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Carugo S, Vescini F, Giusti A, Mauro GL, Tafaro L, Festuccia F, Muraca L, Menè P, Rossini M. The essential role of combined calcium and vitamin D supplementation in the osteoporosis scenario in italy: Expert opinion paper. Arch Osteoporos 2024; 19:99. [PMID: 39438361 PMCID: PMC11496317 DOI: 10.1007/s11657-024-01451-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/31/2024] [Accepted: 09/23/2024] [Indexed: 10/25/2024]
Abstract
An Italian multidisciplinary working group discussed the current Italian scenario of osteoporosis management during a meeting and highlighted the essential role of calcium and vitamin D supplementation in the prevention of fragility fractures. PURPOSE This paper aims to review and discuss data on calcium and vitamin D requirements and the role of combined calcium and vitamin D supplementation in the treatment of patients with osteoporosis. METHODS The discussion of the experts covered literature data on calcium and vitamin D supplementation, gaps in the diagnosis and treatment of osteoporosis, and the role of the primary care physician in identifying and treating patients with osteoporosis. Articles for consideration were identified through PubMed searches using different combinations of pertinent keywords. RESULTS The discussion highlighted that insufficient calcium or vitamin D intake increases the risk of fragility fractures. The experts also drew attention to the essential role of calcium and vitamin D supplementation in achieving an anti-fracture effect and supporting the efficacy of anti-osteoporotic agents without increasing nephrolithiasis and cardiovascular risks. In addition, the discussion underlined the role of the primary care physician in the initial clinical approach to patients with osteoporosis. CONCLUSIONS The experts believe that efficient treatment for patients with osteoporosis should include calcium and vitamin D supplementation to achieve adequate levels that are able to inhibit the parathyroid hormone and bone resorption.
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Affiliation(s)
- Stefano Carugo
- Department of Clinical Sciences and Community Health, University of Milan, 20122, Milan, Italy
- Department of Cardio-Thoracic-Vascular Diseases, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Fabio Vescini
- Endocrinology Unit University Hospital of Udine, Udine, Italy
| | - Andrea Giusti
- Division of Internal Medicine, Department of Medicine & Cardiology, "Villa Scassi" Hospital, Genoa, Italy, ASL3, 16132, Genoa, Italy
| | - Giulia Letizia Mauro
- Department of Precision Medicine in the Medical, Surgical and Critical Care Area (Me.Pre.C.C.), University of Palermo, 90127, Palermo, Italy
| | - Laura Tafaro
- Department of Clinical and Molecular Medicine, Sapienza University of Rome, Sant'Andrea Hospital, Rome, Italy
| | | | - Lucia Muraca
- Department of Primary Care, ASP Catanzaro, 88100, Catanzaro, Italy
| | - Paolo Menè
- Division of Nephrology, Sapienza University of Rome, Sant'Andrea University Hospital, Rome, Italy
| | - Maurizio Rossini
- Department of Medicine, Rheumatology Unit, University of Verona, Verona, Italy.
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Zhang Y, Liu M, Zhu Z, Chen H. Proton pump inhibitors use is associated with a higher prevalence of kidney stones: NHANES 2007-2018. BMC Public Health 2024; 24:1215. [PMID: 38698372 PMCID: PMC11067170 DOI: 10.1186/s12889-024-18710-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2023] [Accepted: 04/24/2024] [Indexed: 05/05/2024] Open
Abstract
BACKGROUND Proton pump inhibitors (PPIs) are widely used throughout the world as an effective gastrointestinal drug. Nevertheless, according to the existing literature, PPIs can reduce the excretion of magnesium, calcium and other components in urine, which may promote the formation of kidney stones. We used the National Health and Nutrition Examination Survey (NHANES) database to further investigate the association between the use of PPIs and the prevalence of kidney stones. METHODS We performed a cross-sectional analysis using data from 2007 to 2018 NHANES. PPIs use information of 29,910 participants was obtained by using prescription medications in the preceding month, and kidney stones were presented by a standard questionnaire. Multiple regression analysis and stratified analysis were used to estimate the association between PPIs use and kidney stones after an adjustment for potential confounders. RESULTS The multiple logistic regression indicated that the PPIs exposure group (P1) had a significantly higher risk of nephrolithiasis than the PPIs non-exposure group (P0) in Model 3 (OR 1.24, 95% CI 1.10-1.39, P < 0.001). The stratified analyses indicated there were significant statistical differences between PPIs use and kidney stones among females (OR 1.36, 95% CI 1.15-1.62, P < 0.001), non-Hispanic whites (OR 1.27, 95% CI 1.09-1.48, P = 0.002), individuals with an education level than 11th grade (OR 1.41, 95% CI 1.13-1.76, P = 0.002) and individuals with an annual family income of $0 to $19,999 (OR 1.32, 95% CI 1.06-1.65, P = 0.014) and $20,000 to $44,999 (OR 1.25, 95% CI 1.02-1.54, P = 0.033) in Model 3. CONCLUSIONS Our study revealed that PPIs use is associated with a higher prevalence of kidney stones for the US population, primarily among women, non-Hispanic whites, individuals with low education levels and individuals with low household income levels. Further studies are required to confirm our findings.
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Affiliation(s)
- Youjie Zhang
- Department of Urology, Xiangya Hospital, Central South University, Changsha, 410008, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
| | - Minghui Liu
- Department of Urology, Xiangya Hospital, Central South University, Changsha, 410008, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
| | - Zewu Zhu
- Department of Urology, Xiangya Hospital, Central South University, Changsha, 410008, China.
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China.
| | - Hequn Chen
- Department of Urology, Xiangya Hospital, Central South University, Changsha, 410008, China.
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China.
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Wu KC, Cao S, Weaver CM, King NJ, Patel S, Kim TY, Black DM, Kingman H, Shafer MM, Rogers SJ, Stewart L, Carter JT, Posselt AM, Schafer AL. Intestinal Calcium Absorption Decreases After Laparoscopic Sleeve Gastrectomy Despite Optimization of Vitamin D Status. J Clin Endocrinol Metab 2023; 108:351-360. [PMID: 36196648 PMCID: PMC10091486 DOI: 10.1210/clinem/dgac579] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/08/2022] [Revised: 08/30/2022] [Indexed: 01/20/2023]
Abstract
CONTEXT Laparoscopic sleeve gastrectomy (LSG), now the most commonly performed bariatric operation, is a highly effective treatment for obesity. While Roux-en-Y gastric bypass is known to impair intestinal fractional calcium absorption (FCA) and negatively affect bone metabolism, LSG's effects on calcium homeostasis and bone health have not been well characterized. OBJECTIVE We determined the effect of LSG on FCA, while maintaining robust 25-hydroxyvitamin D (25OHD) levels and recommended calcium intake. DESIGN, SETTING, PARTICIPANTS Prospective pre-post observational cohort study of 35 women and men with severe obesity undergoing LSG. MAIN OUTCOMES FCA was measured preoperatively and 6 months postoperatively with a gold-standard dual stable isotope method. Other measures included calciotropic hormones, bone turnover markers, and bone mineral density (BMD) by dual-energy X-ray absorptiometry and quantitative computed tomography. RESULTS Mean ± SD FCA decreased from 31.4 ± 15.4% preoperatively to 16.1 ± 12.3% postoperatively (P < 0.01), while median (interquartile range) 25OHD levels were 39 (32-46) ng/mL and 36 (30-46) ng/mL, respectively. Concurrently, median 1,25-dihydroxyvitamin D level increased from 60 (50-82) pg/mL to 86 (72-107) pg/mL (P < 0.01), without significant changes in parathyroid hormone or 24-hour urinary calcium levels. Bone turnover marker levels increased substantially, and areal BMD decreased at the proximal femur. Those with lower postoperative FCA had greater areal BMD loss at the total hip (ρ = 0.45, P < 0.01). CONCLUSIONS FCA decreases after LSG, with a concurrent rise in bone turnover marker levels and decline in BMD, despite robust 25OHD levels and with recommended calcium intake. Decline in FCA could contribute to negative skeletal effects following LSG.
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Affiliation(s)
- Karin C Wu
- Department of Medicine, University of California San Francisco, San Francisco, CA 94143, USA
- Endocrine Research Unit, San Francisco Veterans Affairs Health Care System, San Francisco, CA 94121, USA
| | - Sisi Cao
- Department of Human Sciences, The Ohio State University, Columbus, OH 43210, USA
| | - Connie M Weaver
- Department of Exercise and Nutritional Sciences, San Diego State University, San Diego, CA 92182, USA
| | - Nicole J King
- Endocrine Research Unit, San Francisco Veterans Affairs Health Care System, San Francisco, CA 94121, USA
| | - Sheena Patel
- California Pacific Medical Center Research Institute, San Francisco, CA 94107, USA
| | - Tiffany Y Kim
- Department of Medicine, University of California San Francisco, San Francisco, CA 94143, USA
- Endocrine Research Unit, San Francisco Veterans Affairs Health Care System, San Francisco, CA 94121, USA
| | - Dennis M Black
- Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, CA 94143, USA
| | - Hillary Kingman
- Endocrine Research Unit, San Francisco Veterans Affairs Health Care System, San Francisco, CA 94121, USA
| | - Martin M Shafer
- Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI 53705, USA
| | - Stanley J Rogers
- Department of Surgery, University of California San Francisco, San Francisco, CA 94143, USA
| | - Lygia Stewart
- Department of Surgery, University of California San Francisco, San Francisco, CA 94143, USA
- Surgical Services, San Francisco Veterans Affairs Health Care System, San Francisco, CA 94121, USA
| | - Jonathan T Carter
- Department of Surgery, University of California San Francisco, San Francisco, CA 94143, USA
| | - Andrew M Posselt
- Department of Surgery, University of California San Francisco, San Francisco, CA 94143, USA
| | - Anne L Schafer
- Department of Medicine, University of California San Francisco, San Francisco, CA 94143, USA
- Endocrine Research Unit, San Francisco Veterans Affairs Health Care System, San Francisco, CA 94121, USA
- Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, CA 94143, USA
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Hussain MS, Mazumder T. Long-term use of proton pump inhibitors adversely affects minerals and vitamin metabolism, bone turnover, bone mass, and bone strength. J Basic Clin Physiol Pharmacol 2021; 33:567-579. [PMID: 34687598 DOI: 10.1515/jbcpp-2021-0203] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2021] [Accepted: 10/01/2021] [Indexed: 11/15/2022]
Abstract
Notwithstanding, proton pump inhibitors (PPIs) are one of the most excellent options for different anti-secretory therapy in terms of improved symptomatic outcomes, numerous epidemiological and cohort studies provide evidence of an association between long-term proton PPIs use and increased fracture risk among users. The present attempt aimed to summarize the effect of long-term use of PPIs on musculoskeletal systems by considering the recent claims of different research groups to understand the risk of osteopenia and osteoporosis and to determine the risk factors associated with these complications. We extracted data from various systematic reviews and meta-analyses, cross-sectional studies, prospective studies, case-control studies, cohort studies, and in-vivo and in-vitro studies to observe the consequence of long-term PPIs uses over the patient's bone health. Recent findings suggested that long-term use of PPIs plays an introductory and cabalistic role in the development of osteoporosis mostly hip fractures by disturbing numerous biological pathways and thus able to set up a link between over-prescription of PPIs and bone loss. Frequent administration of PPIs is associated with a significantly worse outcome to bone mineral density (BMD) profile and produce a negative impression on bone health. Since, there are limited data to determine the association of PPIs use and change in BMD, recommending further studies to find out this dissertation.
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Affiliation(s)
- Md Saddam Hussain
- Department of Pharmacy, Faculty of Science, Noakhali Science and Technology University, Noakhali, Bangladesh
| | - Tanoy Mazumder
- Department of Pharmacy, Faculty of Science, Noakhali Science and Technology University, Noakhali, Bangladesh
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Kose E, Wakabayashi H, Yasuno N. Polypharmacy and Malnutrition Management of Elderly Perioperative Patients with Cancer: A Systematic Review. Nutrients 2021; 13:1961. [PMID: 34200493 PMCID: PMC8227653 DOI: 10.3390/nu13061961] [Citation(s) in RCA: 29] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2021] [Revised: 06/02/2021] [Accepted: 06/03/2021] [Indexed: 12/11/2022] Open
Abstract
Malnutrition, which commonly occurs in perioperative patients with cancer, leads to decreased muscle mass, hypoalbuminemia, and edema, thereby increasing the patient's risk of various complications. Thus, the nutritional management of perioperative patients with cancer should be focused on to ensure that surgical treatment is safe and effective, postoperative complications are prevented, and mortality is reduced. Pathophysiological and drug-induced factors in elderly patients with cancer are associated with the risk of developing malnutrition. Pathophysiological factors include the effects of tumors, cachexia, and anorexia of aging. Metabolic changes, such as inflammation, excess catabolism, and anabolic resistance in patients with tumor-induced cancer alter the body's ability to use essential nutrients. Drug-induced factors include the side effects of anticancer drugs and polypharmacy. Drug-drug, drug-disease, drug-nutrient, and drug-food interactions can significantly affect the patient's nutritional status. Furthermore, malnutrition may affect pharmacokinetics and pharmacodynamics, potentiate drug effects, and cause side effects. This review outlines polypharmacy and malnutrition, the impact of malnutrition on drug efficacy, drug-nutrient and drug-food interactions, and intervention effects on polypharmacy or cancer cachexia in elderly perioperative patients with cancer.
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Affiliation(s)
- Eiji Kose
- Department of Pharmacy, Teikyo University School of Medicine University Hospital, 2-11-1 Kaga, Itabashi City, Tokyo 173-8606, Japan;
| | - Hidetaka Wakabayashi
- Department of Rehabilitation Medicine, Tokyo Women’s Medical University Hospital, 8-1 Kawadacho, Shinjuku City, Tokyo 162-8666, Japan;
| | - Nobuhiro Yasuno
- Department of Pharmacy, Teikyo University School of Medicine University Hospital, 2-11-1 Kaga, Itabashi City, Tokyo 173-8606, Japan;
- Laboratory of Hospital Pharmacy, School of Pharmacy, Teikyo University, 2-11-1 Kaga, Itabashi City, Tokyo 173-8605, Japan
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Is drug consumption correlated with benign paroxysmal positional vertigo (BPPV) recurrence? Eur Arch Otorhinolaryngol 2020; 277:1609-1616. [DOI: 10.1007/s00405-020-05855-6] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2019] [Accepted: 02/06/2020] [Indexed: 10/25/2022]
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Bosnjak T, Solberg R, Hemati PD, Jafari A, Kassem M, Johansen HT. Lansoprazole inhibits the cysteine protease legumain by binding to the active site. Basic Clin Pharmacol Toxicol 2019; 125:89-99. [PMID: 30916878 DOI: 10.1111/bcpt.13230] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2018] [Accepted: 02/20/2019] [Indexed: 12/13/2022]
Abstract
Proton pump inhibitors (PPIs) are prodrugs used in the treatment of peptic ulcer diseases. Once activated by acidic pH, the PPIs subsequently inhibit the secretion of gastric acid by covalently forming disulphide bonds with the SH groups of the parietal proton pump, that is the H+ /K+ -ATPase. Long-term use of PPIs has been associated with numerous adverse effects, including bone fractures. Considering the mechanism of activation, PPIs could also be active in acidic micro-environments such as in lysosomes, tumours and bone resorption sites. We suggested that the SH group in the active site of cysteine proteases could be susceptible for inhibition by PPIs. In this study, the inhibition by lansoprazole was shown on the cysteine proteases legumain and cathepsin B by incubating purified proteases or cell lysates with lansoprazole at different concentrations and pH conditions. The mechanism of legumain inhibition was shown to be a direct interaction of lansoprazole with the SH group in the active site, and thus blocking binding of the legumain-selective activity-based probe MP-L01. Lansoprazole was also shown to inhibit both legumain and cathepsin B in various cell models like HEK293, monoclonal legumain over-expressing HEK293 cells (M38L) and RAW264.7 macrophages, but not in human bone marrow-derived skeletal (mesenchymal) stem cells (hBMSC-TERT). During hBMSC-TERT differentiation to osteoblasts, lansoprazole inhibited legumain secretion, alkaline phosphatase activity, but had no effects on in vitro mineralization capacity. In conclusion, lansoprazole acts as a direct covalent inhibitor of cysteine proteases via disulphide bonds with the SH group in the protease active site. Such inhibition of cysteine proteases could explain some of the off-target effects of PPIs.
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Affiliation(s)
- Tatjana Bosnjak
- Section for Pharmacology and Pharmaceutical Biosciences, School of Pharmacy, University of Oslo, Oslo, Norway
| | - Rigmor Solberg
- Section for Pharmacology and Pharmaceutical Biosciences, School of Pharmacy, University of Oslo, Oslo, Norway
| | - Paya Diana Hemati
- Section for Pharmacology and Pharmaceutical Biosciences, School of Pharmacy, University of Oslo, Oslo, Norway
| | - Abbas Jafari
- Department of Cellular and Molecular Medicine, Novo Nordisk Foundation Center for Stem Cell Biology (DanStem), University of Copenhagen, Copenhagen, Denmark
| | - Moustapha Kassem
- Department of Cellular and Molecular Medicine, Novo Nordisk Foundation Center for Stem Cell Biology (DanStem), University of Copenhagen, Copenhagen, Denmark.,Department of Endocrinology and Metabolism, Odense University Hospital & University of Southern Denmark, Odense, Denmark
| | - Harald Thidemann Johansen
- Section for Pharmacology and Pharmaceutical Biosciences, School of Pharmacy, University of Oslo, Oslo, Norway
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Massironi S, Cavalcoli F, Zilli A, Del Gobbo A, Ciafardini C, Bernasconi S, Felicetta I, Conte D, Peracchi M. Relevance of vitamin D deficiency in patients with chronic autoimmune atrophic gastritis: a prospective study. BMC Gastroenterol 2018; 18:172. [PMID: 30409113 PMCID: PMC6225568 DOI: 10.1186/s12876-018-0901-0] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/05/2018] [Accepted: 10/30/2018] [Indexed: 02/08/2023] Open
Abstract
Background Chronic autoimmune atrophic gastritis (CAAG) is an autoimmune disease characterized by hypo/achlorhydria. A role of CAAG in the pathogenesis of nutritional deficiencies has been reported, therefore we hypothesized a possible association between CAAG and 25-OH-Vitamin D [25(OH)D] deficiency. Aim of the present study is to evaluate the prevalence of 25(OH)D deficiency in CAAG patients. Methods: 87 CAAG patients (71 females; mean age 63.5 ± 12.8 years) followed at our Centre from January 2012 to July 2015 were consecutively evaluated. 25(OH)D, vitamin B12, parathormone, and calcium were measured in all the CAAG patients. The results were compared with a control group of 1232 healthy subjects. Results In the CAAG group the mean 25(OH)D levels were significantly lower than in the control group (18.8 vs. 27.0 ng/ml, p < 0.0001). 25(OH)D levels < 20 ng/ml was observed in 57 patients, while levels < 12.5 ng/ml in 27 patients. A significant correlation between vitamin B12 values at diagnosis and 25(OH)D levels was observed (rs = 0.25, p = 0.01). Interestingly, the CAAG patients with moderate/severe gastric atrophy had lower 25(OH)D values as compared to those with mild atrophy (11.8 vs. 20 ng/ml; p = 0.0047). Moreover, the 25(OH)D levels were significantly lower in CAAG patients with gastric carcinoid as compared to those without gastric carcinoid (11.8 vs. 19.8 ng/ml; p = 0,0041). Conclusion Data from the present study showed a significant reduction of 25(OH)D levels in CAAG patients and a possible impairment of vitamin D absorption in CAAG may be postulated. Any implication to the genesis of gastric carcinoids remains to be elucidated.
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Affiliation(s)
- Sara Massironi
- Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Federica Cavalcoli
- Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy. .,Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy.
| | - Alessandra Zilli
- Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.,Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy
| | - Alessandro Del Gobbo
- Division of Pathology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, 20122, Milan, Italy
| | - Clorinda Ciafardini
- Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Susanna Bernasconi
- Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Irene Felicetta
- Laboratory of Clinical Chemistry and Microbiology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Dario Conte
- Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Maddalena Peracchi
- Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
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Freedberg DE, Kim LS, Yang YX. The Risks and Benefits of Long-term Use of Proton Pump Inhibitors: Expert Review and Best Practice Advice From the American Gastroenterological Association. Gastroenterology 2017; 152:706-715. [PMID: 28257716 DOI: 10.1053/j.gastro.2017.01.031] [Citation(s) in RCA: 542] [Impact Index Per Article: 67.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS The purpose of this review is to evaluate the risks associated with long-term use of proton pump inhibitors (PPIs), focusing on long-term use of PPIs for three common indications: gastroesophageal reflux disease (GERD), Barrett's esophagus (BE), and non-steroidal anti-inflammatory drug (NSAID) bleeding prophylaxis. METHODS The recommendations outlined in this review are based on expert opinion and on relevant publications from PubMed, EMbase, and the Cochrane library (through July 2016). To identify relevant ongoing trials, we queried clinicaltrials.gov. To assess the quality of evidence, we used a modified approach based on the GRADE Working Group. The Clinical Practice Updates Committee of the American Gastroenterological Association has reviewed these recommendations. Best Practice Advice 1: Patients with GERD and acid-related complications (ie, erosive esophagitis or peptic stricture) should take a PPI for short-term healing, maintenance of healing, and long-term symptom control. Best Practice Advice 2: Patients with uncomplicated GERD who respond to short-term PPIs should subsequently attempt to stop or reduce them. Patients who cannot reduce PPIs should consider ambulatory esophageal pH/impedance monitoring before committing to lifelong PPIs to help distinguish GERD from a functional syndrome. The best candidates for this strategy may be patients with predominantly atypical symptoms or those who lack an obvious predisposition to GERD (eg, central obesity, large hiatal hernia). Best Practice Advice 3: Patients with Barrett's esophagus and symptomatic GERD should take a long-term PPI. Best Practice Advice 4: Asymptomatic patients with Barrett's esophagus should consider a long-term PPI. Best Practice Advice 5: Patients at high risk for ulcer-related bleeding from NSAIDs should take a PPI if they continue to take NSAIDs. Best Practice Advice 6: The dose of long-term PPIs should be periodically reevaluated so that the lowest effective PPI dose can be prescribed to manage the condition. Best Practice Advice 7: Long-term PPI users should not routinely use probiotics to prevent infection. Best Practice Advice 8: Long-term PPI users should not routinely raise their intake of calcium, vitamin B12, or magnesium beyond the Recommended Dietary Allowance (RDA). Best Practice Advice 9: Long-term PPI users should not routinely screen or monitor bone mineral density, serum creatinine, magnesium, or vitamin B12. Best Practice Advice 10: Specific PPI formulations should not be selected based on potential risks.
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Affiliation(s)
- Daniel E Freedberg
- Division of Digestive and Liver Diseases, Columbia University Medical Center, New York, New York.
| | - Lawrence S Kim
- South Denver Gastroenterology, P.C., Littleton, Colorado
| | - Yu-Xiao Yang
- Divison of Gastroenterology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
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Cavalcoli F, Zilli A, Conte D, Massironi S. Micronutrient deficiencies in patients with chronic atrophic autoimmune gastritis: A review. World J Gastroenterol 2017; 23:563-572. [PMID: 28216963 PMCID: PMC5292330 DOI: 10.3748/wjg.v23.i4.563] [Citation(s) in RCA: 65] [Impact Index Per Article: 8.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/27/2016] [Revised: 10/08/2016] [Accepted: 11/13/2016] [Indexed: 02/06/2023] Open
Abstract
Chronic atrophic autoimmune gastritis (CAAG) is an organ-specific autoimmune disease characterized by an immune response, which is directed towards the parietal cells and intrinsic factor of the gastric body and fundus and leads to hypochlorhydria, hypergastrinemia and inadequate production of the intrinsic factor. As a result, the stomach’s secretion of essential substances, such as hydrochloric acid and intrinsic factor, is reduced, leading to digestive impairments. The most common is vitamin B12 deficiency, which results in a megaloblastic anemia and iron malabsorption, leading to iron deficiency anemia. However, in the last years the deficiency of several other vitamins and micronutrients, such as vitamin C, vitamin D, folic acid and calcium, has been increasingly described in patients with CAAG. In addition the occurrence of multiple vitamin deficiencies may lead to severe hematological, neurological and skeletal manifestations in CAAG patients and highlights the importance of an integrated evaluation of these patients. Nevertheless, the nutritional deficiencies in CAAG are largely understudied. We have investigated the frequency and associated features of nutritional deficiencies in CAAG in order to focus on any deficit that may be clinically significant, but relatively easy to correct. This descriptive review updates and summarizes the literature on different nutrient deficiencies in CAAG in order to optimize the treatment and the follow-up of patients affected with CAAG.
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Tahir R, Patel PN. Role of Proton Pump Inhibitors in Calcium Absorption, Bone Resorption, and Risk of Hip Fracture. J Pharm Technol 2016. [DOI: 10.1177/875512250702300504] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
Abstract
Objective: To review the influence of proton pump inhibitors (PPIs) on calcium absorption, bone remodeling, and fracture risk. Data Sources: A search via MEDLINE (1966–April 2007) was performed using the search terms proton pump inhibitors, omeprazole, calcium absorption, calcium malabsorption, bone resorption, and fracture risk. Study Selection and Data Extraction: English-language literature, including abstracts, preclinical and clinical trials, and review articles, were identified from the data sources and reviewed. Data Synthesis: Data on the effect of PPIs on calcium absorption are conflicting; however, the majority of data indicate that PPIs decrease intestinal calcium absorption, which could negatively affect bone strength. In particular, calcium carbonate may be more difficult to absorb in an environment with elevated pH due to PPI use. Data on the role of PPIs in osteoclast function are also conflicting, with one human study indicating decreased bone resorption due to inhibition of osteoclast function and another human study indicating no association between PPIs and osteoclast function. The risk of fracture with PPI use was evaluated in 2 studies, and both studies found an increased risk of fracture of 14–44% after PPI use. Conclusions: PPI use may increase a patient's risk of fracture. Additional studies are needed before causality can be established.
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Affiliation(s)
- Rabia Tahir
- RABIA TAHIR PharmD, Assistant Clinical Professor; Internal Medicine Specialist, Department of Clinical Pharmacy Practice, College of Pharmacy and Allied Health Professions, St. John's University, Jamaica, NY
| | - Priti N Patel
- PRITI N PATEL PharmD BCPS, Assistant Clinical Professor; Director, Drug Information Center, Department of Clinical Pharmacy Practice, College of Pharmacy and Allied Health Professions, St. John's University
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Lin YS, Huang TT, Hsu YJ, Lin JYT, Wu CH, Hu YH. Refractory hypocalcemia and hypomagnesemia associated with the use of an oral proton-pump inhibitor in a patient with hypoparathyroidism. Tzu Chi Med J 2015. [DOI: 10.1016/j.tcmj.2014.05.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/25/2022] Open
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13
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The therapeutic effectiveness of the coadministration of weekly risedronate and proton pump inhibitor in osteoporosis treatment. J Osteoporos 2014; 2014:607145. [PMID: 25436170 PMCID: PMC4241743 DOI: 10.1155/2014/607145] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/28/2014] [Revised: 10/11/2014] [Accepted: 10/12/2014] [Indexed: 11/17/2022] Open
Abstract
This trial was conducted to investigate the long-term effects of proton pump inhibitor (PPI) coadministration on the efficacy of weekly risedronate treatment for osteoporosis. Ninety-six women over 50 years old with low bone mineral density (BMD) participated in this trial. Subjects were randomly divided into 2 groups: a 17.5 mg dose of sodium risedronate was administered weekly, with or without a daily 10 mg dose of sodium rabeprazole (n = 49 and 47 in the BP + PPI and BP groups, resp.). The following biomarkers were measured at the baseline and every 3 months: bone-specific alkaline phosphatase, N-terminal telopeptide of type I collagen corrected for creatinine, parathyroid hormone, BMD of the lumbar spine, and physical parameters evaluated according to the SF-36v2 Health Survey. Statistical comparisons of these parameters were performed after 6, 12, 18, and 24 months. The Δ values of improvement in physical functioning after 12 months and bodily pain after 6 and 12 months in the BP + PPI group were significantly larger than those in the BP group. These results suggest that PPI does not adversely affect bone metabolism. Alternatively, approved bone formation by concomitant PPI treatment may have had favorable effects on the improvement of bodily pain and physical functions.
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Keller J, Schinke T. The role of the gastrointestinal tract in calcium homeostasis and bone remodeling. Osteoporos Int 2013; 24:2737-48. [PMID: 23536255 DOI: 10.1007/s00198-013-2335-4] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/19/2012] [Accepted: 02/25/2013] [Indexed: 12/11/2022]
Abstract
While skeletal biology was approached in a rather isolated fashion in the past, an increasing understanding of the interplay between extraskeletal organs and bone remodeling has been obtained in recent years. This review will discuss recent advances in the field that have shed light on how the gastrointestinal tract and bone relate to each other. In particular, the importance of the GI tract in maintaining calcium homeostasis and skeletal integrity will be reviewed as impaired gastric acid production represents a major public health problem with possible implications for sufficient calcium absorption. Osteoporosis, the most prevalent bone disease worldwide, is caused not only by intrinsic defects affecting bone cell differentiation and function but also by a large set of extrinsic factors including hormonal disturbances, malnutrition, and iatrogenic drug application. Given the skeletal requirements of calcium, amino acids, and energy for bone turnover and renewal, it is not surprising that the gastrointestinal (GI) tract is of major importance for skeletal integrity.
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Affiliation(s)
- J Keller
- Department of Osteology and Biomechanics, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany
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Itoh S, Sekino Y, Shinomiya KI, Takeda S. The effects of risedronate administered in combination with a proton pump inhibitor for the treatment of osteoporosis. J Bone Miner Metab 2013; 31:206-11. [PMID: 23138352 DOI: 10.1007/s00774-012-0406-9] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/10/2012] [Accepted: 10/21/2012] [Indexed: 10/27/2022]
Abstract
This study was performed to investigate the effects of the co-administration of proton pump inhibitor (PPI) on the efficacy of bisphosphonate (BP) treatment for osteoporosis. A total of 180 women with low bone mineral density were randomly divided into four groups, one in which sodium risedronate was administered with sodium rabeprazole and one in which only risedronate was administered (BP + PPI and BP groups, respectively). The biomarkers were measured at the baseline and every 3 months, inlcuding: N-terminal telopeptide of type I collagen corrected for creatinine, bone-specific alkaline phosphatase (BAP), parathyroid hormone, bone mineral density (BMD) of the lumbar spine and physical parameters evaluated according to the SF-36v2™ Health Survey. Statistical comparisons of these parameters were performed after 9 months. Data were available for a total of 137 patients (62 in the BP group and 75 in the BP + PPI group). The Δ % value of increase in BMD and improvement of physical functioning in the BP + PPI group were significantly larger, and its decrease in BAP in the BP + PPI group was significantly smaller than that in the BP group. It is expected that risedronate administration in combination with a PPI may be more effective not only for treating osteoporosis but also improving physical fitness than treatment with risedronate alone.
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Affiliation(s)
- Soichiro Itoh
- Department of Orthopaedic Surgery, Kawakita General Hospital, 1-7-3 Asagaya-kita, Suginami-ku, Tokyo 166-8588, Japan.
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Kopic S, Geibel JP. Gastric acid, calcium absorption, and their impact on bone health. Physiol Rev 2013; 93:189-268. [PMID: 23303909 DOI: 10.1152/physrev.00015.2012] [Citation(s) in RCA: 110] [Impact Index Per Article: 9.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
Calcium balance is essential for a multitude of physiological processes, ranging from cell signaling to maintenance of bone health. Adequate intestinal absorption of calcium is a major factor for maintaining systemic calcium homeostasis. Recent observations indicate that a reduction of gastric acidity may impair effective calcium uptake through the intestine. This article reviews the physiology of gastric acid secretion, intestinal calcium absorption, and their respective neuroendocrine regulation and explores the physiological basis of a potential link between these individual systems.
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Affiliation(s)
- Sascha Kopic
- Department of Surgery and Cellular and Molecular Physiology, Yale School of Medicine, New Haven, Connecticut, USA
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Abstract
Proton pump inhibitors (PPIs) have been widely used since their introduction in the late 1980s because they are highly effective for acid-related conditions. However, some recent epidemiological studies have suggested a positive association between PPI therapy and the risk of osteoporotic fractures. The potential mechanisms underlying this association may be related to the physiologic effects of chronic acid suppression on calcium metabolism. First, chronic hypergastrinemia induced by PPI therapy may lead to parathyroid hyperplasia, resulting in increased loss of calcium from the bone. Second, profound gastric acid suppression may reduce the bioavailability of calcium for intestinal absorption. I will review the published evidence regarding these potential links and discuss their clinical implications.
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Affiliation(s)
- Yu-Xiao Yang
- Division of Gastroenterology, The Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104-6021, USA.
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Durand C, Willett KC, Desilets AR. Proton Pump Inhibitor use in Hospitalized Patients: Is Overutilization Becoming a Problem? CLINICAL MEDICINE INSIGHTS. GASTROENTEROLOGY 2012; 5:65-76. [PMID: 24833936 PMCID: PMC3987764 DOI: 10.4137/cgast.s9588] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
Proton pump inhibitors (PPIs) are among the most common classes of medications prescribed. Though they were previously thought of as safe, recent literature has shown risks associated with their use including increased risk for Clostridium difficile infection, pneumonia, and fractures. Due to these risks, it is important to determine if PPIs are being used appropriately. This review evaluates seven studies in hospitalized patients. Additionally, this review evaluates literature pertaining to recently discovered adverse reactions; all studies found PPIs are being overutilized. Findings highlight the importance of evaluating appropriate therapy with these agents and recommending discontinuation if a proper indication does not exist.
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Affiliation(s)
- Cheryl Durand
- Massachusetts College of Pharmacy and Health Sciences, Manchester, NH
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CERVELLI MATTHEWJ, SHAMAN AHMED, MEADE ANTHONY, CARROLL ROBERT, MCDONALD STEPHENP. Effect of gastric acid suppression with pantoprazole on the efficacy of calcium carbonate as a phosphate binder in haemodialysis patients. Nephrology (Carlton) 2012; 17:458-65. [DOI: 10.1111/j.1440-1797.2012.01604.x] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/01/2022]
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Desilets AR, Asal NJ, Dunican KC. Considerations for the use of proton-pump inhibitors in older adults. ACTA ACUST UNITED AC 2012; 27:114-20. [PMID: 22330952 DOI: 10.4140/tcp.n.2012.114] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023]
Abstract
OBJECTIVE To investigate current concerns regarding the use of proton-pump inhibitors (PPIs) in older adults. DATA SOURCES A literature search was conducted in MEDLINE (1948 to April week 3 2011) to identify relevant publications. Key words searched included proton-pump inhibitor, safety, adverse events, elderly, and older adults. Additional data sources were obtained through a bibliographic review of selected articles. DATA SELECTION Relevant studies conducted in older adults published in English that examined risks associated with the use of PPIs were included in this review. DATA SYNTHESIS The older adult population in the United States is growing at an astounding rate. With the increase in age, there are many factors that make the elderly susceptible to acid-related gastrointestinal disorders that require treatment with PPIs. However, PPI use in the elderly has been shown to lead to a number of health concerns. Recent data have shown that PPI use is associated with an increased risk of fractures, Clostridium difficile infection, community-acquired pneumonia, vitamin and mineral deficiencies, and drug interactions. These concerns will be further investigated and weighed against the benefits of PPI use in this population. CONCLUSIONS Patient-specific characteristics must be taken into consideration when recommending and/or prescribing PPIs to older adults.
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Affiliation(s)
- Alicia R Desilets
- Massachusetts College of Pharmacy and Health Sciences, Manchester, NH, USA.
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Abstract
There have been recent concerns about the safety of proton pump inhibitors (PPIs). We focus here on 3 specific concerns-the possible interaction between PPIs and clopidogrel, the postulated link between PPI use and fractures, and the possibility that long-term PPI use might lead to hypomagnesemia. There is evidence for an in vitro interaction between clopidogrel and at least some PPIs. The Food and Drug Administration (FDA) has warned against the use of certain PPIs by patients on clopidogrel. However, a randomized controlled trial that compared clopidogrel alone with the combination of clopidogrel and omeprazole found no increase in adverse cardiovascular outcomes and a reduction in the rate of adverse gastrointestinal outcomes attributable to omeprazole. PPI use may be a weak risk factor for certain fractures, but the quality of evidence is relatively poor and there is a strong possibility of confounding. The mechanism whereby PPI use might increase fracture risk is unknown. Currently, no additional measures concerning calcium supplementation or bone mineral density monitoring are recommended for patients on a PPI. The FDA has suggested monitoring serum magnesium levels in patients on PPI therapy. The mechanism and frequency of PPI-induced hypomagnesemia are unclear. PPI treatment should not be withheld from patients who genuinely require it, but the PPI should be taken in the lowest effective dose and only for as long as clinically indicated. The same is, of course, true for all medicines. The benefits of PPI therapy greatly outweigh the risks.
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Mechanism of drug interaction between a Kampo medicine, byakkokaninjinto, and tetracycline in rats. J Infect Chemother 2012; 18:75-82. [DOI: 10.1007/s10156-011-0294-2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2011] [Accepted: 08/09/2011] [Indexed: 11/26/2022]
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Fohl AL, Regal RE. Proton pump inhibitor-associated pneumonia: Not a breath of fresh air after all? World J Gastrointest Pharmacol Ther 2011; 2:17-26. [PMID: 21731913 PMCID: PMC3124633 DOI: 10.4292/wjgpt.v2.i3.17] [Citation(s) in RCA: 57] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/15/2011] [Revised: 05/25/2011] [Accepted: 06/02/2011] [Indexed: 02/06/2023] Open
Abstract
Over the past two decades, proton pump inhibitors (PPIs) have emerged as highly effective and relatively safe agents for the treatment of a variety of gastrointestinal disorders. Unfortunately, this desirable pharmacological profile has also contributed to superfluous and widespread use in both the inpatient and outpatient settings. While generally well-tolerated, research published over the last decade has associated these agents with increased risks of Clostridium difficile disease, fractures likely due to calcium malabsorption and both community-acquired (CAP) and hospital-acquired pneumonias (HAP). The mechanism behind PPI-associated pneumonia may be multifactorial, but is thought to stem from compromising the stomach’s “acid mantle” against gastric colonization of acid-labile pathogenic bacteria which then may be aspirated. A secondary postulate is that PPIs, through their inhibition of extra-gastric H+/K+-ATPase enzymes, may reduce the acidity of the upper aerodigestive tract, thus resulting in increased bacterial colonization of the larynx, esophagus and lungs. To date, several retrospective case control studies have been published looking at the association between PPI use and CAP. Some studies found a temporal relationship between PPI exposure and the incidence of pneumonia, but only two could define a dose-response relationship. Furthermore, other studies found an inverse correlation between duration of PPI use and risk of CAP. In terms of HAP, we reviewed two retrospective cohort studies and one prospective study. One retrospective study in a medical ICU found no increased association of HAP in PPI-exposed patients compared to no acid-lowering therapy, while the other in cardiothoracic surgery patients showed a markedly increased risk compared to those receiving H2RAs. The one prospective study in ICU patients showed an increased risk of HAP with PPIs, but not with H2RAs. In conclusion, the current literature shows a slight trend toward an association between PPI use and pneumonia and an increased risk with PPIs over H2RAs, but the findings are not consistent across all studies. Larger controlled trials still need to be done to better identify the risk that PPIs impart towards patients contracting CAP or HAP. Until these are completed, we will have to continue to extrapolate across smaller controlled trials to predict the associated risks in our respective patient populations. In the interim, it appears prudent to limit the use of PPIs to situations where they are clinically indicated and, in such cases, use them at the lowest effective dose. In the case of prescribing for stress ulcer prophylaxis in ICU patients, perhaps H2RAs should be used as the preferred agents over PPIs.
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Affiliation(s)
- Alexander L Fohl
- Alexander L Fohl, University of Michigan Hospitals and College of Pharmacy, Ann Arbor, MI 48109-5008,, United States
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Quesada Gómez JM, Blanch Rubió J, Díaz Curiel M, Díez Pérez A. Calcium citrate and vitamin D in the treatment of osteoporosis. Clin Drug Investig 2011; 31:285-98. [PMID: 21405146 DOI: 10.1007/bf03256927] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
The combination of calcium with vitamin D (vitamin D(3) [colecalciferol]) forms the basis of preventive and therapeutic regimens for osteoporosis. A number of studies have suggested that the combination of calcium and vitamin D is effective when administered at respective dosages of at least 1200 mg and 800 IU per day, although efficacy is, as expected, affected by patient compliance. Overall, treatment with this combination appears to be effective in reducing the incidence of non-vertebral and hip fractures. Also, in all drug studies (of antiresorptive and anabolic agents and strontium ranelate) that demonstrated a reduction in risk of osteoporotic fractures, patients also took calcium and vitamin D supplements. An important finding in this regard is that vitamin D levels have been demonstrated to be inadequate in more than half of women treated for osteoporosis in the US and Europe. The capacity of the small intestine to absorb calcium salts depends on the solubility and ionization of the salts. These properties vary for different salts, with fasting calcium citrate absorption being greater than that of calcium lactogluconate and calcium carbonate. Calcium citrate formulations taken between meals may help to prevent abdominal distension and flatulence, as well as minimize the risk of renal calculus formation, thus helping to optimize patient compliance. Therefore, calcium citrate combined with vitamin D is the combination of choice for the prevention or treatment of osteoporosis.
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Eom CS, Park SM, Myung SK, Yun JM, Ahn JS. Use of acid-suppressive drugs and risk of fracture: a meta-analysis of observational studies. Ann Fam Med 2011; 9:257-67. [PMID: 21555754 PMCID: PMC3090435 DOI: 10.1370/afm.1243] [Citation(s) in RCA: 84] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
PURPOSE Previous studies have reported inconsistent findings regarding the association between the use of acid-suppressive drugs such as proton pump inhibitors (PPIs) and histamine 2 receptor antagonists (H(2)RAs) and fracture risk. We investigated this association using meta-analysis. METHODS We searched MEDLINE (PubMed), EMBASE, and the Cochrane Library from inception through December 2010 using common key words. We included case-control, nested case-control, and cohort studies. Two evaluators independently reviewed and selected articles. We determined pooled effect estimates by using random-effects meta-analysis, because of heterogeneity. RESULTS Of 1,809 articles meeting our initial inclusion criteria, 5 case-control studies, 3 nested case-control studies, and 3 cohort studies were included in the final analyses. The pooled odds ratio (OR) for fracture was 1.29 (95% confidence interval [CI], 1.18-1.41) with use of PPIs and 1.10 (95% CI, 0.99-1.23) with use of H(2)RAs when compared with nonuse of the respective medications. Long-term use of PPIs increased the risk of any fracture (adjusted OR = 1.30; 95% CI, 1.15-1.48) and hip fracture risk (adjusted OR = 1.34; 95% CI, 1.09-1.66), whereas long-term H(2)RA use was not significantly associated with fracture risk. CONCLUSIONS We found possible evidence linking PPI use to an increased risk of fracture, but no association between H(2)RA use and fracture risk. Widespread use of PPIs with the potential risk of fracture is of great importance to public health. Clinicians should carefully consider their decision to prescribe PPIs for patients already having an elevated risk of fracture because of age or other factors.
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Affiliation(s)
- Chun-Sick Eom
- Department of Family Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea
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Sheen E, Triadafilopoulos G. Adverse effects of long-term proton pump inhibitor therapy. Dig Dis Sci 2011; 56:931-50. [PMID: 21365243 DOI: 10.1007/s10620-010-1560-3] [Citation(s) in RCA: 196] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/01/2010] [Accepted: 12/31/2010] [Indexed: 12/12/2022]
Abstract
Proton pump inhibitors have an excellent safety profile and have become one of the most commonly prescribed class of drugs in primary and specialty care. Long-term, sometimes lifetime, use is becoming increasingly common, often without appropriate indications. This paper is a detailed review of the current evidence on this important topic, focusing on the potential adverse effects of long-term proton pump inhibitor use that have generated the greatest concern: B12 deficiency; iron deficiency; hypomagnesemia; increased susceptibility to pneumonia, enteric infections, and fractures; hypergastrinemia and cancer; drug interactions; and birth defects. We explain the pathophysiological mechanisms that may underlie each of these relationships, review the existing evidence, and discuss implications for clinical management. The benefits of proton pump inhibitor use outweigh its risks in most patients. Elderly, malnourished, immune-compromised, chronically ill, and osteoporotic patients theoretically could be at increased risk from long-term therapy.
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Affiliation(s)
- Edward Sheen
- Department of Medicine and Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA 94305, USA.
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Pouwels S, Lalmohamed A, Souverein P, Cooper C, Veldt BJ, Leufkens HG, de Boer A, van Staa T, de Vries F. Use of proton pump inhibitors and risk of hip/femur fracture: a population-based case-control study. Osteoporos Int 2011; 22:903-10. [PMID: 20585937 PMCID: PMC3034906 DOI: 10.1007/s00198-010-1337-8] [Citation(s) in RCA: 61] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/24/2010] [Accepted: 05/31/2010] [Indexed: 12/19/2022]
Abstract
UNLABELLED Previous studies evaluated the association between proton pump inhibitor (PPI) use and subsequent fracture risk, but they showed ambiguous results. Therefore, the objective was to evaluate this association in a different study population. Our findings show that there is probably no causal relationship between PPI use and hip fracture risk. INTRODUCTION Previous studies evaluated the association between PPI use and subsequent fracture risk, but they showed ambiguous results. To further test these conflicting results, the objective of this study was to evaluate the association between the use of PPIs and the risk of hip/femur fracture in a different study population. METHODS A case-control study was conducted using data from the Dutch PHARMO record linkage system. The study population included 6,763 cases aged 18 years and older with a first hip/femur fracture during enrollment and 26,341 age-, gender- and region-matched controls. RESULTS Current users of PPIs had an increased risk of hip/femur fracture yielding an adjusted odds ratio (AOR) of 1.20 (95% CI 1.04-1.40). Fracture risk attenuated with increasing durations of use, resulting in AORs of 1.26 (95% CI 0.94-1.68) in the first 3 months, 1.31 (95% CI 0.97-1.75) between 3 and 12 months, 1.18 (95% CI 0.92-1.52) between 13 and 36 months and 1.09 (95% CI 0.81-1.47) for use longer than 36 months. CONCLUSION Our findings show that there is probably no causal relationship between PPI use and hip fracture risk. The observed association may be the result of unmeasured distortions: although current use of PPIs was associated with a 1.2-fold increased risk of hip/femur fracture, the positive association was attenuated with longer durations of continuous use. Our findings do not support that discontinuation of PPIs decreases risk of hip fracture in elderly patients.
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Affiliation(s)
- S. Pouwels
- Division of Pharmacoepidemiology and Pharmacotherapy, Utrecht Institute for Pharmaceutical Sciences, Universiteit Utrecht, P.O. Box 80082, 3508 TB Utrecht, The Netherlands
| | - A. Lalmohamed
- Division of Pharmacoepidemiology and Pharmacotherapy, Utrecht Institute for Pharmaceutical Sciences, Universiteit Utrecht, P.O. Box 80082, 3508 TB Utrecht, The Netherlands
| | - P. Souverein
- Division of Pharmacoepidemiology and Pharmacotherapy, Utrecht Institute for Pharmaceutical Sciences, Universiteit Utrecht, P.O. Box 80082, 3508 TB Utrecht, The Netherlands
| | - C. Cooper
- MRC Epidemiology Resource Centre, University of Southampton, Southampton General Hospital, Southampton, UK
- Institute of Musculoskeletal Sciences, University of Oxford, Oxford, UK
| | - B. J. Veldt
- Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center, Rotterdam, Netherlands
| | - H. G. Leufkens
- Division of Pharmacoepidemiology and Pharmacotherapy, Utrecht Institute for Pharmaceutical Sciences, Universiteit Utrecht, P.O. Box 80082, 3508 TB Utrecht, The Netherlands
| | - A. de Boer
- Division of Pharmacoepidemiology and Pharmacotherapy, Utrecht Institute for Pharmaceutical Sciences, Universiteit Utrecht, P.O. Box 80082, 3508 TB Utrecht, The Netherlands
| | - T. van Staa
- Division of Pharmacoepidemiology and Pharmacotherapy, Utrecht Institute for Pharmaceutical Sciences, Universiteit Utrecht, P.O. Box 80082, 3508 TB Utrecht, The Netherlands
- MRC Epidemiology Resource Centre, University of Southampton, Southampton General Hospital, Southampton, UK
- General Practice Research Database, Medicines and Healthcare Products Regulatory Agency, London, UK
| | - F. de Vries
- Division of Pharmacoepidemiology and Pharmacotherapy, Utrecht Institute for Pharmaceutical Sciences, Universiteit Utrecht, P.O. Box 80082, 3508 TB Utrecht, The Netherlands
- MRC Epidemiology Resource Centre, University of Southampton, Southampton General Hospital, Southampton, UK
- General Practice Research Database, Medicines and Healthcare Products Regulatory Agency, London, UK
- Present Address: Utrecht Institute for Pharmaceutical Sciences, Universiteit Utrecht, Sorbonnelaan 16, 3584 CA Utrecht, The Netherlands
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Quesada Gómez JM, Rubió JB, Curiel MD, Pérez AD. Calcium Citrate and Vitamin D in the Treatment of Osteoporosis. Clin Drug Investig 2011. [DOI: 10.2165/11584940-000000000-00000] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/02/2022]
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Chiu HF, Huang YW, Chang CC, Yang CY. Use of proton pump inhibitors increased the risk of hip fracture: a population-based case-control study. Pharmacoepidemiol Drug Saf 2011; 19:1131-6. [PMID: 20872906 DOI: 10.1002/pds.2026] [Citation(s) in RCA: 43] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
PURPOSE To investigate whether the use of proton pump inhibitor (PPIs) was associated with an increased risk of hip fracture. METHODS We conducted a population-based case-control study in Taiwan. Data were retrospectively collected from the Taiwan National health Insurance Research Database. Cases included all patients with a newly diagnosed of hip fracture in 2005 and 2006 (n = 1241). The controls were pair matched to cases by age, sex, and index date. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by using multiple logistic regression. RESULTS Having been prescribed more than 28 defined daily dose (DDDs) of PPIs was associated with an increased risk for hip fracture in multivariate analyses (adjustments for matching variables and medication use) (at 29-70 DDDs, OR = 1.67, 95% CI = 1.11-2.51 and at >70 DDDs, OR = 2.51, 95% CI = 1.77-3.55). There was a significant trend toward increasing hip fracture risk with increasing cumulative DDDs of PPIs (p for trend <0.0001). CONCLUSIONS This study provides evidence that PPIs use is associated with an increased risk of hip fracture in a dose-response manner.
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Affiliation(s)
- Hui-Fen Chiu
- Institute of Pharmacology, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
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Milk Alkali and Hydrochlorothiazide: A Case Report. Case Rep Med 2011; 2011:729862. [PMID: 21738535 PMCID: PMC3114559 DOI: 10.1155/2011/729862] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2010] [Revised: 02/12/2011] [Accepted: 03/28/2011] [Indexed: 11/26/2022] Open
Abstract
Hypercalcemia is a relatively common clinical problem in both outpatient and inpatient settings. Primary pathophysiology is the entry of calcium that exceeds its excretion into urine or deposition in bone into circulation. Among a wide array of causes of hypercalcemia, hyperparathyroidism and malignancy are the most common, accounting for greater than 90 percent of cases. Concordantly, there has been a resurgence of milk-alkali syndrome associated with the ingestion of large amounts of calcium and absorbable alkali, making it the third leading cause of hypercalcemia (Beall and Scofield, 1995 and Picolos et al., 2005). This paper centers on a case of over-the-counter calcium and alkali ingestion for acid reflux leading to milk alkali with concordant use of thiazide diuretic for hypertension.
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Yang YX, Metz DC. Safety of proton pump inhibitor exposure. Gastroenterology 2010; 139:1115-27. [PMID: 20727892 DOI: 10.1053/j.gastro.2010.08.023] [Citation(s) in RCA: 156] [Impact Index Per Article: 10.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/15/2010] [Revised: 08/16/2010] [Accepted: 08/16/2010] [Indexed: 12/12/2022]
Abstract
Proton pump (H(+)/K(+)-adenosine triphosphatase) inhibitors (PPIs) are widely used to treat patients with acid-related disorders because they are generally perceived to be safe and effective. However, as with any pharmacologic agent, they have the potential for side effects. Many studies have examined the side effects of long-term or short-term PPI exposure. We review the mechanism of action of PPIs, focusing on recently released products that might have greater risks of adverse effects than older products because of increased potency and/or duration of action. We summarize the data available on the putative adverse effects of PPI therapy and propose guidelines for clinicians who prescribe these agents to limit the potential for adverse outcomes in users of these effective therapeutic agents.
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Affiliation(s)
- Yu-Xiao Yang
- Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA.
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Sipponen P, Härkönen M. Hypochlorhydric stomach: a risk condition for calcium malabsorption and osteoporosis? Scand J Gastroenterol 2010; 45:133-8. [PMID: 19958055 DOI: 10.3109/00365520903434117] [Citation(s) in RCA: 69] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
Malabsorption of dietary calcium is a cause of osteoporosis. Dissolution of calcium salts (e.g. calcium carbonate) in the stomach is one step in the proper active and passive absorption of calcium as a calcium ion (Ca(2+)) in the proximal small intestine. Stomach acid markedly increases dissolution and ionization of poorly soluble calcium salts. If acid is not properly secreted, calcium salts are minimally dissolved (ionized) and, subsequently, may not be properly and effectively absorbed. Atrophic gastritis, gastric surgery, and high-dose, long-term use of antisecretory drugs markedly reduce acid secretion and may, therefore, be risk conditions for malabsorption of dietary and supplementary calcium, and may thereby increase the risk of osteoporosis in the long term.
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Fournier MR, Targownik LE, Leslie WD. Proton pump inhibitors, osteoporosis, and osteoporosis-related fractures. Maturitas 2009; 64:9-13. [PMID: 19674854 DOI: 10.1016/j.maturitas.2009.07.006] [Citation(s) in RCA: 28] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2009] [Revised: 07/11/2009] [Accepted: 07/14/2009] [Indexed: 12/14/2022]
Abstract
Proton pump inhibitors (PPIs) are among the most commonly prescribed medications today with an excellent short-term safety profile. Recently, a number of studies from a variety of data sources have reported an association between PPI use and hip fractures. However, there is not yet any direct evidence of a causal link between PPI use and the development of hip fracture. In the following paper, we will review the recent studies which have described this association between PPI use and hip fracture, and discuss the evidence supporting the likelihood of this association being causal, using data from previous work on the effects of surgical and pharmacological inhibition of gastric acid secretion on calcium absorption and bone mineral density. We will conclude by summarizing the current state of evidence on the relationship between gastric acid inhibition and the risk of fracture, and suggest management strategies for patients who require the long-term use of gastric acid inhibiting medications who also may be at risk for metabolic bone disease and fracture.
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Affiliation(s)
- Marc R Fournier
- Department of Internal Medicine, Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada.
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Targownik LE, Lix LM, Metge CJ, Prior HJ, Leung S, Leslie WD. Use of proton pump inhibitors and risk of osteoporosis-related fractures. CMAJ 2008; 179:319-26. [PMID: 18695179 DOI: 10.1503/cmaj.071330] [Citation(s) in RCA: 281] [Impact Index Per Article: 16.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022] Open
Abstract
BACKGROUND The use of proton pump inhibitors has been associated with an increased risk of hip fracture. We sought to further explore the relation between duration of exposure to proton pump inhibitors and osteoporosis-related fractures. METHODS We used administrative claims data to identify patients with a fracture of the hip, vertebra or wrist between April 1996 and March 2004. Cases were each matched with 3 controls based on age, sex and comorbidities. We calculated adjusted odds ratios (OR) for the risk of hip fracture and all osteoporosis-related fractures for durations of proton pump inhibitor exposure ranging from 1 or more years to more than 7 years. RESULTS We matched 15 792 cases of osteoporosis-related fractures with 47 289 controls. We did not detect a significant association between the overall risk of an osteoportic fracture and the use of proton pump inhibitors for durations of 6 years or less. However, exposure of 7 or more years was associated with increased risk of an osteoporosis-related fracture (adjusted OR 1.92, 95% confidence interval [CI] 1.16-3.18, p = 0.011). We also found an increased risk of hip fracture after 5 or more years of exposure (adjusted OR 1.62, 95% CI 1.02-2.58, p = 0.04), with even higher risk after 7 or more years exposure (adjusted OR 4.55, 95% CI 1.68-12.29, p = 0.002). INTERPRETATION Use of proton pump inhibitors for 7 or more years is associated with a significantly increased risk of an osteoporosis-related fracture. There is an increased risk of hip fracture after 5 or more years exposure. Further study is required to determine the clinical importance of this finding and to determine the value of osteoprotective medications for patients with long-term use of proton pump inhibitors.
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Affiliation(s)
- Laura E Targownik
- Department of Gastroenterology, Division of Internal Medicine, University of Manitoba, Winnipeg, Man
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Kakehasi AM, Mendes CMC, Coelho LGV, Castro LP, Barbosa AJA. The presence of Helicobacter Pylori in postmenopausal women is not a factor to the decrease of bone mineral density. ARQUIVOS DE GASTROENTEROLOGIA 2007; 44:266-70. [DOI: 10.1590/s0004-28032007000300016] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/20/2006] [Accepted: 05/10/2007] [Indexed: 11/22/2022]
Abstract
BACKGROUND: Osteoporosis affects approximately 30% of postmenopausal women. Gastrectomy, pernicious anemia, and more recently Helicobacter pylori infection, have all been implicated in the pathogenesis of osteoporosis. A reduced parietal cell mass is a common feature in these conditions. AIM: To study a possible relationship between chronic gastritis, parietal cell density of the oxyntic mucosa and bone mineral density in postmenopausal women, as chronic gastritis, Helicobacter pylori infection and osteoporosis are frequently observed in the elderly. METHODS: Fifty postmenopausal women (61.7 ± 7 years) were submitted to gastroduodenal endoscopy and bone densitometry by dual energy X-ray absorptiometry. Glandular atrophy was evaluated objectively by the determination of parietal cell density. Helicobacter pylori infection was evaluated by histology, urease test and breath test with 13C. RESULTS: Thirty-two patients (64%) presented chronic multifocal gastritis, and 20 of them (40%) showed signs of gastric mucosa atrophy. Lumbar spine osteoporosis was found in 18 patients (36%). The parietal cell density in patients with and without osteoporosis was 948 ± 188 and 804 ± 203 cells/mm², respectively. Ten osteoporotic patients (55%) and 24 non-osteoporotic patients (75%) were infected by Helicobacter pylori. CONCLUSION: Postmenopausal women with osteoporosis presented a well-preserved parietal cell density in comparison with their counterparts without osteoporosis. Helicobacter pylori infection was not different between the two groups. We concluded that neither atrophic chronic gastritis nor Helicobacter pylori seem to be a reliable risk factor to osteoporosis in postmenopausal women.
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Affiliation(s)
| | | | | | - Luiz P. Castro
- Federal University of Minas Gerais School of Medicine, Brazil
| | - Alfredo J. A. Barbosa
- Federal University of Minas Gerais School of Medicine; Federal University of Minas Gerais School of Medicine, Brazil
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Buzinaro EF, Almeida RNAD, Mazeto GMFS. Biodisponibilidade do cálcio dietético. ACTA ACUST UNITED AC 2006; 50:852-61. [PMID: 17160208 DOI: 10.1590/s0004-27302006000500005] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2004] [Accepted: 05/17/2006] [Indexed: 11/22/2022]
Abstract
O cálcio (Ca) dietético é fundamental para a saúde óssea. Tanto o teor como a biodisponibilidade do elemento nos alimentos devem ser considerados. Este artigo objetiva sumarizar os fatores envolvidos na absorção e destacar os alimentos com melhor disponibilidade do Ca. Este é absorvido principalmente no jejuno e o pH baixo parece favorecer sua absorção, que é maior no crescimento, na gestação/lactação e na carência de Ca ou fósforo (P), e menor no envelhecimento. As maiores fontes, e com melhor absorção, são os laticínios bovinos. Outros alimentos apresentam concentrações elevadas de Ca, mas com biodisponibilidade variável: os ricos em ácidos oxálico e fítico apresentariam uma menor absorção, enquanto que os ricos em carboidratos teriam uma absorção maior. Por apresentarem uma biodisponibilidade do Ca mais próxima da do leite bovino, o leite de outros animais, o de soja enriquecido e alguns vegetais, em quantidades adequadas, poderiam ser usados como alternativas a este.
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Affiliation(s)
- Elizabeth F Buzinaro
- Hospital das Clínicas, Departamento de Clínica Médica, Faculdade de Medicina de Botucatu, Universidade Estadual Paulista, Botucatu, SP
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Drinka PJ, Moore J, Boushon MC. Severe hypercalcemia after transition from calcium carbonate to calcium citrate in an elderly woman treated with ergocalciferol 50,000 IU per day. ACTA ACUST UNITED AC 2006; 4:70-4. [PMID: 16730623 DOI: 10.1016/j.amjopharm.2006.03.005] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/10/2006] [Indexed: 11/30/2022]
Abstract
BACKGROUND Absorption of calcium carbonate in the fasting state has been reported to be significantly compromised in subjects with achlorhydria. Although calcium carbonate malabsorption in the fasting state cannot be predicted, it might be corrected if the compound is administered with meals. However, administering calcium carbonate with meals is logistically challenging in long-term care facilities. OBJECTIVE The aim of this study was to report the case of a woman who was transitioned to calcium citrate and subsequently experienced symptomatic severe hypercalcemia. METHODS An 89-year-old female resident of the Wisconsin Veterans Home, a skilled nursing facility in King, Wisconsin, was receiving long-term treatment with ergocalciferol (vitamin D2) 50,000 IU/d. The patient also was receiving calcium carbonate supplements in the morning, and she rarely ate breakfast (fasting state). The patient was transitioned from 2000 mg/d of elemental calcium as carbonate to 1230 mg/d as citrate. RESULTS After being switched from calcium carbonate to calcium citrate, the patient developed severe symptomatic hypercalcemia (16.8 mg/dL), the primary cause of which was the administration of an inappropriately high dose of vitamin D. CONCLUSIONS We report a case of symptomatic severe hypercalcemia in a skilled nursing facility resident treated with an inappropriately high daily dose of vitamin D. Hypercalcemia manifested when calcium carbonate was replaced with calcium citrate.
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Beall DP, Henslee HB, Webb HR, Scofield RH. Milk-Alkali Syndrome: A Historical Review and Description of the Modern Version of the Syndrome. Am J Med Sci 2006; 331:233-42. [PMID: 16702792 DOI: 10.1097/00000441-200605000-00001] [Citation(s) in RCA: 58] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
Formerly recognized primarily for its historic interest as a disorder found in those taking milk and bicarbonate for peptide ulcer disease, milk-alkali syndrome (MAS) is experiencing a resurgence in its incidence largely due to the increased usage of calcium carbonate. The modern version of MAS affects a different patient population and has a different etiologic basis than was characterized in the original descriptions of the syndrome. Advances in parathyroid hormone measurement have allowed for improved diagnostic separation between MAS and hyperparathyroidism and have further explained some of the physiologic responses in the resolution of hypercalcemia. We have reviewed the reasons for the increasing incidence of MAS, described the typical patient with the modern form of the syndrome, and further elaborated on the pathophysiology of MAS, as it is currently understood. MAS is an important diagnostic consideration in the patient with hypercalcemia because the syndrome is now common and prompt diagnosis limits permanent kidney function impairment but depends strongly on considering the diagnosis as well as obtaining an over-the-counter medication history.
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Affiliation(s)
- Douglas P Beall
- Department of Medicine and Radiological Sciences, University of Oklahoma Health Science Center, Oklahoma City, Oklahoma 73104, USA
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40
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Picolos MK, Orlander PR. Calcium Carbonate Toxicity: The Updated Milk-Alkali Syndrome; Report of 3 Cases and Review of the Literature. Endocr Pract 2005; 11:272-80. [PMID: 16006300 DOI: 10.4158/ep.11.4.272] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
OBJECTIVE To describe 3 patients with calcium carbonate-induced hypercalcemia and gain insights into the cause and management of the milk-alkali syndrome. METHODS We report the clinical and laboratory data in 3 patients who presented with severe hypercalcemia (corrected serum calcium > or = 14 mg/dL) and review the pertinent literature on milk-alkali syndrome. RESULTS The 3 patients had acute renal insufficiency, relative metabolic alkalosis, and low parathyroid hormone (PTH), PTH-related peptide, and 1,25-dihydroxyvitamin D concentrations. No malignant lesion was found. Treatment included aggressive hydration and varied amounts of furosemide. The 2 patients with the higher serum calcium concentrations received pamidronate intravenously (60 and 30 mg, respectively), which caused severe hypocalcemia. Of the 3 patients, 2 were ingesting acceptable doses of elemental calcium (1 g and 2 g daily, respectively) in the form of calcium carbonate. In addition to our highlighted cases, we review the history, classification, pathophysiologic features, and treatment of milk-alkali syndrome and summarize the cases reported from early 1995 to November 2003. CONCLUSION Milk-alkali syndrome may be a common cause of unexplained hypercalcemia and can be precipitated by small amounts of orally ingested calcium carbonate in susceptible persons. Treatment with hydration, furosemide, and discontinuation of the calcium and vitamin D source is adequate. Pamidronate treatment is associated with considerable risk for hypocalcemia, even in cases of initially severe hypercalcemia.
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Affiliation(s)
- Michalis K Picolos
- Division of Endocrinology, Diabetes and Metabolism, The University of Texas-Houston Medical School, Houston, Texas 77030, USA
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Waisberg M, Black WD, Waisberg CM, Hale B. The effect of pH, time and dietary source of cadmium on the bioaccessibility and adsorption of cadmium to/from lettuce (Lactuca sativa L. cv. Ostinata). Food Chem Toxicol 2004; 42:835-42. [PMID: 15046830 DOI: 10.1016/j.fct.2004.01.007] [Citation(s) in RCA: 42] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2003] [Accepted: 01/21/2004] [Indexed: 11/22/2022]
Abstract
This study evaluated the influence of three variables in the effectiveness of an in vitro digestion protocol used to determine bioaccessibility of cadmium from the diet. The percentage of solubilized metal was measured in relation to digestion time, pH of each digestion phase and the dietary source of the metal in the diet. Because it would be convenient to add the metal to the diet before digestion instead of growing contaminated vegetables, the importance of metal incorporation in the plant in comparison to amendment through foliar spraying was also studied. From our results we conclude that the dietary source of metal in the protocols tested doesn't seem to be a significant factor when comparing the lettuce sprayed with cadmium with the lettuce that had cadmium incorporated in it, although the difference was barely significant (P=0.057). Time affects the digestion in different ways depending on the dietary source of cadmium. pH is a relevant factor in both intestinal and gastric phases and should be taken into consideration when analyzing the results from in vitro digestions. Since the intestinal phase in our experiments decreased the amount of cadmium solubilized during the digestion, we investigated the effect of pH on the adsorption of this metal to lettuce and found that there is an increased binding of cadmium at pH values above 3. Therefore we suggest that part of the reduction in bioaccessibility following intestinal digestion could be explained by an increase in adsorption of metal to the plant material at higher pH values.
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Affiliation(s)
- M Waisberg
- Department of Land Resource Science, University of Guelph, Guelph, Ontario, Canada
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Evenepoel P. Alteration in digestion and absorption of nutrients during profound acid suppression. Best Pract Res Clin Gastroenterol 2001; 15:539-51. [PMID: 11403545 DOI: 10.1053/bega.2000.0197] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Gastric acid suppression therapy has for many years been the cornerstone of the treatment of peptic disease. The availability of more potent inhibitors of gastric acid secretion and the increasing demand for maintenance therapy has renewed interest in the potential side-effects of profound and/or long-lasting therapy. This chapter focuses on the potential interference of gastric acid suppression therapy with the process of the digestion and absorption of nutrients. The theoretical mechanisms by which hypochlorhydria resulting from gastric acid suppression therapy may hamper digestion and absorption are multiple and well documented. Clinical studies evaluating the effect of gastric acid suppression therapy on the assimilation of nutrients are, on the other hand, scarce and have, moreover, yielded conflicting results. The reason for the latter may be related, at least in part, to elements of study design. Data indicating overt malabsorption or clear deficiencies in patients on long-term gastric acid suppression therapy are currently lacking. Nevertheless, it seems prudent, while awaiting the results of additional long-term studies, regularly to monitor these patients, especially those with increased nutrient demand, poor intake or suboptimal stores.
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Affiliation(s)
- P Evenepoel
- Department of Medicine, University Hospital Leuven, Leuven, B-3000, Belgium
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Larsson B, Gritli-Linde A, Norlén P, Lindström E, Håkanson R, Linde A. Extracts of ECL-cell granules/vesicles and of isolated ECL cells from rat oxyntic mucosa evoke a Ca2+ second messenger response in osteoblastic cells. REGULATORY PEPTIDES 2001; 97:153-61. [PMID: 11164951 DOI: 10.1016/s0167-0115(00)00210-x] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/24/2022]
Abstract
Surgical removal of the acid-producing part of the stomach (oxyntic mucosa) reduces bone mass through mechanisms not yet fully understood. The existence of an osteotropic hormone produced by the so-called ECL cells has been suggested. These cells, which are numerous in the oxyntic mucosa, operate under the control of circulating gastrin. Both gastrin and an extract of the oxyntic mucosa decrease blood calcium and stimulate Ca2+ uptake into bone. Conceivably, gastrin lowers blood calcium indirectly by releasing a hypothetical hormone from the ECL cells. The present study investigated, by means of fura-2 fluorometry, the effect of extracts of preparations enriched in ECL cell granules/vesicles from rat oxyntic mucosa on mobilization of intracellular Ca2+ in three osteoblast-like cell lines, UMR-106.01, MC3T3-E1 and Saos-2, and of extracts of isolated ECL cells in UMR-106.01 cells. The extracts were found to induce a dose-related rapid increase in intracellular Ca2+ concentrations in the osteoblast-like cells. The response was not due to histamine or pancreastatin, known ECL cell constituents, and could be abolished by pre-digesting the extracts with exo-aminopeptidase. The results show that the increase in [Ca2+](i) reflects a mobilization of Ca2+ from the endoplasmic reticulum. The observation of an increase in [Ca2+](i) also in murine embryonic fibroblasts show that the response is not limited to osteoblastic cells. The finding that the extracts evoked a typical Ca2+ -mediated second messenger response in osteoblastic cells provides evidence for the existence of a novel osteotropic peptide hormone (gastrocalcin), produced in the ECL cells, and supports the view that gastrectomy-induced osteopathy may reflect a lack of this hormone.
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Affiliation(s)
- B Larsson
- Department of Oral Biochemistry, Göteborg University Box 450, SE-405 30 Göteborg, Sweden
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Sechet A, Hardy P, Hottelart C, Rasombololona M, Abighanem O, Oualim Z, Brazier M, Achard JM, Pruna A, Moriniere P, Fournier A. Role of calcium carbonate administration timing in relation to food intake on its efficiency in controlling hyperphosphatemia in patients on maintenance dialysis. Artif Organs 1998; 22:564-8. [PMID: 9684692 DOI: 10.1046/j.1525-1594.1998.06199.x] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
A study has claimed that at an equal elemental calcium dose, CaCO3 was not less but equally as efficient in controlling predialysis hyperphosphatemia as calcium acetate, provided both calcium salts were ingested 5 min before meals instead of during meals because the higher acidity of the fasting gastric juice would allow for better dissociation of CaCO3. However, this study did not directly demonstrate that the efficiency of CaCO3 in controlling hyperphosphatemia was actually greater when it was administered before a meal than during a meal. To examine this point, we performed a 3 month randomized crossover trial in 12 reliable and stable patients maintained on chronic hemodialysis. Their plasma concentrations of calcium, protein, phosphate, bicarbonate, urea, and creatinine were measured before the first dialysis of each week and the amount of intact parathyroid hormone (PTH) at the beginning and at the end of each of the 3 months. Comparison of the plasma concentrations measured during the 2 modes of administration showed no significant differences in creatinine, urea, bicarbonate, or intact PTH. The mean (+/-SD) plasma concentration of PO4 was not significantly lower (1.88+/-0.50 vs. 1.74+/-0.41 mM) whereas the corrected level of plasma Ca was significantly lower (2.30+/-0.17 vs. 2.38+/-0.16 mM; p < 0.04) when CaCO3 was given before meals than during meals. In conclusion, the administration of CaCO3 before a meal does not increase its efficiency in controlling hyperphosphatemia because the level of plasma PO4 was actually slightly higher with this timing of administration whereas the comparison of the creatinine and urea levels suggested a stability of phosphate intake and the comparison of the PTH and bicarbonate levels suggested the stability of osteolysis and of the transcellular membrane shift of phosphate. Also, administration of CaCO3 before a meal is associated with significantly lower plasma corrected calcium, suggesting less absorption of calcium, which may be an advantage but only in hypercalcemic patients. There is no reason other than the prevention of its hypercalcemic effect to recommend the administration of CaCO3 just before meals rather than during meals.
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Affiliation(s)
- A Sechet
- Nephrology Unit, CHU Amiens, France
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Ohta A, Ohtsuki M, Hosono A, Adachi T, Hara H, Sakata T. Dietary fructooligosaccharides prevent osteopenia after gastrectomy in rats. J Nutr 1998; 128:106-10. [PMID: 9430610 DOI: 10.1093/jn/128.1.106] [Citation(s) in RCA: 45] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023] Open
Abstract
Postgastrectomy osteopenia is observed generally in humans. Fructooligosaccharides increase the absorption of calcium from the large intestine of healthy rats. Thus, we have examined whether they stimulate calcium absorption and prevent osteopenia in rats following total gastrectomy. Rats were subjected to either a sham surgical operation or Billoth II gastrectomy. Seven rats from each surgical treatment group were fed a control diet, and another seven rats of each treatment group were fed a diet containing fructooligosaccharides (75 g/kg diet) for 4 wk. For 5 d each week, feces were collected, and the calcium and phosphorus contents were measured for calculation of the absorption of these minerals. At the end of the experiment, the rats were killed and bones were collected. The net calcium absorption, calcium content and bone mineral density of the femur and tibia in gastrectomized rats fed the control diet were significantly less than those in sham-operated rats fed control diet. The net calcium absorption in rats fed the fructooligosaccharides diet was greater than that in rats fed control diet. Moreover, dietary fructooligosaccharides prevented the decrease in the calcium content and bone mineral density in gastrectomized rats. Dietary fructooligosaccharides enhanced calcium absorption and prevented the changes indicative of postgastrectomy osteopenia such as decreases in bone calcium content and bone mineral density in gastrectomized rats.
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Affiliation(s)
- A Ohta
- Nutritional Science Center, Bioscience Laboratories, Meiji Seika Kaisha, Ltd., Saitama 350-02, Japan
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Hansen C, Werner E, Erbes HJ, Larrat V, Kaltwasser JP. Intestinal calcium absorption from different calcium preparations: influence of anion and solubility. Osteoporos Int 1996; 6:386-93. [PMID: 8931033 DOI: 10.1007/bf01623012] [Citation(s) in RCA: 26] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
Not only is the calcium content of a preparation significant for providing adequate calcium supplementation for the prophylaxis and therapy of osteoporosis, but also its bioavailability is of essential importance. In the present study, the bioavailability of calcium citrate and calcium lactogluconate/carbonate from a therapeutic dose (= 500 mg Ca2+) was compared in men aged between 45 and 60 years on an intra-individual basis. Calcium citrate was administered both as a solution and as a suspension to 18 healthy volunteers. Using a double-isotope method, the intestinal absorption from the three preparations was determined in randomized order at intervals of 2-4 weeks. The stable isotope 44Ca (20 mg), in highly enriched form, was added in each case to the ready-to-drink solutions and, at the same time, a sterile and pyrogen-free solution containing 5 mg of the stable isotope 42Ca was injected intravenously. The intestinal calcium absorption was then determined after 24 h on the basis of the ratio of the two isotopes in the plasma. There was a significantly higher absorption of 29% from the citrate solution than from the lactogluconate/carbonate solution (25%). Absorption from the citrate suspension was similar to that from the lactogluconate/carbonate solution. While no correlation was found between the measured values for calcium absorption from the three preparations and the plasma concentration of 1,25-dihydroxycholecalciferol, significant inverse correlations with the basal parathyroid hormone concentration were observed for the citrate and lactogluconate/ carbonate solution. The results of this study show that quantitative data on intestinal calcium absorption can be obtained without employing radioactive isotopes in humans. Moreover, they show that calcium absorption is not determined only by the solubility and the degree of ionization of the calcium salt administered, but rather that it is of a complex nature.
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Affiliation(s)
- C Hansen
- Klinikum der J.W. Goethe-Universität, Frankfurt am Main, Germany
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47
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Klinge B, Lehto-Axtelius D, Akerman M, Håkanson R. Structure of calvaria after gastrectomy. An experimental study in the rat. Scand J Gastroenterol 1995; 30:952-7. [PMID: 8545614 DOI: 10.3109/00365529509096337] [Citation(s) in RCA: 30] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
BACKGROUND Gastrectomy induces bone loss, suggesting that the stomach is important for calcium homeostasis. In this study we examined the effects of gastrectomy, with or without CaCl2 supplementation, on the structure of the calvaria of the rat. METHODS The calvaria were dissected out and transilluminated, and the calvaria thickness was measured before (micrometer) and after fixation and sectioning (microscopy). Sections of the skull were analysed planimetrically for bone tissue area, using computer-assisted image analysis. RESULTS The time course of the gastrectomy-produced bone loss was studied. After 4 weeks the remaining bone represented about 70% of that in control rats, and after 8 weeks the value was 50%. The thickness of the calvaria was lower in gastrectomized rats than in sham-operated controls. Bone marrow and samples from liver and spleen were examined; no differences were found between experimental and control groups. Daily ingestion of 100 mg CaCl2.2H2O did not prevent the bone loss. CONCLUSIONS It is unlikely that the gastrectomy-produced bone loss reflects calcium deficiency. The results rather support the view that the stomach is important for calcium homeostasis through another mechanism, perhaps involving a hypothetical gastric hormone.
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Affiliation(s)
- B Klinge
- Dept. of Periodontology, University of Lund, Malmö, Sweden
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Serfaty-Lacrosniere C, Wood RJ, Voytko D, Saltzman JR, Pedrosa M, Sepe TE, Russell RR. Hypochlorhydria from short-term omeprazole treatment does not inhibit intestinal absorption of calcium, phosphorus, magnesium or zinc from food in humans. J Am Coll Nutr 1995; 14:364-8. [PMID: 8568113 DOI: 10.1080/07315724.1995.10718522] [Citation(s) in RCA: 110] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
OBJECTIVE Low gastric pH is generally believed to be an important factor in intestinal mineral absorption. Thus, hypochlorhydria could be an important risk factor for mineral malabsorption and the development of marginal mineral status. We studied whether the hypochlorhydria associated with treatment with the anti-ulcer medication omeprazole, a potent gastric proton pump inhibition, would affect intestinal calcium, phosphorus, magnesium, or zinc absorption from food. METHODS Thirteen normal, healthy adults were assigned to either a control group (n = 5) receiving no drug treatment or an omeprazole treatment group (n = 8) to produce increased gastric pH. Omeprazole treatment of normal volunteers resulted in a significant change in postprandial gastric pH (pH 6.4 +/- 0.3 vs. 3.6 +/- 0.5 in control subjects, p < 0.01) and baseline fasting pH (pH 5.8 +/- 0.5 vs. pH 1.8 +/- 0.3 in controls, p < 0.01) after an overnight fast. Net mineral absorption from a standard test meal was measured using a whole gut lavage technique. Mineral absorption was measured twice in each subject, once with 120 mL of 0.1 mol/liter hydrochloric acid and a second time with 120 mL of distilled water alone. RESULTS We found that despite marked changes in gastric pH due to drug treatment or administration of exogenous HCl, no change in the intestinal absorption of calcium, phosphorus, magnesium or zinc from a standard test meal was evident. CONCLUSIONS These findings suggest that changing the gastric pH alone does not modify the net intestinal absorption of several minerals from food. Therefore, it is unlikely that moderate hypochlorhydria resulting from short-term omeprazole treatment substantially increases the risk for developing calcium, phosphorus, magnesium, or zinc deficiencies due to mineral malabsorption.
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Affiliation(s)
- C Serfaty-Lacrosniere
- Tufts University, Mineral Bioavailability Laboratory, USDA Human Nutrition Research Center on Aging, Boston, MA 02111, USA
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Guinotte F, Gautron J, Nys Y, Soumarmon A. Calcium solubilization and retention in the gastrointestinal tract in chicks (Gallus domesticus) as a function of gastric acid secretion inhibition and of calcium carbonate particle size. Br J Nutr 1995; 73:125-39. [PMID: 7857907 DOI: 10.1079/bjn19950014] [Citation(s) in RCA: 67] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
Abstract
In chicks, immature pullets and laying hens, the inhibition of gastric acid secretion by omeprazole, an H+,K(+)-transporting ATPase (EC 3.6.1.36) inhibitor, greatly increased proventricular and gizzard pH values. Consequently, gizzard soluble Ca concentration deceased and the insoluble Ca fraction increased. Inhibition of acid secretion increased duodenal pH values in immature pullets and laying hens but not in chicks. Duodenal soluble and ionic Ca concentrations were lowered by gastric acid inhibition in chicks and to a larger extent in immature pullets and laying hens. The use of Ca of coarse particle size increased the gizzard insoluble Ca fraction in chicks and pullets. However, it did not influence its soluble Ca fraction in chicks but tended to reinforce the negative effect of omeprazole on soluble Ca in the gizzard and duodenum of chicks and laying hens. Coarse particles of Ca led to an increase in gizzard and duodenal soluble Ca at the end of eggshell calcification in laying hens. An enhancement in the level of Ca in the diet from 10 to 36 g/kg increased gizzard soluble Ca and duodenal soluble and ionic Ca concentrations in immature and adult hens. Intestinal Ca retention and bone mineralization was unaffected by gastric acid inhibition in chicks but were largely diminished by the use of coarse particles of Ca. Gastric acid inhibition was associated in laying hens with decreased Ca retention to a small extent and with reduced eggshell quality. These observations confirm that gastric acid secretion is of importance for CaCO3 solubilization but question its role as a prerequisite for intestinal Ca retention in chicks and even in hens fed on a high Ca diet.
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Affiliation(s)
- F Guinotte
- Station de Recherches Avicoles, INRA Centre de Tours, Nouzilly, France
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Abstract
There are more than a dozen commonly prescribed calcium supplements and hundreds of different formulations commercially available. Numerous factors need to be considered when selecting a calcium preparation. Physical properties such as solubility, interference from coingested medications or foodstuffs, dosage, and timing can all affect the bioavailability of calcium. Medical conditions such as lactose intolerance, impaired gastric acid secretion, and high risk profile for kidney stone formation may impact on selection of a calcium supplement. This article will review the available literature and make general recommendations for the optimal use of calcium preparations.
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Affiliation(s)
- D I Levenson
- New York Hospital, Cornell University Medical Center, NY
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