Continuous PPI Treatment after Gastric Bypass Increases the Risk of Pathological PTH Levels at Ten Years Postoperatively

Continuous PPI Treatment after Gastric Bypass Increases the Risk of Pathological PTH Levels at Ten Years Postoperatively | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Continuous PPI Treatment after Gastric Bypass Increases the Risk of Pathological PTH Levels at Ten Years Postoperatively Katharina Stevens, Hella Hultin, Magnus Sundbom This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5383441/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 27 Jan, 2025 Read the published version in Obesity Surgery → Version 1 posted 9 You are reading this latest preprint version Abstract Introduction: Apart from massive weight loss, metabolic and bariatric surgery, especially gastric bypass (RYGBP), can cause nutritional deficiencies. Proton pump inhibitors (PPI), relatively often used after RYGBP, are associated with reduced calcium absorption. We have studied the long-term impact of PPI upon calcium homeostasis among RYGBP patients. Methods: In the Scandinavian Obesity Surgery Registry (SOReg), 550 primary RYGBP patients, with eGFR > 60 ml/min/1.73m2, had PTH and 25-OH D levels registered at 10 years. To avoid the impact of hypovitaminosis D, those with 25-OH D >75 nmol/L were selected. Results: At 10 years, 10.3% of patients reported continuous PPI treatment, i.e., daily use during the last month. In an age adjusted logistic regression model, continuous PPI treatment was associated with a quadruple risk (OR: 4.65 [1.54-14.04]) of having a pathological PTH level (>7 pmol/L). Conclusion: This unique study has shown a correlation between continuous PPI use and pathological PTH levels, thereby inferring that the medication may have detrimental effects upon calcium homeostasis among gastric bypass patients. The risk of having pathological PTH levels was more than tripled among those with PPI treatment, highlighting the importance of specialized follow-up while also suggesting that a limited duration of PPI treatment is preferable. Figures Figure 1 Background In parallel to the obesity epidemic, metabolic and bariatric surgery (MBS) has rocketed. [ 1 ] In a recent systematic review, MBS demonstrated a high remission rate of type 2 diabetes and a clinically significant decrease in other comorbidities. Furthermore, quality of life was improved. [ 2 ] Apart from massive weight loss, MBS is also a known cause of nutritional deficiencies. This creates a steady growth in the population in need of follow-up care. The Roux-en-Y gastric bypass (RYGBP) procedure, commonly used worldwide, entails altering the anatomy of the gastrointestinal tract, leading to a smaller gastric pouch and a bypass of the duodenum and proximal jejunum. Weight loss is achieved partially by rapidly reaching satiety, and partially by hormonal mechanisms due to the altered intestinal passage of ingested nutrients. Previous studies have also shown that rapid gastric emptying is evident after a RYGBP procedure. [ 3 , 4 ] Each of these properties are proposed mechanisms for the vitamin D deficiency and reduced calcium absorption observed in patients after RYGBP. Sequentially, vitamin D deficiency is a known cause of secondary hyperparathyroidism, which can be detrimental to bone health. Previous studies have shown an increase in PTH among RYGBP patients. [ 5 ] In addition, a recent review reported an increased risk for fracture among bariatric patients. [ 6 ] Dyspepsia, often referred to as indigestion, is a common condition, both in patients with obesity and normal-weight individuals, with symptoms including heartburn and stomach pain. [ 7 ] One of the first lines of treatment includes a proton pump inhibitor (PPI), which reduces the amount of gastric acid produced in the stomach. [ 8 ] Several studies have established an association between PPI treatment and high PTH values, although the underlying cause is still uncertain. [ 9 , 10 ] Few studies to our knowledge have examined PTH levels among RYGBP patients with regards to PPI treatment. Aim To study the impact that PPI medications have upon calcium homeostasis among RYGBP patients. Materials and Method Patient data was gathered from the Scandinavian Obesity Surgery Registry (SOReg), a national quality registry of MBS in Sweden since 2007. SOReg contains clinical and laboratory data at baseline and at 1, 2, 5, and 10 years follow up, all with high validity. [ 11 ] As of 2012, data regarding PTH and 25-OH D levels could also be entered into the registry (not mandatory variables). Patients who had undergone a primary RYGBP without reported revisions and eGFR > 60 ml/min/1.73m 2 , as well as had completed their 10-year postoperative follow-up were included (n = 1193). The cohort was further narrowed by those with complete data on PTH and 25-OH D (n = 550), and sequentially those with 25-OH D > 75 nmol/L. Finally, one patient was excluded because of reported parathyroid surgery, leaving a study population of 175 patients. Statistics Data is presented as mean (+/- standard deviation). Means are compared using either the student’s t-test for parametric data or Mann-Whitney U test for nonparametric data. Proportions are tested using Fischer Exact test due to expected counts less than 5. A p < 0.05 was considered statistically significant. Regression models were calculated where PTH was defined as the dependent variable. Independent variables for all models were identified by correlation testing. A binomial logistic regression analysis was performed where the outcome was defined as normal PTH levels (PTH < 7.0 pmol/l) or pathological PTH levels (PTH \(\:\ge\:\) 7 pmol/l). In this analysis, BMI and age were entered as continuous independent variables, however 25-OH D was stratified as either below 100 nmol/l or 100 nmol/l and higher. The adjusted model was performed in a stepwise manner using independent variables that were significant from the unadjusted analyses. Statistical analysis was performed using the SPSS Statistics software (version 17.0; SPSS, Chicago, IL, USA). Results At the 10-year postoperative follow-up 10.3% of patients reported continuous PPI treatment, i.e. daily use during the last month. As presented in Table 1 , significantly higher PTH levels were evident among those with ongoing PPI treatment, as were lower vitamin D levels. Table 1 Comparison of patient demographics, and PTH and Vitamin D levels in patients with and without daily use. PPI treatment (n = 18) No PPI treatment (n = 157) p-value Men/Women % 16.7/83.3 19.8/80.2 1.00 A BMI at 10 yrs 32.3 ± 7.7 30.7 ± 5.6 .385 Age 49.6 ± 12.8 53.4 ± 10.8 .169 PTH 6.56 ± 2.55 5.15 ± 1.95 .006 Vit D 84.2 ± 10.8 90.3 ± 15.2 .049 B A Comparison via Fischer Exact test, B Comparison via Mann-Whitney U test The proportion of patients with PTH levels at or above 7 pmol/L was significantly higher among patients with PPI treatment (p = .018). Regular PPI treatment proved significant in both our simple and adjusted logistic regression model (OR: 4.65 [1.54–14.04]) as did age (OR: 1.05 [1.01–1.09]). Table 2 Logistic Regression Model, Pathological PTH as Dependent Variable Simple Logistic Regression Adjusted Logistic Regression Total (%) Odds Ratio 95% C.I. p-value Odds Ratio 95% C.I. p-value PPI treatment No Yes 157 Ref Ref. 18 3.71 1.30-10.55 0.01 4.65 1.54–14.04 0.01 Age (years) 175 1.041 1.00-1.08 0.04 1.05 1.01–1.09 0.02 BMI (kg/m 2 ) 175 1.073 1.01–1.14 0.03 Sex Male 27 Ref. Female 118 0.752 0.29–1.93 0.55 Vit D (nmol/L) 75–99 139 2.65 .76 − 9.30 0.13 100 and up 36 Ref. Discussion Daily use of PPIs clearly has a measurable impact upon calcium homeostasis among RYGBP patients, evident by the results of this study. Not only were the mean PTH values significantly higher, but the odds of having pathological PTH levels was more than four times greater among those with PPI medications, which is a clear sign of parathyroid activation. Results from previous studies, including work done by our own group, have shown repeatedly that the RYGBP procedure is associated with elevated PTH levels suggesting a negative impact upon calcium homeostasis. [ 12 , 5 ] The fraction of calcium that is absorbed has been shown to decrease significantly after a RYGBP procedure. [ 13 ] Consequentially, when adjusted for other known risk factors for high PTH levels (sex, age, BMI and vitamin D levels) the procedure proves to be a significant factor in itself when predicting elevated PTH levels. Our previous work has also shown that with time since surgery, PTH levels continue to rise even when adjusted for age. [ 12 ] Conclusively, the procedure itself impedes calcium homeostasis which is mirrored by elevated PTH levels. This is presumably (at least in part) due to the excluded portion of the proximal intestine, which is a major site for vitamin D dependent calcium absorption. Studies have shown repeatedly that PPI therapy is associated with reduced calcium absorption. [ 14 , 15 , 16 ] Dating back to the 1950’s, several reports of patients having undergone gastrectomies have shown that reduced gastric acid is linked to osteomalacia. [ 17 , 18 ] Similarly, PPI treatment leads to a reduction in gastric acid, increased levels of gastrin and hypochloridria, all of which are potential causes of elevated PTH levels. [ 19 ] In line with the present study, Fitzpatrick and colleagues recently published a study reporting an OR of 1.6 for developing high PTH levels among non-bariatric patients medicating with PPIs. [ 9 ] The results from this study suggest an even greater risk among those having undergone RYGBP as PPI treatment was associated with an OR of nearly five. A recent meta-analysis of non-operated individuals also reported a greater risk of fracture among those taking PPIs, and concluded caution should be taken when prescribing to patients with other risk factors for osteoporosis. [ 20 ] Noteworthy, RYGBP has repeatedly been identified as a major risk factor for osteoporosis. [ 21 ] Although RYGBP results in a reduced rate of PPI treatment, it is still continuously used by roughly 10% of patients. [ 22 ] The altered anatomy following a RYGBP leads to changes in the gastrointestinal environment. A previous study of the excluded stomach in RYGBP patients, using a percutaneous gastrostomy, showed low acid output with simultaneous PPI treatment. [ 23 ] This implies reduced acidity along the proximal jejunum following the entero-entero anastomosis, which has been illustrated in other published research. [ 3 ] The reduced acidity likely alters the absorption of nutrients, including calcium, as observed in the aforementioned studies. This study underlines PPI treatment as an additional risk factor for pathological calcium homeostasis among RYGBP patients. The elevated PTH levels among RYGBP patients are presumably caused by malabsorption and/or vitamin D deficiency, i.e. secondary hyperparathyroidism. It is however, beyond the scope of this study to specify due to insufficient data. Regardless, it is worth mentioning that secondary hyperparathyroidism is a silent state that can be detrimental to bone health when left untreated. Considering the impaired calcium homeostasis among RYGBP patients, it is especially important to monitor for PTH pathology long term postoperatively, and that this be taken into consideration when prescribing regular PPI treatment. Essentially, this stresses the need for long-term dedicated follow-up of these patients. Strengths and limitations The generalizability of the present results should be high as our patient cohort is very similar to the worldwide data presented in the last IFSO report (n = 480,970 procedures), e.g., proportion of female patients (80% vs. IFSO: 79 [range 60–86]%), median age at surgery (42 vs. 41 [31–45] years), and baseline BMI (42 vs 41 [36–45] kg/m 2 ). [ 24 ] Our study bases PPI treatment upon register data where patients responded whether they had regularly medicated for acid-related symptoms during the past month. Hence, patients with irregular PPI use are likely present in the “no treatment” group. In Sweden, like several other countries, PPI medications are available without a prescription. Thus, it is difficult to determine their use through patient charts and/or prescription registers, and patient reported use is likely a superior source of information. We have also not considered type of PPI nor dosage when drawing conclusions in this study. The fact that we could present significant results despite these drawbacks and the rather low number of patients implies a strong association between continuous PPI use and pathological PTH levels. The lack of data regarding calcium levels halts the ability to decipher the type of pathological hyperparathyroidism observed in this population. However, removing those with low eGFR also excises the patients with elevated PTH levels due to kidney failure. In addition, the PTH levels in both groups, although at the higher end of the normal range, remained lower than levels typical for primary hyperparathyroidism. Conclusion The results from this study has uniquely correlated continuous PPI use among RYGBP patients as a risk factor for pathological PTH levels. This suggests that PPIs and the altered anatomy present a compounded threat to calcium homeostasis. Although the risk of having pathological PTH levels was more than tripled, patients with acid-related symptoms should not be denied PPIs, but the duration of treatment should be limited and specialized follow up long term is key to reduce the risk of bone disease. Declarations Ethical Approval: All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. No funding was received for this study. Consent to Participate: Informed consent does not apply. Conflict of interest: The authors declare no competing interests. References Welbourn R, Hollyman M, Kinsman R, Dixon J, Liem R, Ottosson J, et al. Bariatric surgery worldwide: Baseline Demographic Description and one-year outcomes from the fourth IFSO global registry report 2018. Obesity Surgery. 2018;29:782–95. Raza MM, Njdeaka-Kevin T, Polo J, Azimuddin K. Long-term outcomes of Bariatric Surgery: A systematic review. Cureus. 2023; Ladebo L, Pedersen PV, Pacyk GJ, Kroustrup JP, Drewes AM, Brock C, et al. Gastrointestinal ph, motility patterns, and transit times after roux-en-Y gastric bypass. Obesity Surgery. 2021;31:2632–40. Dirksen C, Damgaard M, Bojsen‐Møller KN, Jørgensen NB, Kielgast U, Jacobsen SH, et al. Fast pouch emptying, delayed small intestinal transit, and exaggerated gut hormone responses after Roux‐en‐Y Gastric Bypass. Neurogastroenterology & Motility. 2013;25:346. Gao Z, Liang Y, Zheng C, Wang Z, Wu Z, Li M, et al. Prevalence and associated factors of secondary hyperparathyroidism after Roux‐en‐Y Gastric Bypass: A meta‐analysis. Obesity Reviews. 2022;23. Paccou J, Tsourdi E, Meier C, Palermo A, Pepe J, Body J-J, et al. Bariatric surgery and Skeletal Health: A Narrative Review and position statement for Management by the European Calcified Tissue Society (ECTS). Bone. 2022;154:116236. Talley NJ, Stanghellini V, Heading RC, Koch KL, Malagelada JR, Tytgat GN. Functional gastroduodenal disorders. Gut. 1999;45:ii37–42. Miwa H, Nagahara A, Asakawa A, Arai M, Oshima T, Kasugai K, et al. Evidence-based clinical practice guidelines for functional dyspepsia 2021. Journal of Gastroenterology. 2022;57:47–61. Fitzpatrick D, Lannon R, Laird E, Ward M, Hoey L, Hughes CF, et al. The association between Proton Pump Inhibitors and hyperparathyroidism: A potential mechanism for increased fracture—results of a large observational cohort study. Osteoporosis International. 2023;34:1917–26. Hinson AM, Wilkerson BM, Rothman‐Fitts I, Riggs AT, Stack BC, Bodenner DL. Hyperparathyroidism associated with long‐term proton pump inhibitors independent of concurrent bisphosphonate therapy in elderly adults. Journal of the American Geriatrics Society. 2015;63:2070–3. Sundbom M, Näslund I, Näslund E, Ottosson J. High acquisition rate and internal validity in the Scandinavian Obesity Surgery Registry. Surgery for Obesity and Related Diseases. 2021;17:606–14. Stevens K, Hultin H, Sundbom M. Hypovitaminosis D and Hyperparathyroidism: A 5-year postoperative follow-up of 30,458 gastric bypass and sleeve gastrectomy patients. Surgery for Obesity and Related Diseases. 2024; Schafer AL, Weaver CM, Black DM, Wheeler AL, Chang H, Szefc GV, et al. Intestinal calcium absorption decreases dramatically after gastric bypass surgery despite optimization of Vitamin D status. Journal of Bone and Mineral Research. 2015;30:1377–85. Corley DA, Kubo A, Zhao W, Quesenberry C. Proton pump inhibitors and histamine-2 receptor antagonists are associated with hip fractures among at-risk patients. Gastroenterology. 2010;139:93–101. Ito T, Jensen RT. Association of long-term proton pump inhibitor therapy with bone fractures and effects on absorption of calcium, vitamin B12, iron, and magnesium. Current Gastroenterology Reports. 2010;12:448–57. Saki F, Shams M, Dastghaib S, Koohpeyma F. Pantoprazole-induced bone loss through gastrin secretion: A stereological study. BioMed Research International. 2023;2023:1–11. Pyrah LN, Smith IrvineB. Osteomalacia following gastrectomy. The Lancet. 1956;267:935–7. Baird IM, Oleesky S. Osteomalacia following gastric surgery. Gastroenterology. 1957;33:284–92. Ali T, Roberts DN, Tierney WM. Long-term safety concerns with proton pump inhibitors. The American Journal of Medicine. 2009;122:896–903. Yu EW, Bauer SR, Bain PA, Bauer DC. Proton pump inhibitors and risk of fractures: A meta-analysis of 11 international studies. The American Journal of Medicine. 2011;124:519–26 Hernández‐Martínez A, Veras L, Boppre G, Soriano‐Maldonado A, Oliveira J, Diniz‐Sousa F, et al. Changes in volumetric bone mineral density and bone quality after Roux‐en‐Y Gastric Bypass: A meta‐analysis with meta‐regression. Obesity Reviews. 2022;23. Elias K, Hedberg J, Sundbom M. Prevalence and impact of acid-related symptoms and diarrhea in patients undergoing roux-en-Y gastric bypass, sleeve gastrectomy, and biliopancreatic diversion with duodenal switch. Surgery for Obesity and Related Diseases. 2020;16:520–7. Sundbom M, Nyman R, Hedenström H, Gustavsson S. Investigation of the excluded stomach after roux-en-Y gastric bypass. Obesity Surgery. 2001;11:25–7. th - IFSO Global Registry Report 2019. IFSO; [cited 2024 May 15]. Available from: https://www.ifso.com/pdf/8th-ifso-registry-report-2023.pdf Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 27 Jan, 2025 Read the published version in Obesity Surgery → Version 1 posted Editorial decision: Revision requested 23 Nov, 2024 Reviews received at journal 20 Nov, 2024 Reviewers agreed at journal 17 Nov, 2024 Reviews received at journal 17 Nov, 2024 Reviewers agreed at journal 17 Nov, 2024 Reviewers invited by journal 16 Nov, 2024 Editor assigned by journal 12 Nov, 2024 Submission checks completed at journal 12 Nov, 2024 First submitted to journal 03 Nov, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-5383441","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":381794998,"identity":"22851e22-d5c1-47b6-83c7-30cc1beb7d0e","order_by":0,"name":"Katharina Stevens","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABAElEQVRIiWNgGAWjYBACCQYGNggFB+wNhLQww7UwQtTyHCBKCwOSFokE/Fok288fe/Bzj0UefwP78wcf22zy5Ge+MZNg+GODU4s0TzK7Yc8ziWKJAzyGjTPb0ooNbueYSTC2peHUIseQzCbBc0AiseEAD2Mzz5nDiRukQVoaDuPWwv+YTfIPUMv8A+wPm/+c+Z84f+YZkMP+43aYRDKbNMiWDQcYDJsZKg4kNtzgAWphO4Db+zMem0nLALVsPMxjOLOnIjlxw5m0YovEtmScWiTOJz6TfHOgLnHe8fYHH34Y2CXObz+88caHP3Y4tSAAMzIngQgNo2AUjIJRMApwAwCeVFM52wCiTwAAAABJRU5ErkJggg==","orcid":"","institution":"Uppsala University Hospital","correspondingAuthor":true,"prefix":"","firstName":"Katharina","middleName":"","lastName":"Stevens","suffix":""},{"id":381794999,"identity":"530504ee-5ecd-4132-b3f1-3c46e3e5033c","order_by":1,"name":"Hella Hultin","email":"","orcid":"","institution":"Karolinska Institutet","correspondingAuthor":false,"prefix":"","firstName":"Hella","middleName":"","lastName":"Hultin","suffix":""},{"id":381795002,"identity":"eac0840b-8caa-4a53-84d8-92c0d838fe58","order_by":2,"name":"Magnus Sundbom","email":"","orcid":"","institution":"Uppsala University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Magnus","middleName":"","lastName":"Sundbom","suffix":""}],"badges":[],"createdAt":"2024-11-03 19:38:10","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5383441/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5383441/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1007/s11695-025-07692-0","type":"published","date":"2025-01-27T15:57:26+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":71634292,"identity":"8acb421d-2ee1-41dc-a2b5-4bd30fdee180","added_by":"auto","created_at":"2024-12-17 09:54:46","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":15282,"visible":true,"origin":"","legend":"\u003cp\u003eProportion of patients with pathological PTH (PTH ≥ 7.0 pmol/L) depending upon PPI treatment\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-5383441/v1/cac895837c43bfd20e7ae6f1.png"},{"id":75351843,"identity":"f8bcc3ba-22b3-4aff-a9a6-83fe493f3ce3","added_by":"auto","created_at":"2025-02-03 16:12:37","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":460923,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5383441/v1/252126b2-229c-45f4-b127-e82698c4d6b9.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Continuous PPI Treatment after Gastric Bypass Increases the Risk of Pathological PTH Levels at Ten Years Postoperatively","fulltext":[{"header":"Background","content":"\u003cp\u003eIn parallel to the obesity epidemic, metabolic and bariatric surgery (MBS) has rocketed. [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e] In a recent systematic review, MBS demonstrated a high remission rate of type 2 diabetes and a clinically significant decrease in other comorbidities. Furthermore, quality of life was improved. [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e] Apart from massive weight loss, MBS is also a known cause of nutritional deficiencies. This creates a steady growth in the population in need of follow-up care.\u003c/p\u003e \u003cp\u003eThe Roux-en-Y gastric bypass (RYGBP) procedure, commonly used worldwide, entails altering the anatomy of the gastrointestinal tract, leading to a smaller gastric pouch and a bypass of the duodenum and proximal jejunum. Weight loss is achieved partially by rapidly reaching satiety, and partially by hormonal mechanisms due to the altered intestinal passage of ingested nutrients. Previous studies have also shown that rapid gastric emptying is evident after a RYGBP procedure. [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e] Each of these properties are proposed mechanisms for the vitamin D deficiency and reduced calcium absorption observed in patients after RYGBP. Sequentially, vitamin D deficiency is a known cause of secondary hyperparathyroidism, which can be detrimental to bone health. Previous studies have shown an increase in PTH among RYGBP patients. [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e] In addition, a recent review reported an increased risk for fracture among bariatric patients. [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eDyspepsia, often referred to as indigestion, is a common condition, both in patients with obesity and normal-weight individuals, with symptoms including heartburn and stomach pain. [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e] One of the first lines of treatment includes a proton pump inhibitor (PPI), which reduces the amount of gastric acid produced in the stomach. [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e] Several studies have established an association between PPI treatment and high PTH values, although the underlying cause is still uncertain. [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e] Few studies to our knowledge have examined PTH levels among RYGBP patients with regards to PPI treatment.\u003c/p\u003e\n\u003ch3\u003eAim\u003c/h3\u003e\n\u003cp\u003eTo study the impact that PPI medications have upon calcium homeostasis among RYGBP patients.\u003c/p\u003e"},{"header":"Materials and Method","content":"\u003cp\u003ePatient data was gathered from the Scandinavian Obesity Surgery Registry (SOReg), a national quality registry of MBS in Sweden since 2007. SOReg contains clinical and laboratory data at baseline and at 1, 2, 5, and 10 years follow up, all with high validity. [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e] As of 2012, data regarding PTH and 25-OH D levels could also be entered into the registry (not mandatory variables). Patients who had undergone a primary RYGBP without reported revisions and eGFR\u0026thinsp;\u0026gt;\u0026thinsp;60 ml/min/1.73m\u003csup\u003e2\u003c/sup\u003e, as well as had completed their 10-year postoperative follow-up were included (n\u0026thinsp;=\u0026thinsp;1193). The cohort was further narrowed by those with complete data on PTH and 25-OH D (n\u0026thinsp;=\u0026thinsp;550), and sequentially those with 25-OH D\u0026thinsp;\u0026gt;\u0026thinsp;75 nmol/L. Finally, one patient was excluded because of reported parathyroid surgery, leaving a study population of 175 patients.\u003c/p\u003e \u003cp\u003eStatistics\u003c/p\u003e \u003cp\u003eData is presented as mean (+/- standard deviation). Means are compared using either the student\u0026rsquo;s t-test for parametric data or Mann-Whitney U test for nonparametric data. Proportions are tested using Fischer Exact test due to expected counts less than 5. A p\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered statistically significant. Regression models were calculated where PTH was defined as the dependent variable. Independent variables for all models were identified by correlation testing. A binomial logistic regression analysis was performed where the outcome was defined as normal PTH levels (PTH\u0026thinsp;\u0026lt;\u0026thinsp;7.0 pmol/l) or pathological PTH levels (PTH \u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:\\ge\\:\\)\u003c/span\u003e\u003c/span\u003e 7 pmol/l). In this analysis, BMI and age were entered as continuous independent variables, however 25-OH D was stratified as either below 100 nmol/l or 100 nmol/l and higher. The adjusted model was performed in a stepwise manner using independent variables that were significant from the unadjusted analyses. Statistical analysis was performed using the SPSS Statistics software (version 17.0; SPSS, Chicago, IL, USA).\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eAt the 10-year postoperative follow-up 10.3% of patients reported continuous PPI treatment, i.e. daily use during the last month. As presented in Table \u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e, significantly higher PTH levels were evident among those with ongoing PPI treatment, as were lower vitamin D levels.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eComparison of patient demographics, and PTH and Vitamin D levels in patients with and without daily use.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePPI treatment\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;18)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNo PPI treatment\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;157)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003ep-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMen/Women %\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e16.7/83.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e19.8/80.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.00 \u003csup\u003eA\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBMI at 10 yrs\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e32.3\u0026thinsp;\u0026plusmn;\u0026thinsp;7.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e30.7\u0026thinsp;\u0026plusmn;\u0026thinsp;5.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e.385\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e49.6\u0026thinsp;\u0026plusmn;\u0026thinsp;12.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e53.4\u0026thinsp;\u0026plusmn;\u0026thinsp;10.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e.169\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePTH\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e6.56\u0026thinsp;\u0026plusmn;\u0026thinsp;2.55\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e5.15\u0026thinsp;\u0026plusmn;\u0026thinsp;1.95\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e.006\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVit D\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e84.2\u0026thinsp;\u0026plusmn;\u0026thinsp;10.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e90.3\u0026thinsp;\u0026plusmn;\u0026thinsp;15.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e.049 \u003csup\u003eB\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003csup\u003eA\u003c/sup\u003e Comparison via Fischer Exact test, \u003csup\u003eB\u003c/sup\u003e Comparison via Mann-Whitney U test\u003c/p\u003e \u003cp\u003eThe proportion of patients with PTH levels at or above 7 pmol/L was significantly higher among patients with PPI treatment (p\u0026thinsp;=\u0026thinsp;.018).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eRegular PPI treatment proved significant in both our simple and adjusted logistic regression model (OR: 4.65 [1.54\u0026ndash;14.04]) as did age (OR: 1.05 [1.01\u0026ndash;1.09]).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eLogistic Regression Model, Pathological PTH as Dependent Variable\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"9\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"4\" nameend=\"c6\" namest=\"c3\"\u003e \u003cp\u003eSimple Logistic Regression\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c9\" namest=\"c7\"\u003e \u003cp\u003eAdjusted Logistic Regression\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eTotal (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eOdds Ratio\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e95% C.I.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003ep-value\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eOdds Ratio\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e95% C.I.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003ep-value\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePPI treatment\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" morerows=\"1\" nameend=\"c2\" namest=\"c1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cb\u003eNo\u003c/b\u003e\u003c/p\u003e \u003cp\u003e\u003cb\u003eYes\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e157\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eRef\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eRef.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.71\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.30-10.55\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.01\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e4.65\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e1.54\u0026ndash;14.04\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.01\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAge (years)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e175\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.041\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.00-1.08\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.04\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1.05\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e1.01\u0026ndash;1.09\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.02\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eBMI (kg/m\u003c/b\u003e\u003csup\u003e\u003cb\u003e2\u003c/b\u003e\u003c/sup\u003e\u003cb\u003e)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e175\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.073\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.01\u0026ndash;1.14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.03\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSex\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eMale\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e27\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eRef.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eFemale\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e118\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.752\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.29\u0026ndash;1.93\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.55\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eVit D (nmol/L)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003e75\u0026ndash;99\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e139\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.65\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e.76\u0026thinsp;\u0026minus;\u0026thinsp;9.30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003e100 and up\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e36\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eRef.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eDaily use of PPIs clearly has a measurable impact upon calcium homeostasis among RYGBP patients, evident by the results of this study. Not only were the mean PTH values significantly higher, but the odds of having pathological PTH levels was more than four times greater among those with PPI medications, which is a clear sign of parathyroid activation.\u003c/p\u003e \u003cp\u003eResults from previous studies, including work done by our own group, have shown repeatedly that the RYGBP procedure is associated with elevated PTH levels suggesting a negative impact upon calcium homeostasis. [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e] The fraction of calcium that is absorbed has been shown to decrease significantly after a RYGBP procedure. [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e] Consequentially, when adjusted for other known risk factors for high PTH levels (sex, age, BMI and vitamin D levels) the procedure proves to be a significant factor in itself when predicting elevated PTH levels. Our previous work has also shown that with time since surgery, PTH levels continue to rise even when adjusted for age. [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e] Conclusively, the procedure itself impedes calcium homeostasis which is mirrored by elevated PTH levels. This is presumably (at least in part) due to the excluded portion of the proximal intestine, which is a major site for vitamin D dependent calcium absorption.\u003c/p\u003e \u003cp\u003eStudies have shown repeatedly that PPI therapy is associated with reduced calcium absorption. [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e] Dating back to the 1950\u0026rsquo;s, several reports of patients having undergone gastrectomies have shown that reduced gastric acid is linked to osteomalacia. [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e] Similarly, PPI treatment leads to a reduction in gastric acid, increased levels of gastrin and hypochloridria, all of which are potential causes of elevated PTH levels. [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e] In line with the present study, Fitzpatrick and colleagues recently published a study reporting an OR of 1.6 for developing high PTH levels among non-bariatric patients medicating with PPIs. [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e] The results from this study suggest an even greater risk among those having undergone RYGBP as PPI treatment was associated with an OR of nearly five. A recent meta-analysis of non-operated individuals also reported a greater risk of fracture among those taking PPIs, and concluded caution should be taken when prescribing to patients with other risk factors for osteoporosis. [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e] Noteworthy, RYGBP has repeatedly been identified as a major risk factor for osteoporosis. [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e] Although RYGBP results in a reduced rate of PPI treatment, it is still continuously used by roughly 10% of patients. [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eThe altered anatomy following a RYGBP leads to changes in the gastrointestinal environment. A previous study of the excluded stomach in RYGBP patients, using a percutaneous gastrostomy, showed low acid output with simultaneous PPI treatment. [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e] This implies reduced acidity along the proximal jejunum following the entero-entero anastomosis, which has been illustrated in other published research. [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e] The reduced acidity likely alters the absorption of nutrients, including calcium, as observed in the aforementioned studies. This study underlines PPI treatment as an additional risk factor for pathological calcium homeostasis among RYGBP patients.\u003c/p\u003e \u003cp\u003eThe elevated PTH levels among RYGBP patients are presumably caused by malabsorption and/or vitamin D deficiency, i.e. secondary hyperparathyroidism. It is however, beyond the scope of this study to specify due to insufficient data. Regardless, it is worth mentioning that secondary hyperparathyroidism is a silent state that can be detrimental to bone health when left untreated. Considering the impaired calcium homeostasis among RYGBP patients, it is especially important to monitor for PTH pathology long term postoperatively, and that this be taken into consideration when prescribing regular PPI treatment. Essentially, this stresses the need for long-term dedicated follow-up of these patients.\u003c/p\u003e"},{"header":"Strengths and limitations","content":"\u003cp\u003eThe generalizability of the present results should be high as our patient cohort is very similar to the worldwide data presented in the last IFSO report (n\u0026thinsp;=\u0026thinsp;480,970 procedures), e.g., proportion of female patients (80% \u003cem\u003evs.\u003c/em\u003e IFSO: 79 [range 60\u0026ndash;86]%), median age at surgery (42 \u003cem\u003evs.\u003c/em\u003e 41 [31\u0026ndash;45] years), and baseline BMI (42 vs 41 [36\u0026ndash;45] kg/m\u003csup\u003e2\u003c/sup\u003e). [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eOur study bases PPI treatment upon register data where patients responded whether they had regularly medicated for acid-related symptoms during the past month. Hence, patients with irregular PPI use are likely present in the \u0026ldquo;no treatment\u0026rdquo; group. In Sweden, like several other countries, PPI medications are available without a prescription. Thus, it is difficult to determine their use through patient charts and/or prescription registers, and patient reported use is likely a superior source of information. We have also not considered type of PPI nor dosage when drawing conclusions in this study. The fact that we could present significant results despite these drawbacks and the rather low number of patients implies a strong association between continuous PPI use and pathological PTH levels.\u003c/p\u003e \u003cp\u003eThe lack of data regarding calcium levels halts the ability to decipher the type of pathological hyperparathyroidism observed in this population. However, removing those with low eGFR also excises the patients with elevated PTH levels due to kidney failure. In addition, the PTH levels in both groups, although at the higher end of the normal range, remained lower than levels typical for primary hyperparathyroidism.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThe results from this study has uniquely correlated continuous PPI use among RYGBP patients as a risk factor for pathological PTH levels. This suggests that PPIs and the altered anatomy present a compounded threat to calcium homeostasis. Although the risk of having pathological PTH levels was more than tripled, patients with acid-related symptoms should not be denied PPIs, but the duration of treatment should be limited and specialized follow up long term is key to reduce the risk of bone disease.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eEthical Approval: All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. No funding was received for this study.\u003c/p\u003e\n\u003cp\u003eConsent to Participate: Informed consent does not apply.\u003c/p\u003e\n\u003cp\u003eConflict of interest: The authors declare no competing interests.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eWelbourn R, Hollyman M, Kinsman R, Dixon J, Liem R, Ottosson J, et al. Bariatric surgery worldwide: Baseline Demographic Description and one-year outcomes from the fourth IFSO global registry report 2018. Obesity Surgery. 2018;29:782\u0026ndash;95. \u003c/li\u003e\n\u003cli\u003eRaza MM, Njdeaka-Kevin T, Polo J, Azimuddin K. Long-term outcomes of Bariatric Surgery: A systematic review. Cureus. 2023; \u003c/li\u003e\n\u003cli\u003eLadebo L, Pedersen PV, Pacyk GJ, Kroustrup JP, Drewes AM, Brock C, et al. Gastrointestinal ph, motility patterns, and transit times after roux-en-Y gastric bypass. Obesity Surgery. 2021;31:2632\u0026ndash;40. \u003c/li\u003e\n\u003cli\u003eDirksen C, Damgaard M, Bojsen‐M\u0026oslash;ller KN, J\u0026oslash;rgensen NB, Kielgast U, Jacobsen SH, et al. Fast pouch emptying, delayed small intestinal transit, and exaggerated gut hormone responses after Roux‐en‐Y Gastric Bypass. Neurogastroenterology \u0026amp;amp; Motility. 2013;25:346.\u003c/li\u003e\n\u003cli\u003eGao Z, Liang Y, Zheng C, Wang Z, Wu Z, Li M, et al. Prevalence and associated factors of secondary hyperparathyroidism after Roux‐en‐Y Gastric Bypass: A meta‐analysis. Obesity Reviews. 2022;23.\u003c/li\u003e\n\u003cli\u003ePaccou J, Tsourdi E, Meier C, Palermo A, Pepe J, Body J-J, et al. Bariatric surgery and Skeletal Health: A Narrative Review and position statement for Management by the European Calcified Tissue Society (ECTS). Bone. 2022;154:116236. \u003c/li\u003e\n\u003cli\u003eTalley NJ, Stanghellini V, Heading RC, Koch KL, Malagelada JR, Tytgat GN. Functional gastroduodenal disorders. Gut. 1999;45:ii37\u0026ndash;42. \u003c/li\u003e\n\u003cli\u003eMiwa H, Nagahara A, Asakawa A, Arai M, Oshima T, Kasugai K, et al. Evidence-based clinical practice guidelines for functional dyspepsia 2021. Journal of Gastroenterology. 2022;57:47\u0026ndash;61. \u003c/li\u003e\n\u003cli\u003eFitzpatrick D, Lannon R, Laird E, Ward M, Hoey L, Hughes CF, et al. The association between Proton Pump Inhibitors and hyperparathyroidism: A potential mechanism for increased fracture\u0026mdash;results of a large observational cohort study. Osteoporosis International. 2023;34:1917\u0026ndash;26. \u003c/li\u003e\n\u003cli\u003eHinson AM, Wilkerson BM, Rothman‐Fitts I, Riggs AT, Stack BC, Bodenner DL. Hyperparathyroidism associated with long‐term proton pump inhibitors independent of concurrent bisphosphonate therapy in elderly adults. Journal of the American Geriatrics Society. 2015;63:2070\u0026ndash;3. \u003c/li\u003e\n\u003cli\u003eSundbom M, N\u0026auml;slund I, N\u0026auml;slund E, Ottosson J. High acquisition rate and internal validity in the Scandinavian Obesity Surgery Registry. Surgery for Obesity and Related Diseases. 2021;17:606\u0026ndash;14.\u003c/li\u003e\n\u003cli\u003eStevens K, Hultin H, Sundbom M. Hypovitaminosis D and Hyperparathyroidism: A 5-year postoperative follow-up of 30,458 gastric bypass and sleeve gastrectomy patients. Surgery for Obesity and Related Diseases. 2024; \u003c/li\u003e\n\u003cli\u003eSchafer AL, Weaver CM, Black DM, Wheeler AL, Chang H, Szefc GV, et al. Intestinal calcium absorption decreases dramatically after gastric bypass surgery despite optimization of Vitamin D status. Journal of Bone and Mineral Research. 2015;30:1377\u0026ndash;85.\u003c/li\u003e\n\u003cli\u003eCorley DA, Kubo A, Zhao W, Quesenberry C. Proton pump inhibitors and histamine-2 receptor antagonists are associated with hip fractures among at-risk patients. Gastroenterology. 2010;139:93\u0026ndash;101. \u003c/li\u003e\n\u003cli\u003eIto T, Jensen RT. Association of long-term proton pump inhibitor therapy with bone fractures and effects on absorption of calcium, vitamin B12, iron, and magnesium. Current Gastroenterology Reports. 2010;12:448\u0026ndash;57. \u003c/li\u003e\n\u003cli\u003eSaki F, Shams M, Dastghaib S, Koohpeyma F. Pantoprazole-induced bone loss through gastrin secretion: A stereological study. BioMed Research International. 2023;2023:1\u0026ndash;11. \u003c/li\u003e\n\u003cli\u003ePyrah LN, Smith IrvineB. Osteomalacia following gastrectomy. The Lancet. 1956;267:935\u0026ndash;7. \u003c/li\u003e\n\u003cli\u003eBaird IM, Oleesky S. Osteomalacia following gastric surgery. Gastroenterology. 1957;33:284\u0026ndash;92.\u003c/li\u003e\n\u003cli\u003eAli T, Roberts DN, Tierney WM. Long-term safety concerns with proton pump inhibitors. The American Journal of Medicine. 2009;122:896\u0026ndash;903. \u003c/li\u003e\n\u003cli\u003eYu EW, Bauer SR, Bain PA, Bauer DC. Proton pump inhibitors and risk of fractures: A meta-analysis of 11 international studies. The American Journal of Medicine. 2011;124:519\u0026ndash;26 \u003c/li\u003e\n\u003cli\u003eHern\u0026aacute;ndez‐Mart\u0026iacute;nez A, Veras L, Boppre G, Soriano‐Maldonado A, Oliveira J, Diniz‐Sousa F, et al. Changes in volumetric bone mineral density and bone quality after Roux‐en‐Y Gastric Bypass: A meta‐analysis with meta‐regression. Obesity Reviews. 2022;23. \u003c/li\u003e\n\u003cli\u003eElias K, Hedberg J, Sundbom M. Prevalence and impact of acid-related symptoms and diarrhea in patients undergoing roux-en-Y gastric bypass, sleeve gastrectomy, and biliopancreatic diversion with duodenal switch. Surgery for Obesity and Related Diseases. 2020;16:520\u0026ndash;7. \u003c/li\u003e\n\u003cli\u003eSundbom M, Nyman R, Hedenstr\u0026ouml;m H, Gustavsson S. Investigation of the excluded stomach after roux-en-Y gastric bypass. Obesity Surgery. 2001;11:25\u0026ndash;7.\u003c/li\u003e\n\u003cli\u003eth - IFSO Global Registry Report 2019. IFSO; [cited 2024 May 15]. Available from: https://www.ifso.com/pdf/8th-ifso-registry-report-2023.pdf \u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"obesity-surgery","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"obsu","sideBox":"Learn more about [Obesity Surgery](https://link.springer.com/journal/11695)","snPcode":"11695","submissionUrl":"https://submission.springernature.com/new-submission/11695/3","title":"Obesity Surgery","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-5383441/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5383441/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eIntroduction: Apart from massive weight loss, metabolic and bariatric surgery, especially gastric bypass (RYGBP), can cause nutritional deficiencies. Proton pump inhibitors (PPI), relatively often used after RYGBP, are associated with reduced calcium absorption. We have studied the long-term impact of PPI upon calcium homeostasis among RYGBP patients.\u003c/p\u003e\n\u003cp\u003eMethods: In the Scandinavian Obesity Surgery Registry (SOReg), 550 primary RYGBP patients, with eGFR \u0026gt; 60 ml/min/1.73m2, had PTH and 25-OH D levels registered at 10 years. To avoid the impact of hypovitaminosis D, those with 25-OH D \u0026gt;75 nmol/L were selected.\u003c/p\u003e\n\u003cp\u003eResults: At 10 years, 10.3% of patients reported continuous PPI treatment, i.e., daily use during the last month. In an age adjusted logistic regression model, continuous PPI treatment was associated with a quadruple risk (OR: 4.65 [1.54-14.04]) of having a pathological PTH level (\u0026gt;7 pmol/L).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eConclusion: This unique study has shown a correlation between continuous PPI use and pathological PTH levels, thereby inferring that the medication may have detrimental effects upon calcium homeostasis among gastric bypass patients. The risk of having pathological PTH levels was more than tripled among those with PPI treatment, highlighting the importance of specialized follow-up while also suggesting that a limited duration of PPI treatment is preferable.\u003c/p\u003e","manuscriptTitle":"Continuous PPI Treatment after Gastric Bypass Increases the Risk of Pathological PTH Levels at Ten Years Postoperatively","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-12-17 09:54:06","doi":"10.21203/rs.3.rs-5383441/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-11-23T20:26:41+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-11-20T20:34:17+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"201828215675003819693612085842837235735","date":"2024-11-17T15:21:35+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-11-17T12:18:09+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"236899568072831353979554858071744108138","date":"2024-11-17T12:00:00+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-11-16T20:31:59+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-11-12T14:45:33+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-11-12T12:59:16+00:00","index":"","fulltext":""},{"type":"submitted","content":"Obesity Surgery","date":"2024-11-03T19:26:37+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"obesity-surgery","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"obsu","sideBox":"Learn more about [Obesity Surgery](https://link.springer.com/journal/11695)","snPcode":"11695","submissionUrl":"https://submission.springernature.com/new-submission/11695/3","title":"Obesity Surgery","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"1867cf5c-5486-4a42-8e92-778e24a08c30","owner":[],"postedDate":"December 17th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-02-03T16:08:27+00:00","versionOfRecord":{"articleIdentity":"rs-5383441","link":"https://doi.org/10.1007/s11695-025-07692-0","journal":{"identity":"obesity-surgery","isVorOnly":false,"title":"Obesity Surgery"},"publishedOn":"2025-01-27 15:57:26","publishedOnDateReadable":"January 27th, 2025"},"versionCreatedAt":"2024-12-17 09:54:06","video":"","vorDoi":"10.1007/s11695-025-07692-0","vorDoiUrl":"https://doi.org/10.1007/s11695-025-07692-0","workflowStages":[]},"version":"v1","identity":"rs-5383441","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5383441","identity":"rs-5383441","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}