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The Effects of Bariatric Surgery upon the Maintenance of Calcium and Vitamin D Levels
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.ORCID iD: 0000-0001-8274-8247
2024 (English)Doctoral thesis, comprehensive summary (Other academic)
Description
Abstract [en]

Obesity is a growing pandemic, and consequently the population that has undergone a bariatric procedure is steadily rising. Through various mechanisms, bariatric surgery alters the gastrointestinal anatomy, thereby obtaining weight loss while being associated with various nutrient deficiencies including vitamin D. Over time, vitamin D deficiency may lead to elevated levels of parathyroid hormone (PTH) and the depletion of bone, in order to maintain circulating calcium levels. 

The aim of this thesis was to study the effects of bariatric surgery upon calcium homeostasis. In paper I we sought to investigate whether lifestyle factors could explain the difference in bone mineral density (BMD) seen among Roux-en-Y gastric bypass (RYGBP) patients. The second paper is a population-based study that examines the postoperative trends of vitamin D and PTH among patients that have undergone either a RYGBP or a sleeve gastrectomy (SG) (the two currently most popular bariatric procedures worldwide). In paper III the purpose was to explore whether medications to treat dyspepsia had an impact upon calcium homeostasis postoperatively among RYGBP patients. And finally, the purpose of the fourth paper was to study an intramuscular injection as an alternative method for the treatment of vitamin D deficiency among patients who had undergone a biliopancreatic diversion/duodenal switch (BPD/DS) procedure. 

The results from paper I do not indicate that lifestyle factors are a cause of the reduced BMD observed after a RYGBP, therefore the procedure itself is a likely cause of reduced BMD. The analysis conducted in paper II points to the impact that bariatric procedures (specifically RYGBP and SG) have over time regarding vitamin D deficiency. The results showed both differences between procedures as well as a successive decline in vitamin D parallelled by a rise in PTH with time after surgery. In paper III our results indicate that regular PPI therapy is strongly associated with a much higher incidence of pathological PTH levels, suggesting that the combination of the procedure and the medication may have deleterious effects upon calcium homeostasis. Finally, when managing vitamin D deficiency after a BPD/DS procedure, we showed that intramuscular injections had a substantial effect upon both vitamin D levels and PTH levels. 

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2024. , p. 65
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 2063
Keywords [en]
Bariatric surgery, Hypovitaminosis D, Obesity
National Category
Surgery
Identifiers
URN: urn:nbn:se:uu:diva-533180ISBN: 978-91-513-2173-8 (print)OAI: oai:DiVA.org:uu-533180DiVA, id: diva2:1876670
Public defence
2024-09-20, Enghoffsalen, Akademiska Sjukhuset ing 50, Uppsala, 09:00 (Swedish)
Opponent
Supervisors
Available from: 2024-08-30 Created: 2024-06-24 Last updated: 2024-08-30
List of papers
1. Low bone mineral density following gastric bypass is not explained by lifestyle and lack of exercise
Open this publication in new window or tab >>Low bone mineral density following gastric bypass is not explained by lifestyle and lack of exercise
2021 (English)In: BMC Surgery, E-ISSN 1471-2482, Vol. 21, no 1, article id 282Article in journal (Refereed) Published
Abstract [en]

Background

Bariatric surgery, Roux-en-Y gastric bypass (RYGBP) in particular, is associated with weight loss as well as low bone mineral density. Bone mineral density relies upon multiple factors, some of which are lifestyle factors. The aim of this study was to compare lifestyle factors in order to eliminate them as culprits of the suspected difference in BMD in RYGBP operated and controls.

Materials and methods

Study participants included 71 RYGBP-operated women (42.3 years, BMI 33.1 kg/m2) and 94 controls (32.4 years, BMI 23.9 kg/m2). Each completed a DEXA scan, as well as survey of lifestyle factors (e.g. physical activity in daily life, corticosteroid use, and calcium intake). All study participants were premenopausal Caucasian women living in the same area. Blood samples were taken in RYGBP-patients.

Results

BMD was significantly lower in RYGBP, femoral neck 0.98 vs. 1.04 g/cm2 compared to controls, despite higher BMI (present and at 20 years of age) and similar physical activity and calcium intake. In a multivariate analysis, increased time since surgery and age were negatively associated with BMD of the femoral neck and total hip in RYGBP patients.

Conclusion

Despite similar lifestyle, RYGBP was followed by a lower BMD compared to controls. Thus, the reduced BMD in RYGBP cannot be explained, seemingly nor prevented, by lifestyle factors. As the reduction in BMD was associated with time since surgery, strict follow-up is a lifelong necessity after bariatric surgery, and especially important in younger bariatric patients.

Place, publisher, year, edition, pages
BioMed Central (BMC), 2021
Keywords
Bone mineral density, Gastric bypass, Vitamin D, Lifestyle, Long-term results
National Category
Surgery
Identifiers
urn:nbn:se:uu:diva-447950 (URN)10.1186/s12893-021-01281-5 (DOI)000660875600002 ()34088293 (PubMedID)
Available from: 2021-07-01 Created: 2021-07-01 Last updated: 2024-07-04Bibliographically approved
2. Hypovitaminosis D and hyperparathyroidism: a 5-year postoperative follow-up of 30,458 gastric bypass and sleeve gastrectomy patients
Open this publication in new window or tab >>Hypovitaminosis D and hyperparathyroidism: a 5-year postoperative follow-up of 30,458 gastric bypass and sleeve gastrectomy patients
2024 (English)In: Surgery for Obesity and Related Diseases, ISSN 1550-7289, E-ISSN 1878-7533, Vol. 20, no 8, p. 745-751Article in journal (Refereed) Published
Abstract [en]

Background: Bariatric procedures are associated with nutrient deficiencies. Studies show an association between gastric bypass (Roux-en-Y gastric bypass [RYGB]) and hypovitaminosis D as well as hyperparathyroidism, yet few compare RYGB to sleeve gastrectomy (SG), and large long-term analyses are scarce.

Objective: Evaluate trends of vitamin D and parathyroid hormone (PTH) levels in RYGB and SG.

Setting: National quality register.

Method: The Scandinavian Obesity Surgery Registry records all bariatric surgeries in Sweden. Data from 2008 to 2021 on primary RYGB or SG with reported 25-hydroxy vitamin D (25-OH-D) and/or PTH levels were included. Individuals with an estimated glomerular filtration rate of < 60 mL/min/ 1.73 m2 2 were excluded, leaving a study population of 25,385 RYGB and 5073 SG patients.

Results: A decrease in 25-OH-D, mirrored by an increase in PTH, was observed after the first year for both procedures, but more pronounced in RYGB. At 5 years, 25-OH-D levels were still higher than at baseline. Regular supplementation resulted in better 25-OH-D and PTH levels. Linear regression found that procedure type (RYGB versus SG), 25-OH-D levels, and time since surgery were significant factors in predicting PTH levels. The risk of pathologic PTH levels (>7 > 7 pmol/L) at 2 and 5 years postoperatively was roughly three times higher in RYGB (odds ratios 5 3.41 and 2.84, respectively).

Conclusions: Previous studies alongside these results suggest that RYGB, more so than SG, may cause hypovitaminosis D and thereby hyperparathyroidism, which could lead to osteopenia. The threshold for 25-OH-D should be > 75 nmol/L, and despite higher levels, current vitamin D supplementation may not be sufficient. Follow-up should include screening for hyperparathyroidism and hypovitaminosis D.

Place, publisher, year, edition, pages
Elsevier, 2024
National Category
Clinical Medicine Endocrinology and Diabetes Surgery
Identifiers
urn:nbn:se:uu:diva-527773 (URN)10.1016/j.soard.2024.02.004 (DOI)001298688500001 ()38614927 (PubMedID)
Available from: 2024-05-08 Created: 2024-05-08 Last updated: 2024-09-20Bibliographically approved
3. Continuous PPI Treatment After Gastric Bypass Increases the Risk of Pathological PTH Levels at 10 Years Postoperatively
Open this publication in new window or tab >>Continuous PPI Treatment After Gastric Bypass Increases the Risk of Pathological PTH Levels at 10 Years Postoperatively
2025 (English)In: Obesity Surgery, ISSN 0960-8923, E-ISSN 1708-0428, Vol. 35, no 3, p. 941-945Article in journal (Refereed) Published
Abstract [en]

Background

Apart from massive weight loss, metabolic and bariatric surgery, especially gastric bypass (Roux-en-Y gastric bypass [RYGB]), can cause nutritional deficiencies. Proton pump inhibitors (PPI), relatively often used after RYGB, are associated with reduced calcium absorption. We have studied the long-term impact of PPI upon calcium homeostasis among RYGB patients.

Methods

In the Scandinavian Obesity Surgery Registry (SOReg), 550 primary RYGB patients, with eGFR > 60 mL/min/1.73 m2, 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.

Place, publisher, year, edition, pages
Springer, 2025
Keywords
Gastric bypass, Bariatric surgery, Parathyroid hormone, Proton-pump inhibitors
National Category
Surgery Gastroenterology and Hepatology
Identifiers
urn:nbn:se:uu:diva-533131 (URN)10.1007/s11695-025-07692-0 (DOI)001406591600001 ()39865206 (PubMedID)2-s2.0-85217255460 (Scopus ID)
Funder
Uppsala University
Available from: 2024-06-24 Created: 2024-06-24 Last updated: 2025-05-20Bibliographically approved
4. Cholecalciferol Injections Are Effective in Hypovitaminosis D After Duodenal Switch: a Randomized Controlled Study
Open this publication in new window or tab >>Cholecalciferol Injections Are Effective in Hypovitaminosis D After Duodenal Switch: a Randomized Controlled Study
2018 (English)In: Obesity Surgery, ISSN 0960-8923, E-ISSN 1708-0428, Vol. 28, no 10, p. 3007-3011Article in journal (Refereed) Published
Abstract [en]

Background: By treating obesity, one of the major epidemics of this past century, through bariatric surgery, we may cause complications due to malnourishment in a growing population. At present, vitamin D deficiency is of interest, especially in patients with inferior absorption of fat-soluble nutrients after biliopancreatic diversion with duodenal switch (BPD/DS).

Methods: Twenty BPD/DS patients, approximately 4 years postoperatively, were randomized to either intramuscular supplementation of vitamin D with a single dose of 600,000 IU cholecalciferol, or a control group. Patients were instructed to limit their supplementation to 1400 IU of vitamin D and to avoid the influence of UV-B radiation; the study was conducted when sunlight is limited (December to May).

Results: Despite oral supplementation, a pronounced deficiency in vitamin D was seen (injection 19.3; control 23.2 nmol/l) in both groups. The cholecalciferol injection resulted in elevated 25[OH]D levels at 1 month (65.4 nmol/l), which was maintained at 6 months (67.4 nmol/l). This resulted in normalization of intact parathyroid hormone (PTH) levels. No changes in vitamin D or PTH occurred in the control group.

Conclusions: In BPD/DS patients, having hypovitaminosis D despite full oral supplementation, a single injection of 600,000 IU of cholecalciferol was effective in elevating vitamin D levels and normalizing levels of intact PTH. The treatment is simple and highly effective and thus recommended, especially in cases of reduced UV-B radiation.

Keywords
Hypovitaminosis D, Cholecalciferol, Biliopancreatic diversion, Duodenal switch
National Category
Surgery
Identifiers
urn:nbn:se:uu:diva-366951 (URN)10.1007/s11695-018-3307-8 (DOI)000444768500004 ()29869004 (PubMedID)
Available from: 2018-11-28 Created: 2018-11-28 Last updated: 2024-06-24Bibliographically approved

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