,¹Pierpaolo Trimboli,³Marco Castellana,⁴Silvia Manfrini,¹and Andrea Palermo¹

Academic Editor: Arturo Bevilacqua

Received02 Apr 2020

Revised30 Dec 2020

Accepted05 Jan 2021

Published15 Jan 2021

Abstract

Despite the large number of patients worldwide being on proton pump inhibitors (PPIs) for acid-related gastrointestinal disorders, uncertainty remains over their long-term safety. Particularly, the potential side effects of these drugs on bone health have been evaluated in the last years. The purpose of our narrative review is to gather and discuss results of clinical studies focusing on the interactions between PPIs and fracture risk. Data generated mainly from nested case-control studies and meta-analysis suggest that long-term/high-dose PPIs users are characterized by an increased risk of fragility fractures, mainly hip fractures. However, in these studies, the PPIs-induced bone impairment is often not adjusted for different confounding variables that could potentially affect bone health, and exposure to PPIs was reported using medical prescriptions without adherence evaluation. The mechanisms of the PPI-related bone damage are still unclear, but impaired micronutrients absorption, hypergastrinemia, and increased secretion of histamine may play a role. Clinicians should pay attention when prescribing PPIs to subjects with a preexistent high risk of fractures and consider antiosteoporotic drugs to manage this additive effect on the bone. However, further studies are needed to clarify PPIs action on the bone.

1. Introduction

Proton pump inhibitors (PPIs) are a class of medications frequently prescribed all around the world. Esomeprazole became one of the most prescribed drugs, in consequence to the high number of diagnosis of gastrointestinal disorders as gastroesophageal reflux disease and peptic ulcers [1]. In the class of PPIs, considering the releases on the pharmaceutical market, it is possible to identify different molecules that share the common capability in reducing gastric acid secretion. PPIs act by irreversibly blocking the hydrogen/potassium adenosine triphosphatase enzyme system (the H + /K + ATPase or the gastric proton pump) of the gastric parietal cells, which make the secretion of H+ ions in the gastric lumen possible [2]. The PPIs are given in an inactive and lipophilic form, which reaches cell cytoplasm crossing cell membranes. In an acid environment, the inactive drug is protonated and rearranges into its active form, linking covalently and irreversibly to the gastric proton pump, deactivating it. The proton pump represents the ideal target for inhibiting acid secretion because of its leading role in creating an acid environment in the stomach; as a result, PPIs are extremely effective in reducing the pain from indigestion and heartburn. However, stomach acids are necessary to absorb calcium, proteins, vitamin B₁₂, drugs, and other nutrients. Therefore, in conditions of prolonged hypochlorhydria, their absorption can result in impairment.

The aim of our narrative review is to gather and discuss results of clinical studies focusing on the interactions between PPIs and fracture risk.

2. Methods

We searched for articles published on PubMed, EMBASE, and the Cochrane Library from inception up to December 2020, according to PRISMA guidelines [3, 4] to identify published original articles and meta-analyses concerning PPIs and bone health. In particular, we searched for articles that investigated the effects of PPIs on fracture risk. The following keywords were searched: proton pump inhibitors or PPIs, lansoprazole, omeprazole, rabeprazole, pantoprazole, esomeprazole, osteoporosis, bone turnover markers, BMD, fracture, falls, osteoblast, and osteoclast.

We searched for articles published in English and those involving human participants. At the same time, we hand-searched the reference lists of the retrieved articles or meta-analyses to identify additional relevant studies. To minimize differences, studies were included if they met the following criteria: (1) those that were cohort studies, case-control studies, cross-sectional studies, randomized controlled studies, or meta-analysis, (2) the exposure of interest was PPIs use and the outcomes were fractures. Exclusion criteria included nonprimary research, review articles, lack of an outcome related to the relationship between PPIs and bone health, abstract-only publications, or non-English language publications. Additional exclusion criteria for full-texts included pediatric population, case reports, and specific conditions recognized to negatively affect bone health, such as stroke, Alzheimer’s, hemodialysis, and kidney transplant. Two investigators (AP and AMN) independently searched papers, screened titles, and abstracts of the retrieved articles, reviewed the full-texts, and selected articles for their inclusion. In case of disagreement, definitive reporting was achieved by mutual consensus.

A total of 1,256 studies were found through PubMed, 1,434 through Embase, and 438 through Cochrane, and after removal of all duplicates, 1,314 articles were analyzed for title and abstract; 1,145 records were excluded (reviews, letters, commentaries, posters, case reports; interventions not in humans, studies including pediatric population, or assessing specific conditions recognized to negatively affect the bone health). The remaining 169 studies were retrieved in full-text, and 25 articles corresponding to 18 case-control studies, 6 meta-analyses, and one retrospective evaluation using an aggregated knowledge-enhanced database (Administration Adverse Event Reporting System Data Mining Set) were finally included in the review (Figure 1). No additional study was retrieved from references of included studies.

3. Potential Mechanisms of PPIs Induced Fracture Risk

PPIs, histamine antagonists, and other antiacid medications have improved the quality of life of patients affected by many gastrointestinal disorders. It has been demonstrated that a chronic use of PPIs is associated with potential adverse drug events, such as hypomagnesaemia, interstitial nephritis, and iron and vitamin B12 malabsorption [5]. During the past 10 years, the relationship between PPIs and bone health (Figure 2) has received attention from many investigators. In particular, PPIs seem to be associated with an increased risk of osteoporotic fractures [6], with a primary potential mechanism involving the physiological effects of chronic acid suppression on calcium, magnesium, and parathyroid hormone (PTH) metabolism [5]. The effect of PPI on bone cells has not been widely described, and available findings are limited and sometimes controversial [7–11]. In general, PPI may cause dose-dependent inhibitory effects on osteoclastic and osteoblastic human cells leading to a kind of low bone turnover syndrome. Therefore, PPI-related bone fragility might be determined by the impairment of the repair mechanisms for bone microfractures that occur daily. However, PPIs use does not appear to determine significant bone quality impairment [12].

3.1. Calcium Absorption

Calcium carbonate, one of the most common dairy calcium salts, is maximally absorbed when administrated together with a meal. Indeed, it is routinely suggested to take calcium carbonate supplements with food [13]. The acidic gastric environment stimulates the release of ionized calcium from insoluble calcium salts. Despite calcium salts precipitate in the small intestine, some calcium ions can be found in solution too. In human subjects with physiological acid secretion, insoluble calcium salts, mainly if taken after a meal, are very well absorbed as soluble calcium salts [14]. Otherwise, in hypo or achlorhydric patients, the absorption of insoluble calcium salts such as calcium carbonate, in fasting conditions, virtually does not occur, while soluble calcium salts such as calcium citrate are still absorbed normally [15]. PPIs, enhancing gastric pH, could interfere with calcium absorption. It can lead to a negative calcium balance with consequent secondary hyperparathyroidism and increased bone loss [5, 16, 17]. Chonan et al. in an animal in vivo evaluation showed that rats on omeprazole therapy presented calcium malabsorption, and the reduction of intestinal pH with dietary lactate prevented the calcium absorption in rats fed with omeprazole [18]. In humans, O’Connell et al. confirmed that, in a population of ≥65 years old women, a daily omeprazole dose of 20 mg significantly reduced fasting absorption of calcium carbonate after only 7 days of treatment [19]. Moreover, impaired calcium absorption has been observed in patients after gastrectomy [20]. However, few studies in this field show controversial results.

Serfaty-Lacrosniere et al. reported that, among young healthy subjects, omeprazole therapy did not reduce the absorption of calcium contained in milk and cheese, probably in consequence to the “meal effect” and to the high bioavailability of calcium salts in these foods [21]. Hansen et al. confirmed that, in a population of postmenopausal women in therapy with omeprazole, after one month of treatment, there were not any observed differences in the absorption of calcium ingested with a meal [22]. Finally, Wright et al. did not find any differences between calcium absorption or urinary calcium excretion on 12 healthy volunteers, with or without a three-day therapy with omeprazole 20 mg twice per day enrolled in a placebo-controlled, double-blind, crossover study [23].

3.1.1. Summary

PPIs increase gastric pH, and most of the evidences seem to confirm that they may negatively affect the calcium absorption. The controversial results of some studies can be related to short-term or low-dose PPIs therapy.

3.2. Hypergastrinemia

More recently, research has focused its attention on PPIs’ relationship with osteoclasts and PTH, the most important calcium-regulating hormone, responsible for maintaining stable calcium concentrations [5]. PTH stimulates bone resorption, increases renal tubular calcium resorption and, through the action of calcitriol, enhances the upper intestine calcium reabsorption [15]. PPIs inhibit HCl secretion in the gastric lumen causing a significant increase in gastric pH, a reduction in somatostatin release from mucosal D cells located in the gastric antrum, and in consequence, an increase in serum gastrin levels. Somatostatin and gastrin act in balance one with the other, so that antiacid medications indirectly cause hypergastrinemia by suppressing somatostatin release. PPIs are excreted by the kidney, so that their compensatory hypergastrinemia appears higher in patients with impaired kidney function in consequence of a reduced drug clearance [24]. Patients in therapy with PPIs present a 2–6-fold increase in serum gastrin in comparison with control subjects [25], especially during the first months of treatment, with a progressive plateau [26]. Enhanced levels of gastrin, responsible for an enterochromaffin-like cells (ECL cells) hyperplasia, induce histamine secretion. Histamine links to receptors localized on mature and precursor osteoclasts promote osteoclastogenesis and bone resorption [27]. However, to date, there are no in vivo human studies that have investigated the impact of hypergastrinemia-induced histamine secretion on bone health. According to this concept, an observational study suggested that the blockage of type 1 histamine receptors on osteoclasts with an H1 receptor antagonist may reduce the risk of hip fractures (adjusted OR: 0.86, 95% CI 0.79–0.93), regardless of PPIs use [28]. Moreover, hypergastrinemia has been shown to have a stimulatory effect on the parathyroid glands. In vivo animal studies demonstrated that omeprazole-induced hypergastrinemia was associated with hyperparathyroidism, with an increase in parathyroid gland volume and weight, and consequent osteopenia [29]. Similar outcomes were obtained in chickens after 5 weeks of omeprazole administration with a resulting hyperplasia and hypertrophy of the parathyroid glands, an increased PTH gene expression and a reduction in femur density [30]. As a proof that all these modifications recognize hypergastrinemia as the major cause, a direct infusion of gastrin increased the weight of the parathyroid glands and reproduced the effect of omeprazole on PTH gene expression in the same animal model [31]. There are only a few in vivo human studies on this topic, and the findings are contrasting [32]. An earlier publication demonstrated that, in subjects with primary hyperparathyroidism, PTH does not affect gastrin levels and that chronic moderate hypercalcemia does not raise serum fasting gastrin, at least in clinical conditions [33]. Instead, Zaniewski and colleagues demonstrated that chronic hypercalcemia of either parathyroid or nonparathyroid origin may elevate serum gastrin concentrations [34]. Moreover, a few evidence support the hypothesis that gastrin may positively regulate parathyroid hormone-related peptide (PTHrP) expression [35].

3.2.1. Summary

PPI-induced hypergastrinemia stimulates histamine and might enhance PTH secretion that may promote osteoclastogenesis and bone resorption. Few in vivo animal and human studies seem to confirm these findings.

3.3. Hypomagnesaemia

PPIs use may be associated with hypomagnesaemia [5]. In particular, a dose response between the PPIs use and development of hypomagnesaemia has been described in literature [36]. Magnesium is an oligoelement involved in bone metabolism both directly and indirectly. Several studies in vitro [37] and in human [38] and animal [39] models have demonstrated that magnesium deficiency reduces osteoblastic activity, detected through the measurement of alkaline phosphatase and osteocalcin, and proliferation. An increase in the number of osteoclasts in conditions of low magnesium levels has also been observed [40]. The imbalance between osteoblastic and osteoclastic differentiation should be likely determined by an enhanced activity of the nitric oxide synthase promoted in the condition of hypomagnesaemia [41]. Furthermore, nitric oxide results involved in bone marrow vasculature modifications, responsible for low magnesium induced-endothelial dysfunction, contribute to the decline of bone mass [42]. In addition to these mechanisms, magnesium deficiency affects bone homeostasis interfering with PTH and vitamin D function [43]. Studies in vitro demonstrated that acute changes in magnesium levels affects PTH secretion (an acute decrease in magnesium concentration increases PTH secretion and vice-versa) [44]. Moreover, in vivo studies have shown that hypomagnesaemia impairs PTH secretion and makes target organs refractory to PTH. PTH signaling involves the adenylate cyclase enzyme, which requires Mg as a cofactor [45]. Similarly, 25-hydroxycholecalciferol-1-hydroxylase requires Mg to promote the hydroxylation of vitamin D intermediates, so that magnesium deficiency could reduce the activity of these two different enzymatic pathways [46]. Finally, hypomagnesaemia promotes oxidative stress, inducing the production of free radicals and cytokines such as TNFα, IL-1s, and IL-6 [47], which stimulate osteoclast activity and differentiation [48], contributing to the imbalance between osteoblasts and osteoclasts [49].

3.3.1. Summary

PPI-induced hypomagnesaemia may determine the imbalance between osteoblasts and osteoclasts, interferes with the hydroxylation of vitamin D intermediates, and makes target organs (renal and bone) resistant to PTH action.

3.4. Increased Falls

Another proposed mechanism that could explain the increase in fracture risk with chronic PPIs use is the increased rate of falls. Indeed, PPIs determine vitamin B12 deficiency in consequence to malabsorption [50]. One prospective cohort study found that patients treated with PPIs were more at risk to have deficient vitamin B12 levels compared to those not treated with a PPIs. Furthermore, in this study, patients treated with PPIs reported numbness of the feet and visual disturbances, a side effect of vitamin B 12 deficiency, which can certainly contribute to an increased risk of falling [51]. A case-control study enrolling 64,399 elderly Swedish patients hospitalized for a fall evidenced that the use of acid suppression drugs caused an increased risk of falling [52]. In addition, Lewis et al. in a large prospective cohort of postmenopausal elderly women found that a continuative therapy with PPIs for 1 year or more was associated with an increased risk of falls and fracture-related hospitalizations. This study also found that patients treated with long-term PPIs had an increased risk of self-reported falling (adjusted OR: 1.51, 95% CI 1.00–2.27) [53].

3.4.1. Summary

PPI-induced vitamin B12 deficiency may lead to an increased rate of falls with the consequent increased risk of fractures.

3.5. PPIs and BMD

Some authors have investigated the relationship between PPIs and BMD changes, but literature offers contrasting results.

A prospective evaluation showed that after 12 months, subjects using PPIs, in particular, esomeprazole, had lower femur neck and total hip BMD T scores [54]. In a large nested case-control study published in 2010, PPIs were associated with a marginal effect on 3-year BMD change at the hip (0.74%, 95% CI (0.01–1.51)) but not at other skeletal sites [55]. In accordance with these previous studies, other cross-sectional evaluations showed that PPIs users had higher rates of osteoporosis at hip than controls [56, 57].

However, the association between PPIs use and hip fracture is probably related to factors partially independent of low bone mass. In fact, some cross-sectional [53, 58] and longitudinal evaluations [58–61] showed that PPIs use does not seem to be associated with BMD loss. These findings are supported by two recent meta-analyses [62, 63].

3.5.1. Summary

PPIs users might not be associated with an increased femoral bone loss, but findings are not conclusive.

3.6. PPIs and Risk of Fractures

The characteristics of the included studies are provided in Table 1. Studies regarding risk of fracture and PPIs included in this review were all case-control studies and have been published from 2006 to 2020. No randomized controlled study was found. A great heterogeneity exists among the studies. Different PPIs were used, and some studies did not specify the type and dosage. Heterogeneity between studies was also noted for age, and the sample size ranged from 261 to 192,028 PPIs users. There was a high variability in the exclusion of comorbidities that can affect bone health. In addition, 8 studies (40% of the included studies) did not adjust the fracture risk for major confounding factors, such as BMD. The minimum length of PPIs exposure was at least one prescription. Great differences in the follow-up time were further sources of heterogeneity.

Focusing on hip fractures, in 2006, Yang et al. conducted a case-control study showing that long-term PPIs therapy exposes users to an increased risk of hip fracture. In particular, the risk significantly increased among patients on long-term and high-dose PPIs (OR: 2.65, 95% CI 1.80–3.90) [64]. In accordance with previous findings, in 2014, Cea Soriano et al. highlighted that PPIs’ use modestly increased risk of hip fracture (OR: 1.09, 95% CI 1.01–1.17) [68]. When compared to H2-receptor antagonists (H2RA), the initiation of PPIs seems to be associated with a higher risk of hip fracture (HR: 1.27, 95% CI 1.09–1.48) [78].

However, evidences reported an increased risk of fractures also at nonfemoral sites [69, 81]. In particular, Vestergaard et al. investigated the effects of one-year therapy with PPIs on fracture risk. They demonstrated that the use of PPIs not only increased the risk of hip fracture (OR: 1.45, 95% CI 1.28–1.65) but also of fractures at spine (OR: 1.60, 95% CI 1.25–2.04) and at any skeletal sites (OR: 1.18, 95% CI 1.12–1.43) [65]. In 2010, Gray performed a nested case-control study on 130,487 women with a follow-up of 7.8 years. After multivariate analysis, the risk for the spine (HR: 1.47, 95% CI 1.18–1.82), lower arm/wrist (HR: 1.26, 95% CI 1.05–1.51), or all site (HR: 1.25, 95% CI 1.15–1.36) fractures resulted increased, but this finding was not observed in hip (HR: 1.00, 95% CI 0.71–1.40) [55].

The PPIs-induced fracture risk seems to be confirmed also after adjusting the analysis for multiple risk factors, including femoral neck bone density and use of bisphosphonates (BP) (HR: 1.40, 95% CI 1.11–1.77). [66]. The impairment of bone health has been shown in both Caucasian [70] and Asian cohorts [67, 75, 77]. In particular, Lee et al. described the increase risk of hip fractures in PPIs users/BP nonusers in comparison with PPIs/BP nonusers in a large cohort of Korean subjects (OR: 1.34, 95% CI 1.24–1.44). However, the risk was not dose and/or drug-dependent in PPIs users/BP nonusers [67]. Very recently, in another cohort of Korean population, Park et al. evaluated 8,903 elderly women suffering osteoporotic fractures and 44,515 matched controls without fractures between 2009 and 2015. Short- and long-term PPIs use showed a positive association with the risk of osteoporotic fracture (OR: 1.3, 95% CI 1.09–1.56 and OR: 1.31, 95% CI 1.23–1.38, respectively), and cumulative dose did not show any influence over fracture risk [75].

PPIs use would negatively affect the fracture risk also in men. In particular, Adams et al. confirmed the relationship between the dose and duration of PPIs use and hip fracture risk in 7,000 nonHispanic Caucasian men (long use—OR: 1.23, 95% CI 1.02–1.48; recent use—OR: 1.22, 95% CI 1.02–1.47) [71].

In the last years, some meta-analyses have investigated the impact of PPIs use on the development of fragility fractures. The authors concluded that PPIs use may be associated with an increased risk of hip [62, 82, 83] and any-site fracture [63, 84, 85].

PPIs seem also to increase the risk of refractures in elderly population. In particular, Brozek et al. analyzed retrospectively the impact of PPIs use on the risk of hip refracture in a population of 31,668 patients who suffered hip fracture between July 2008 and December 2010 excluding antiosteoporotic users. The authors demonstrated that PPIs therapy increased the risk for subsequent hip fracture (OR: 1.58, 95% CI 1.25–2.00), in particular in 70–84-year-old men; however, these findings were not confirmed in case of low dosage (OR: 1.35, 95% CI 0.99–1.82) and short-term therapy (OR: 1.14, 95% CI 0.77–1.69) [80].

In contrast, some authors showed that PPIs do not affect the risk of fracture, regardless of ethnicity, duration of the therapy, and the dose, absolute or cumulative [73, 74, 79]. In particular, in a very recent retrospective investigation, Hoff et al. demonstrated in a Norwegian population of 15,017 women and 13,241 men, aged 50–85 years, that PPIs therapy did not expose to an increased fracture risk in either women (HR: 0.80, 95% CI 0.65–0.98) or men (HR: 1.00, 95% CI 0.69–1.45) [76].

3.6.1. Summary

Most evidences support that long-term high-dosage PPIs users are characterized by the increased risk of fractures.

3.7. Efficacy of Antiresorptive Agents and PPIs

Treatment of osteoporosis is aimed to prevent fragility fractures and to stabilize or increase bone mineral density [86]. It has been demonstrated that PPIs users are more likely to subsequently have osteoporosis therapy than nonusers [72], but it is not clear if PPIs can affect the efficacy of antiosteoporotic therapy in preventing fractures. A small prospective investigation [87] and a post hoc analysis of 3 RCT trials [88] reported that, regardless of PPIs concomitant use, risedronate significantly reduced the risk of new vertebral fractures compared with placebo [88] and increased the BMD [87, 88]. Same findings have been found for the use of teriparatide [89].

As shown by Alhambra et al. and Abrahamsen et al., PPIs use might predict the occurrence of fractures independently of compliance and persistence to BP therapy [90, 91].

Moreover, a meta-analysis published by Yang et al. found that the overall fracture risk of BP and PPIs users versus only BP users was increased [92].

In contrast, there is only one prospective study conducted on osteoporotic patients using concomitant PPIs that has shown a greater increase in lumbar BMD after one year of treatment with alendronate in comparison with alfacalcidiol. However, although the design of study is adequate, the small sample size affects the data interpretation [93].

3.7.1. Summary

Poor and incomplete data do not allow providing clear clinical information on the interaction between PPIs and BPs.

4. Conclusions

Data generated mainly from nested case-control studies and meta-analyses suggest that long-term/high-dose PPIs users are characterized by an increased risk of fragility fractures, mainly hip fractures. However, in these studies, the PPIs-induced bone impairment is often not adjusted for different confounding variables that could potentially affect bone health, and exposure to PPIs was reported using medical prescriptions without adherence evaluation. Impairment of calcium, magnesium, and vitamin B absorbance, hypergastrinemia, an increased secretion of histamine, play an important role in determining the increased fracture risk, although the pathophysiological mechanisms of the PPIs-related bone damage are still unclear.

Physicians should carefully evaluate the risk of fractures in long-term high-dose PPIs users and suggest adequate calcium/vitamin D supplementation. Clinicians should pay attention when prescribing PPIs to subjects with a preexistent high risk of fractures, and they may consider antiosteoporotic drugs to manage this additive effect on the bone. Antiosteoporotic drugs still remain the best option for the management of PPIs users with high risk of fracture.

However, further studies are needed to clarify PPIs’ action on the bone and to estimate the real risk of fracture.

Data Availability

The data supporting this review are from previously reported studies and datasets, which have been cited.

Conflicts of Interest

The authors declare that they have no conflicts of interest.

Authors’ Contributions

Silvia Irina Briganti and Anda Mihaela Naciu contributed equally to this work.

References

L. Aguilera Castro, C. Martín de Argila de Prados, A. Albillos Martínez, and Albillos-Martínez, “Practical considerations in the management of proton-pump inhibitors,” Revista Española de Enfermedades Digestivas, vol. 108, no. 3, 2015.
View at: Publisher Site | Google Scholar
P. Malfertheiner, A. Kandulski, and M. Venerito, “Proton-pump inhibitors: understanding the complications and risks,” Nature Reviews Gastroenterology and Hepatology, vol. 14, no. 12, pp. 697–710, 2017.
View at: Publisher Site | Google Scholar
D. Moher, A. Liberati, J. Tetzlaff, and D. G. Altman, “Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement,” PLoS Medicine, vol. 6, no. 7, p. e1000097, 2009.
View at: Publisher Site | Google Scholar
L. Zorzela, Y. K. Loke, J. P. Ioannidis et al., “PRISMA harms checklist: improving harms reporting in systematic reviews,” BMJ, vol. 352, p. i157, 2016.
View at: Publisher Site | Google Scholar
T. Ito and R. T. Jensen, “Association of long-term proton pump inhibitor therapy with bone fractures and effects on absorption of calcium, vitamin B12, iron, and magnesium,” Current Gastroenterology Reports, vol. 12, no. 6, pp. 448–457, 2010.
View at: Publisher Site | Google Scholar
B. K. S. Thong, S. Ima-Nirwana, and K.-Y. Chin, “Proton pump inhibitors and fracture risk: a review of current evidence and mechanisms involved,” International Journal of Environmental Research and Public Health, vol. 16, no. 9, p. 1571, 2019.
View at: Publisher Site | Google Scholar
M. Prause, C. Seeliger, M. Unger, M. Van Griensven, and A. T. Haug, “Pantoprazole increases cell viability and function of primary human osteoblasts in vitro,” Injury, vol. 45, no. 8, pp. 1156–1164, 2014.
View at: Publisher Site | Google Scholar
M. Prause, C. Seeliger, M. Unger, E. Rosado Balmayor, M. Van Griensven, and A. T. Haug, “Pantoprazole Decreases Cell Viability and Function of Human Osteoclasts in Vitro,” Injury, vol. 45, 2015.
View at: Publisher Site | Google Scholar
J. Costa-Rodrigues, S. Reis, S. Teixeira, S. Lopes, and M. H. Fernandes, “Dose-dependent inhibitory effects of proton pump inhibitors on human osteoclastic and osteoblastic cell activity,” FEBS Journal, vol. 280, no. 20, pp. 5052–5064, 2013.
View at: Publisher Site | Google Scholar
K. Rzeszutek, F. Sarraf, and J. E. Davies, “Proton pump inhibitors control osteoclastic resorption of calcium phosphate implants and stimulate increased local reparative bone growth,” Journal of Craniofacial Surgery, vol. 14, no. 3, pp. 301–307, 2003.
View at: Publisher Site | Google Scholar
A. Sheraly, D. Lickorish, F. Sarraf, and J. Davies, “Use of gastrointestinal proton pump inhibitors to regulate osteoclast- mediated resorption of calcium phosphate cements in vivo,” Current Drug Delivery, vol. 6, no. 2, pp. 192–198, 2009.
View at: Publisher Site | Google Scholar
L. E. Targownik, A. L. Goertzen, Y. Luo, and W. D. Leslie, “Long-term proton pump inhibitor use is not associated with changes in bone strength and structure,” American Journal of Gastroenterology, vol. 112, no. 1, pp. 95–101, 2017.
View at: Publisher Site | Google Scholar
E. T. Champagne, “Low gastric hydrochloric acid secretion and mineral bioavailability,” Advances in Experimental Medicine and Biology, vol. 249, pp. 173–184, 1989.
View at: Publisher Site | Google Scholar
M. S. Sheikh, C. A. Santa Ana, M. J. Nicar, L. R. Schiller, and J. S. Fordtran, “Gastrointestinal absorption of calcium from milk and calcium salts,” New England Journal of Medicine, vol. 317, no. 9, pp. 532–536, 1987.
View at: Publisher Site | Google Scholar
A. Palermo, A. M. Naciu, G. Tabacco et al., “Calcium citrate: from biochemistry and physiology to clinical applications,” Reviews in Endocrine and Metabolic Disorders, vol. 20, no. 3, pp. 353–364, 2019.
View at: Publisher Site | Google Scholar
R. Cesareo, “Effectiveness and safety of calcium and vitamin D treatment for postmenopausal osteoporosis,” Minerva Endocrinologica, vol. 40, no. 3, pp. 231–237, 2015.
View at: Google Scholar
R. Cesareo, A. Falchetti, R. Attanasio et al., “Hypovitaminosis D: is it time to consider the use of calcifediol?” Nutrients, vol. 11, no. 5, p. 1016, 2019.
View at: Publisher Site | Google Scholar
O. Chonan, R. Takahashi, H. Yasui, and M. Watanuki, “Effect of L-lactic acid on calcium absorption in rats fed omeprazole,” Journal of Nutritional Science and Vitaminology, vol. 44, no. 3, pp. 473–481, 1998.
View at: Publisher Site | Google Scholar
M. B. O’Connell, D. M. Madden, A. M. Murray, R. P. Heaney, and L. J. Kerzner, “Effects of proton pump inhibitors on calcium carbonate absorption in women: a randomized crossover trial,” The American Journal of Medicine, vol. 118, no. 7, pp. 778–781, 2005.
View at: Publisher Site | Google Scholar
M. Krause, J. Keller, B. Beil et al., “Calcium gluconate supplementation is effective to balance calcium homeostasis in patients with gastrectomy,” Osteoporosis International, vol. 26, no. 3, pp. 987–995, 2015.
View at: Publisher Site | Google Scholar
C. Serfaty-Lacrosniere, R. J. Wood, D. Voytko et al., “Hypochlorhydria from short-term omeprazole treatment does not inhibit intestinal absorption of calcium, phosphorus, magnesium or zinc from food in humans,” Journal of the American College of Nutrition, vol. 14, no. 4, pp. 364–368, 1995.
View at: Publisher Site | Google Scholar
K. E. Hansen, A. N. Jones, M. J. Lindstrom et al., “Do proton pump inhibitors decrease calcium absorption?” Journal of Bone and Mineral Research, vol. 25, no. 12, pp. 2786–2795, Dec. 2010.
View at: Publisher Site | Google Scholar
M. J. Wright, R. R. Sullivan, E. Gaffney-Stomberg et al., “Inhibiting gastric acid production does not affect intestinal calcium absorption in young, healthy individuals: a randomized, crossover, controlled clinical trial,” Journal of Bone and Mineral Research, vol. 25, no. 10, pp. 2205–2211, 2010.
View at: Publisher Site | Google Scholar
Y.-X. Yang, “Chronic proton pump inihibitor therapy and calcium metabolism,” Current Gastroenterology Reports, vol. 14, no. 6, pp. 473–479, 2012.
View at: Publisher Site | Google Scholar
G. Brunner and W. Creutzfeldt, “Omeprazole in the long-term management of patients with acid-related diseases resistant to ranitidine,” Scandinavian Journal of Gastroenterology, vol. 24, no. sup166, pp. 101–105, 1989.
View at: Publisher Site | Google Scholar
G. Brunner, W. Creutzfeldt, U. Harke, and R. Lamberts, “Therapy with omeprazole in patients with peptic ulcerations resistant to extended high-dose ranitidine treatment,” Digestion, vol. 39, no. 2, pp. 80–90, 1988.
View at: Publisher Site | Google Scholar
M. Biosse-Duplan, B. Baroukh, M. Dy, M.-C. De Vernejoul, and J.-L. Saffar, “Histamine promotes osteoclastogenesis through the differential expression of histamine receptors on osteoclasts and osteoblasts,” The American Journal of Pathology, vol. 174, no. 4, pp. 1426–1434, 2009.
View at: Publisher Site | Google Scholar
B. Abrahamsen and P. Vestergaard, “Proton pump inhibitor use and fracture risk - effect modification by histamine H1 receptor blockade. Observational case-control study using National Prescription Data,” Bone, vol. 57, no. 1, pp. 269–271, 2013.
View at: Publisher Site | Google Scholar
L. Grimelius, H. Johansson, G. Lundqvist, A. Olazabal, J. H. Polak, and A. G. E. Pearse, “The parathyroid glands in experimentally induced hypergastrinemia in the rat,” Scandinavian Journal of Gastroenterology, vol. 12, no. 6, pp. 739–744, 1977.
View at: Publisher Site | Google Scholar
R. Gagnemo-Persson, R. Håkanson, F. Sundler, and P. Persson, “Growth of the parathyroid glands in omeprazole-treated chickens,” Scandinavian Journal of Gastroenterology, vol. 29, no. 6, pp. 493–497, 1994.
View at: Publisher Site | Google Scholar
R. Gagnemo-Persson, A. Samuelsson, R. Håkanson, and P. Persson, “Chicken parathyroid hormone gene expression in response to gastrin, omeprazole, ergocalciferol, and restricted food intake,” Calcified Tissue International, vol. 61, no. 3, pp. 210–215, 1997.
View at: Publisher Site | Google Scholar
K. Mizunashi, Y. Furukawa, K. Katano, and K. Abe, “Effect of omeprazole, an inhibitor of H+, K+-ATPase, on bone resorption in humans,” Calcified Tissue International, vol. 53, no. 1, pp. 21–25, 1993.
View at: Publisher Site | Google Scholar
I. Vantini, “Fasting serum gastrin in primary hyperparathyroidism and in chronic hypercalcemia,” Acta Hepatogastroenterol. (Stuttg)., vol. 26, no. 6, pp. 472–477, 1979.
View at: Google Scholar
M. Zaniewski, P. H. Jordan, B. Yip, J. I. Thornby, and L. E. Mallette, “Serum gastrin level is increased by chronic hypercalcemia of parathyroid or nonparathyroid origin,” Archives of Internal Medicine, vol. 146, no. 3, pp. 478–482, 1986.
View at: Publisher Site | Google Scholar
A. Al Menhali, T. M. Keeley, E. S. Demitrack, and L. C. Samuelson, “Gastrin induces parathyroid hormone-like hormone expression in gastric parietal cells,” American Journal of Physiology-Gastrointestinal and Liver Physiology, vol. 312, no. 6, pp. G649–G657, 2017.
View at: Publisher Site | Google Scholar
T. Srinutta, A. Chewcharat, K. Takkavatakarn et al., “Proton pump inhibitors and hypomagnesemia,” Medicine, vol. 98, no. 44, p. e17788, 2019.
View at: Publisher Site | Google Scholar
R. Schwartz and A. H. Reddi, “Influence of magnesium depletion on matrix-induced endochondral bone formation,” Calcified Tissue International, vol. 29, no. 1, pp. 15–20, 1979.
View at: Publisher Site | Google Scholar
R. K. Rude and H. E. Gruber, “Magnesium deficiency and osteoporosis: animal and human observations,” The Journal of Nutritional Biochemistry, vol. 15, no. 12, pp. 710–716, 2004.
View at: Publisher Site | Google Scholar
A. Creedon, A. Flynn, and K. Cashman, “The effect of moderately and severely restricted dietary magnesium intakes on bone composition and bone metabolism in the rat,” British Journal of Nutrition, vol. 82, no. 1, pp. 63–71, 1999.
View at: Publisher Site | Google Scholar
R. K. Rude, F. R. Singer, and H. E. Gruber, “Skeletal and hormonal effects of magnesium deficiency,” Journal of the American College of Nutrition, vol. 28, no. 2, pp. 131–141, 2009.
View at: Publisher Site | Google Scholar
R. K. Rude, M. E. Kirchen, H. E. Gruber, M. H. Meyer, J. S. Luck, and D. L. Crawford, “Magnesium deficiency-induced osteoporosis in the rat: uncoupling of bone formation and bone resorption,” Magnesium Research, vol. 12, no. 4, pp. 257–267, 1999.
View at: Google Scholar
M. Leidi, F. Dellera, M. Mariotti et al., “Nitric oxide mediates low magnesium inhibition of osteoblast-like cell proliferation,” The Journal of Nutritional Biochemistry, vol. 23, no. 10, pp. 1224–1229, 2012.
View at: Publisher Site | Google Scholar
M. M. Belluci, T. Schoenmaker, C. Rossa-Junior, S. R. Orrico, T. J. de Vries, and V. Everts, “Magnesium deficiency results in an increased formation of osteoclasts,” The Journal of Nutritional Biochemistry, vol. 24, no. 8, pp. 1488–1498, 2013.
View at: Publisher Site | Google Scholar
L. Paunier, “Effect of magnesium on phosphorus and calcium metabolism,” Monatsschrift Kinderheilkunde: Organ der Deutschen Gesellschaft Fur Kinderheilkunde, vol. 140, no. 9 Suppl 1, pp. S17–S20, 1992.
View at: Google Scholar
L. Pironi, “The complex relationship between magnesium and serum parathyroid hormone: a study in patients with chronic intestinal failure,” Magnesium Research, vol. 22, no. 1, pp. 37–43, 2009.
View at: Google Scholar
R. W. Gray, J. L. Omdahl, J. G. Ghazarian, and H. F. DeLuca, “25-Hydroxycholecalciferol-1-hydroxylase. Subcellular location and properties,” The Journal of Biological Chemistry, vol. 247, no. 23, pp. 7528–7532, 1972.
View at: Google Scholar
A. Mazur, J. A. M. Maier, E. Rock, E. Gueux, W. Nowacki, and Y. Rayssiguier, “Magnesium and the inflammatory response: potential physiopathological implications,” Archives of Biochemistry and Biophysics, vol. 458, no. 1, pp. 48–56, 2007.
View at: Publisher Site | Google Scholar
J. C. Baker-LePain, M. C. Nakamura, and N. E. Lane, “Effects of inflammation on bone: an update,” Current Opinion in Rheumatology, vol. 23, no. 4, pp. 389–395, 2011.
View at: Publisher Site | Google Scholar
I. R. Garrett, B. F. Boyce, R. O. Oreffo, L. Bonewald, J. Poser, and G. R. Mundy, “Oxygen-derived free radicals stimulate osteoclastic bone resorption in rodent bone in vitro and in vivo,” Journal of Clinical Investigation, vol. 85, no. 3, pp. 632–639, 1990.
View at: Publisher Site | Google Scholar
S. P. Marcuard, L. Albernaz, and P. G. Khazanie, “Omeprazole therapy causes malabsorption of cyanocobalamin (vitamin B_12),” Annals of Internal Medicine, vol. 120, no. 3, pp. 211–215, 1994.
View at: Publisher Site | Google Scholar
E. Salgueiro, T. Rubio, A. Hidalgo, and G. Manso, “Safety profile of proton pump inhibitors according to the spontaneous reports of suspected adverse reactions,” Int. Journal of Clinical Pharmacology and Therapeutics, vol. 44, no. 11, pp. 548–556, 2006.
View at: Publisher Site | Google Scholar
B. M. Kuschel, L. Laflamme, and J. Möller, “The risk of fall injury in relation to commonly prescribed medications among older people--a Swedish case-control study,” The European Journal of Public Health, vol. 25, no. 3, pp. 527–532, 2015.
View at: Publisher Site | Google Scholar
J. R. Lewis, D. Barre, K. Zhu et al., “Long-term proton pump inhibitor therapy and falls and fractures in elderly women: a prospective cohort study,” Journal of Bone and Mineral Research, vol. 29, no. 11, pp. 2489–2497, 2014.
View at: Publisher Site | Google Scholar
E. Bahtiri, H. Islami, R. Hoxha et al., “Esomeprazole use is independently associated with significant reduction of BMD: 1-year prospective comparative safety study of four proton pump inhibitors,” Journal of Bone and Mineral Metabolism, vol. 34, no. 5, pp. 571–579, 2016.
View at: Publisher Site | Google Scholar
S. L. Gray, “Proton pump inhibitor use, hip fracture, and change in bone mineral density in postmenopausal women,” Archives of Internal Medicine, vol. 170, no. 9, pp. 765–771, 2010.
View at: Publisher Site | Google Scholar
A. Arj, M. Razavi Zade, M. Yavari, H. Akbari, B. Zamani, and Z. Asemi, “Proton pump inhibitors use and change in bone mineral density,” International Journal of Rheumatic Diseases, vol. 19, no. 9, pp. 864–868, 2016.
View at: Publisher Site | Google Scholar
M. R. Fattahi, R. Niknam, M. Shams et al., “The association between prolonged proton pump inhibitors use and bone mineral density,” Risk Management and Healthcare Policy, vol. 12, pp. 349–355, 2019.
View at: Publisher Site | Google Scholar
L. E. Targownik, L. M. Lix, S. Leung, and W. D. Leslie, “Proton-pump inhibitor use is not associated with osteoporosis or accelerated bone mineral density loss,” Gastroenterology, vol. 138, no. 3, pp. 896–904, 2010.
View at: Publisher Site | Google Scholar
K. E. Hansen, J. W. Nieves, S. Nudurupati, D. C. Metz, and M. C. Perez, “Dexlansoprazole and esomeprazole do not affect bone homeostasis in healthy postmenopausal women,” Gastroenterology, vol. 156, no. 4, pp. 926–934, 2019.
View at: Publisher Site | Google Scholar
D. H. Solomon, S. J. Diem, K. Ruppert et al., “Bone mineral density changes among women initiating proton pump inhibitors or H2 receptor antagonists: a SWAN cohort study,” Journal of Bone and Mineral Research, vol. 30, no. 2, pp. 232–239, 2015.
View at: Publisher Site | Google Scholar
E. W. Yu, T. Blackwell, K. E. Ensrud et al., “Acid-suppressive medications and risk of bone loss and fracture in older adults,” Calcified Tissue International, vol. 83, no. 4, pp. 251–259, 2008.
View at: Publisher Site | Google Scholar
Y. Nassar and S. Richter, “Proton-pump inhibitor use and fracture risk: an updated systematic review and meta-analysis,” Journal of Bone Metabolism, vol. 25, no. 3, p. 141, 2018.
View at: Publisher Site | Google Scholar
J. Liu, X. Li, L. Fan et al., “Proton pump inhibitors therapy and risk of bone diseases: an update meta-analysis,” Life Sciences, vol. 218, pp. 213–223, 2019.
View at: Publisher Site | Google Scholar
Y.-X. Yang, J. D. Lewis, S. Epstein, and D. C. Metz, “Long-term proton pump inhibitor therapy and risk of hip fracture,” JAMA, vol. 296, no. 24, pp. 2947–2953, 2006.
View at: Publisher Site | Google Scholar
P. Vestergaard, L. Rejnmark, and L. Mosekilde, Proton Pump Inhibitors , Histamine H 2 Receptor Antagonists , and Other Antacid Medications and the Risk of Fracture, Springer, Berlin, Germany, 2006, –83.
View at: Publisher Site
L. E. Targownik, A. Papaioannou, and J. D. Adachi, “The effect of proton pump inhibitors on fracture risk: report from the Canadian Multicenter Osteoporosis Study,” Osteoporosis International, vol. 24, no. 4, pp. 1161–1168, 2013.
View at: Publisher Site | Google Scholar
J. Lee, K. Youn, J. L. Dongyoon, K. H. Song, and B. Park, “A population-based case – control study : proton pump inhibition and risk of hip fracture by use of bisphosphonate,” Journal of Gastroenterology and Hepatology, vol. 48, 2013.
View at: Publisher Site | Google Scholar
L. Cea Soriano, A. Ruigómez, S. Johansson, and L. A. García Rodríguez, “Study of the association between hip fracture and acid-suppressive drug use in a UK primary care setting,” Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy, vol. 34, no. 6, pp. 570–581, 2014.
View at: Publisher Site | Google Scholar
J. Ding, D. A. Heller, F. M. Ahern, and T. V. Brown, “The relationship between proton pump inhibitor adherence and fracture risk in the elderly,” Calcified Tissue International, vol. 94, no. 6, pp. 597–607, 2014.
View at: Publisher Site | Google Scholar
L. M. E. Moberg, P. M. Nilsson, G. Samsioe, and C. Borgfeldt, “Use of proton pump inhibitors (PPI) and history of earlier fracture are independent risk factors for fracture in postmenopausal women. The WHILA study,” Maturitas, vol. 78, no. 4, pp. 310–315, 2014.
View at: Publisher Site | Google Scholar
A. L. Adams, M. H. Black, J. L. Zhang, J. M. Shi, and S. J. Jacobsen, “Proton-pump inhibitor use and hip fractures in men: a population-based case-control study,” Annals of Epidemiology, vol. 24, no. 4, pp. 286–290, 2014.
View at: Publisher Site | Google Scholar
M. M. C. van der Hoorn, S. E. Tett, O. J. de Vries, A. J. Dobson, and G. M. E. E. Peeters, “The effect of dose and type of proton pump inhibitor use on risk of fractures and osteoporosis treatment in older Australian women: a prospective cohort study,” Bone, vol. 81, pp. 675–682, 2015.
View at: Publisher Site | Google Scholar
S.-W. Lai, C.-H. Lin, C.-L. Lin, and K.-F. Liao, “Proton pump inhibitors therapy and the risk of hip fracture in older people in Taiwan,” European Geriatric Medicine, vol. 9, no. 2, pp. 169–174, 2018.
View at: Publisher Site | Google Scholar
B. N. Harding, N. S. Weiss, R. L. Walker, E. B. Larson, and S. Dublin, “Proton pump inhibitor use and the risk of fractures among an older adult cohort,” Pharmacoepidemiology and Drug Safety, vol. 27, no. 6, pp. 596–603, 2018.
View at: Publisher Site | Google Scholar
J.-H. Park, Y.-M. Song, J.-H. Jung, and K. Han, “Comparative analysis of the risk of osteoporotic fractures with proton pump inhibitor use and histamine-2 receptor antagonist therapy in elderly women: a nationwide population-based nested case-control study,” Bone, vol. 135, p. 115306, 2020.
View at: Publisher Site | Google Scholar
M. Hoff, E. Skovlund, S. Skurtveit et al., “Proton pump inhibitors and fracture risk. The HUNT study, Norway,” Osteoporosis International, vol. 31, no. 1, pp. 109–118, 2020.
View at: Publisher Site | Google Scholar
J.-H. Park, J. Lee, S.-Y. Yu et al., “Comparing proton pump inhibitors with histamin-2 receptor blockers regarding the risk of osteoporotic fractures: a nested case-control study of more than 350,000 Korean patients with GERD and peptic ulcer disease,” BMC Geriatrics, vol. 20, no. 1, 2020.
View at: Publisher Site | Google Scholar
J. Wei, A. T. Chan, C. Zeng et al., “Association between proton pump inhibitors use and risk of hip fracture: a general population-based cohort study,” Bone, vol. 139, p. 115502, 2020.
View at: Publisher Site | Google Scholar
C. Reyes, F. Formiga, M. Coderch et al., “Use of proton pump inhibitors and risk of fragility hip fracture in a Mediterranean region,” Bone, vol. 52, no. 2, pp. 557–561, 2013.
View at: Publisher Site | Google Scholar
W. Brozek, B. Reichardt, J. Zwerina, H. P. Dimai, K. Klaushofer, and E. Zwettler, “Higher dose but not low dose proton pump inhibitors are associated with increased risk of subsequent hip fractures after first hip fracture: a nationwide observational cohort study,” Bone Reports, vol. 10, p. 100204, 2019.
View at: Publisher Site | Google Scholar
L. Wang, M. Li, Y. Cao et al., “Proton pump inhibitors and the risk for fracture at specific sites: data mining of the FDA adverse event reporting system,” Scientific Reports, vol. 7, no. 1, p. 5527, 2017.
View at: Publisher Site | Google Scholar
S. Hussain, A. N. Siddiqui, A. Habib, M. S. Hussain, and A. K. Najmi, “Proton pump inhibitors’ use and risk of hip fracture: a systematic review and meta-analysis,” Rheumatology International, vol. 38, no. 11, p. 1999, 2018.
View at: Publisher Site | Google Scholar
T. N. Poly, M. M. Islam, H.-C. Yang, C. C. Wu, and Y.-C. Li, “Proton pump inhibitors and risk of hip fracture: a meta-analysis of observational studies,” Osteoporosis International, vol. 30, no. 1, pp. 103–114, 2019.
View at: Publisher Site | Google Scholar
B. Zhou, Y. Huang, H. Li, W. Sun, and J. Liu, “Proton-pump inhibitors and risk of fractures: an update meta-analysis,” Osteoporosis International, vol. 27, no. 1, pp. 339–347, 2016.
View at: Publisher Site | Google Scholar
C. S. Kwok, J. K.-Y. Yeong, and Y. K. Loke, “Meta-analysis: risk of fractures with acid-suppressing medication,” Bone, vol. 48, no. 4, pp. 768–776, 2011.
View at: Publisher Site | Google Scholar
F. Vescini, R. Attanasio, A. Balestrieri et al., “Italian association of clinical endocrinologists (AME) position statement: drug therapy of osteoporosis,” Journal of Endocrinological Investigation, vol. 39, no. 7, pp. 807–834, 2016.
View at: Publisher Site | Google Scholar
M. Tanaka, S. Itoh, T. Yoshioka, and K. Yamashita, “The therapeutic effectiveness of the coadministration of weekly risedronate and proton pump inhibitor in osteoporosis treatment,” Journal of Osteoporosis, vol. 2014, Article ID 607145, 1 page, 2014.
View at: Publisher Site | Google Scholar
C. Roux, J. L. Goldstein, X. Zhou, A. Klemes, and R. Lindsay, “Vertebral fracture efficacy during risedronate therapy in patients using proton pump inhibitors,” Osteoporosis International, vol. 23, no. 1, pp. 277–284, 2012.
View at: Publisher Site | Google Scholar
D. L. Kendler, F. Marin, P. Geusens et al., “Psychotropic medications and proton pump inhibitors and the risk of fractures in the teriparatide versus risedronate VERO clinical trial,” Bone, vol. 130, no. Jan, p. 115113, 2020.
View at: Publisher Site | Google Scholar
D. Prieto-Alhambra, A. Pagès-Castellà, G. Wallace et al., “Predictors of fracture while on treatment with oral bisphosphonates: a population-based cohort study,” Journal of Bone and Mineral Research, vol. 29, no. 1, pp. 268–274, 2014.
View at: Publisher Site | Google Scholar
B. Abrahamsen, P. Eiken, and R. Eastell, “Proton pump inhibitor use and the antifracture efficacy of alendronate,” Archives of Internal Medicine, vol. 171, no. 11, pp. 998–1004, 2011.
View at: Publisher Site | Google Scholar
S. D. Yang, Q Chen, H. K Wei et al., “Bone fracture and the interaction between bisphosphonates and proton pump inhibitors: a meta-analysis,” International Journal of Clinical and Experimental Medicine, vol. 8, no. 4, pp. 4899–4910, 2015.
View at: Google Scholar
D. Asaoka, A. Nagahara, M. Hojo et al., “Efficacy of alfacalcidol and alendronate on lumbar bone mineral density in osteoporotic patients using proton pump inhibitors,” Biomedical Reports, vol. 5, no. 2, pp. 165–170, 2016.
View at: Publisher Site | Google Scholar

Copyright

Copyright © 2021 Silvia Irina Briganti et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

PDF Download Citation

Download other formats

Order printed copies

Views

3221

Downloads

1333

Citations