Original Full Length ArticleUse of proton pump inhibitors is associated with lower trabecular bone density in older individuals
Introduction
Proton pump inhibitors (PPIs) are potent gastric acid suppressing drugs with proven efficacy both in the prevention and treatment of peptic ulcers, gastroesophageal reflux disease, and erosive esophagitis [1], [2]. Since their introduction in the 1980s, PPIs have been one of the most prescribed classes of drugs worldwide due to their high effectiveness in acid-related conditions, compared to histamine receptor antagonists [3].
In the last two decades we have observed a marked increase in PPI use, especially among older persons, supported by the availability of both over-the-counter and generic formulations [4].
Despite the evident clinical benefits, recent epidemiological studies underline an often inappropriate PPI prescription for up to 50–80% of patients admitted to acute wards of geriatric and internal medicine [5], [6], [7], [8], [9], [10].
There is growing evidence that high PPI exposure and/or an inappropriate treatment period are accompanied by a variety of relevant clinical adverse events. This is particularly evident in chronic PPI users and vulnerable classes of individuals such as the elderly. In this population the chronic acid suppression induced by PPIs has been associated with an increased risk of community-acquired pneumonia [11], [12], [13], [14], C. difficile infections [15], [16], [17], and malnutrition [18] including hypomagnesemia [19]. In addition, PPIs share common metabolic pathways with several classes of medications such as nonsteroidal anti-inflammatory, antiplatelet and bisphosphonates, whose effectiveness might be reduced by PPI use [20], [21]. More recently, in older patients discharged from acute care hospitals, the use of high doses of PPIs has been associated with an increased risk of 1-year mortality [22].
The Food and Drug Administration has recently reported in a safety communication the evidence of a worrying increased risk of fractures induced by chronic PPI treatment [23]. A meta-analysis of 11 observational studies showed a mild increased risk of hip and vertebral fractures in PPI users of both sexes, compared to H2RA users [24]. Interestingly, the results were stronger in older participants and confirmed in a recent meta-analysis [24], [25].
Age-related changes in bone mass, bone mineral density (BMD), bone geometry and architecture, cortical bone thickness and trabecular porosity, negatively affect the bone strength, one of the most important determinants of fractures. Bone remodelling is faster and significantly more evident in trabecular bone and as far as we know, changes in trabecular bone occur early in the pathway to full blown osteoporosis [26], [27]. Use of PPIs might exacerbate the age related modifications in bone density and strength.
Despite the increasing evidence of a relationship between PPI and bone fractures, few studies have explored the hypothesis that PPI use may be associated with deteriorated bone density and structural geometry.
The aim of the study is to characterize the relationship between PPI use and parameters of bone mineral density and geometry as well as markers of bone strength in older community dwelling persons.
Section snippets
Study population
InCHIANTI is an epidemiological study of risk factors for mobility disability in the elderly, designed by the Laboratory of Clinical Epidemiology of the Italian Research Council of Aging (Florence), and conducted on a representative sample of a population living in Greve in Chianti and Bagno a Ripoli, two small towns of Tuscany, Italy. The study design and data collection have been described elsewhere [26], [27], [28], [29]. Of the whole study population, 1260 subjects were 65 years old or
Results
The characteristics of the participants were presented for the entire sample and participants were stratified according to PPI use. The prevalence of PPI use among the InChianti community dwelling older persons was 3.4% (22 women and 14 men). The majority of persons were on PPI (N = 25; 70%) due to gastro-protection during NSAIDs or chronic aspirin treatment; the remaining 30% (N = 11) were on PPI because of peptic gastro-intestinal ulcer (Table 1). Since the neither interaction terms sex*PPI
Discussion
Our data show a negative association between PPI use and trabecular bone mineral density in a small sample of community dwelling older persons. These findings support the hypothesis of a possible direct effect of PPIs on bone mineral metabolism.
This is the first study testing the relationship between PPI use and parameters of bone mass and geometry in older persons. Several studies have shown a significant association between PPI use and bone fractures [24], [25], although the number of
Authors' roles
Study design was performed by M.M. and F.L.; study conduct, by F.L., S.B., A.C., F.L. and L.F.; data collection, by F.L., S.B., A.C. and F.L.; data analysis, by M.M. and F.L.; data interpretation, by G.C., M.M., F.L., C.C., C.R., A.N. and T.M.; drafting the article, by M.M., F.D. and G.B.; revising the article content, by M.M. and L.F.; and approving the final version of the article, by M.M., G.C., T.M., S.B., A.C., C.R., F.L. and L.F.
Disclosure
All authors state that they have no conflicts of interest.
Acknowledgments
The InCHIANTI Study was supported as a “targeted project” (ICS 110.1/RS97.71) by the Italian Ministry of Health and in part by the US National Institute on Aging (Contracts N01-AG-916413 and N01-AG-821336), and by the Intramural Research Program of the US National Institute on Aging (Contracts 263 MD 9164 13 and 263 MD 821336) and by grant RF-2010-2312659 from the Italian Ministry of Health and Emilia Romagna Region. None of the sponsoring institutions interfered with the collection, analysis,
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