Vitamin D status and supplementation before and after Bariatric Surgery: Recommendations based on a systematic review and meta-analysis.

Bariatric surgery is associated with a postoperative reduction of 25(OH) vitamin D levels (25(OH)D) and with skeletal complications. Currently, guidelines for 25(OH)D assessment and vitamin D supplementation in bariatric patients, pre- and post-surgery, are still lacking. The aim of this work is to analyse systematically the published experience on 25(OH)D status and vitamin D supplementation, pre- and post-surgery, and to propose, on this basis, recommendations for management. Preoperatively, 18 studies including 2,869 patients were evaluated. Prevalence of vitamin D insufficiency as defined by 25(OH)D < 30 ng/mL (75 nmol/L) was 85%, whereas when defined by 25(OH)D < 20 ng/mL (50 nmol/L) was 57%. The median preoperative 25(OH)D level was 19.75 ng/mL. After surgery, 39 studies including 5,296 patients were analysed and among those undergoing either malabsorptive or restrictive procedures, a lower rate of vitamin D insufficiency and higher 25(OH)D levels postoperatively were observed in patients treated with high-dose oral vitamin D supplementation, defined as ≥ 2,000 IU/daily (mostly D3-formulation), compared with low-doses (< 2,000 IU/daily). Our recommendations based on this systematic review and meta-analysis should help clinical practice in the assessment and management of vitamin D status before and after bariatric surgery. Assessment of vitamin D should be performed pre- and postoperatively in all patients undergoing bariatric surgery. Regardless of the type of procedure, high-dose supplementation is recommended in patients after bariatric surgery.

A suggested protocol for the endocrine postoperative management of patients undergoing pituitary surgery.

PURPOSE: Endocrine disorders are the most frequent postoperative complications in patients undergoing pituitary surgery. Given the absence of recent guidelines on the postoperative care following pituitary surgery, this article summarizes the available evidence on the topic. METHOD: We conducted a systematic search of PubMed up to 2021 and updated the search in December 2022. We retrieved 119 articles and included 53 full-text papers. RESULTS: The early postoperative care consists of the assessment for cortisol deficiency and diabetes insipidus (DI). Experts suggest that all patients should receive a glucocorticoid (GC) stress dose followed by a rapid taper. The decision for GC replacement after discharge depends on the morning plasma cortisol level on day 3 after surgery. Experts suggest that patients with a morning plasma cortisol<10 mcg/dL should receive GC replacement at discharge, and those with 10-18 mcg/dL a morning dose only, with formal assessment of the hypothalamic-pituitary-adrenal axis at week 6 postoperatively. When the cortisol level is>18 mcg/dL, the patient can be discharged safely without GC, as suggested by observational studies. Postoperative care also includes a close monitoring of water balance. If DI develops, desmopressin is used only in case of uncomfortable polyuria or hypernatremia. The assessment of other hormones is indicated at 3 months postoperatively and beyond. CONCLUSION: The evaluation and treatment of patients following pituitary surgery are based on expert opinion and a few observational studies. Further research is needed to provide additional evidence on the most appropriate approach.

Effect of antiresorptive therapy on aromatase inhibitor induced bone loss in postmenopausal women with early-stage breast cancer: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Aromatase inhibitors (AIs) are routinely used to treat postmenopausal women with early-stage breast cancer. Although AIs improve breast cancer outcomes, they increase the risk of osteoporosis and fractures. This systematic review and meta-analysis assesses the effect of antiresorptive drugs on AI induced bone loss in postmenopausal women with non-metastatic breast cancer. METHODS: We searched four databases until November 4th 2020. We included Randomized controlled trials (RCTs) of antiresorptive drugs in postmenopausal women with breast cancer treated with AI. Two authors screened studies, extracted data and assessed the risk of bias independently and in duplicate. RESULTS: We identified 14 RCTs: 7 on zoledronic acid, 6 on oral bisphosphonates and 1 on denosumab. The mean difference in bone mineral density (BMD) was 5% at the lumbar spine and 4% at the total hip, at 12 months, favoring zoledronic acid compared to control. The certainty of the evidence was low for lumbar spine and moderate for total hip BMD. Similarly, the mean difference was 3% at the lumbar spine and 2% at the total hip, favoring oral bisphosphonates with moderate certainty. The mean difference was 6% at the lumbar spine, and 4% at the total hip BMD favoring denosumab compared to placebo. In addition, zoledronic acid resulted in a mean difference in bone turnover marker levels of -35-41%, and the relarive risk for morphometric vertebral fractures was 0.7 [0.3-1.4], compared to control. Denosumab reduced fracture incidence by 50% compared to placebo. CONCLUSION: Evidence suggests a protective effect of antiresorptive drugs on BMD and bone turnover markers in postmenopausal women with non-metastatic breast cancer on AI. However, data on fracture risk reduction remains unclear.

Treatment of Hypercalcemia of Malignancy.

The treatment of hypercalcemia of malignancy (HCM) consists of enhancing renal calcium excretion, mostly through hydration with isotonic fluids and the use of antiresorptive therapies. Intravenous zoledronic acid is currently the first-line treatment. Subcutaneous denosumab is used for bisphosphonate-refractory hypercalcemia and in patients with renal failure. There is no evidence that bisphosphonates prevent the occurrence of HCM. Conversely, denosumab, compared with zoledronic acid, is associated with a lower risk of HCM, both first episode and recurrence, in patients with breast cancer and multiple myeloma.

Bone Health Following Bariatric Surgery: An Update.

Obesity rates are increasing rapidly, and bariatric surgery is currently the most effective tool for weight loss. Recently, bariatric surgery induced bone loss has gained attention. Such detrimental effect on bone is multifactorial and causes may include nutrient deficiencies, gut and gonadal hormonal changes, mechanical unloading, loss of lean mass, increased bone marrow fat, and increased risk of fall. This review describes the available evidence on bone loss and fracture risk following bariatric surgery and summarizes the guidelines on the topic. Increased bone resorption starts early postsurgery, and bone markers peak at 1-2 yr. Across studies, the drop in areal bone mineral density is inconsistent at the lumbar spine, while a 2%-5% drop at 6 mo and a 6%-10.5% at 9-12 mo are observed at the total hip. Conversely, studies using quantitative CT showed a 6%-7% decrease in volumetric bone mineral density at the lumbar spine at 6-12 mo postsurgery. These studies also report significant bone loss at the radius and tibia, in addition to alteration in bone microarchitecture. Fracture risk increases 2 yr after surgery, more so following malabsorptive procedures. Fractures were reported at axial, weight bearing sites and at appendicular sites. The available evidence is very heterogeneous, and mostly derived from studies on Roux-en-y gastric bypass in premenopausal women. Data on restrictive procedures is scarce. Our findings suggest that the early postoperative phase represents the "golden window" to intervene and promote bone health. More research is needed to determine the effect of different bariatric procedures on bone, to identify optimal interventions to prevent bone loss and to characterize high risk individuals who should be targeted.

Vitamin D supplementation in obesity and during weight loss: A review of randomized controlled trials.

Vitamin D deficiency is common in obese individuals and during weight loss. The recommended vitamin D doses in this specific population are higher than for healthy adults. We reviewed vitamin D supplementation trials in obesity, and during medical or surgical weight loss, and report the effects on 25-hydroxyvitamin D [25(OH)D] concentrations and other relevant outcomes. We conducted a systematic search in PubMed, Medline, Embase and the Cochrane library for relevant randomized controlled trials (RCTs) of oral vitamin D supplementation for at least 3 months in obese individuals without weight loss (OB), and those on medical weight loss (MWL) (2010-2018), and following bariatric surgery (Bar S) (without time restriction). Two reviewers screened the identified citations in duplicate and independently and performed full text screening. One reviewer completed data extraction. We identified 13 RCTs in OB, 6 in MWL and 7 in Bar S. Mean baseline 25(OH)D concentrations ranged between 7 and 27 ng/ml in OB, 15-29 ng/ml in MWL and 15-24 ng/ml in Bar S. In OB (Total N 2036 participants), vitamin D doses of 1600-4000 IU/d increased mean 25(OH)D concentrations to ≥30 ng/ml. Based on three trials during MWL (Total N 359 participants), vitamin D doses of 1200-4600 IU/d for 12 months increased 25(OH)D concentration to ≥30 ng/ml. In Bar S (Total N 615 participants), doses ≥2000 IU/d were needed to reach 30 ng/ml. The change in 25(OH)D concentration was inversely proportional to the administered dose, and to BMI and baseline level with doses of 600-3000 IU/day. With these doses, the change in 25(OH)D concentration [Δ25(OH)D] per 100 IU/d was 0.5-1.2 ng/ml. Three trials assessed bone mineral density as a primary outcome, but only one of them showed a protective effect of vitamin D against bone loss at all sites post-Bar S. There was no effect of vitamin D on weight loss. Data on extra-skeletal parameters, namely glycemic and vascular indices were mostly identified in OB, and findings were inconsistent. In conclusion, Vitamin D doses ≥1600-2000 IU/d may be needed to reach a 25(OH)D concentration of 30 ng/ml in obese individuals and following bariatric surgery. The optimal concentration in this population is unknown, and whether the above doses protect against weight loss induced bone loss and fractures still needs to be confirmed. There is no clear evidence for a beneficial effect of vitamin D supplementation on cardio-metabolic parameters in obese individuals, and data on such parameters with weight loss are very scarce. Well-designed long term RCTs assessing the effect of vitamin D supplementation during weight loss on patient important outcomes are needed.

Vitamin D Metabolism in Bariatric Surgery.

Hypovitaminosis D is common in obese patients and persists after roux-en-Y gastric bypass and sleeve gastrectomy. Several societies recommend screening for vitamin D deficiency before bariatric surgery, and replacement doses of 3000 IU/d and up to 50,000 IU 1 to 3 times per week, in case of deficiency, with periodic monitoring. These regimens are mostly based on expert opinion. Large trials are needed to assess the vitamin D dose response, by type of bariatric surgery, and evaluate the effect on surrogate markers of skeletal outcomes. Such data are essential to derive desirable vitamin D levels in this population.

Guidelines on vitamin D replacement in bariatric surgery: Identification and systematic appraisal.

INTRODUCTION: Bariatric surgery is the most effective therapeutic option to reduce weight in morbidly obese individuals, but it results in a number of mineral and vitamin deficiencies. Clinical Practice Guidelines (CPGs) attempt to balance those benefits and harms to provide guidance to physicians and patients. OBJECTIVES: We compare and evaluate the quality of the evidence and of the development process of current CPGs that provide recommendations on vitamin D replacement in patients undergoing bariatric surgery, using a validated tool. METHODS: We searched 4 databases, with no time restriction, to identify relevant and current CPGs. Two reviewers assessed eligibility and abstracted data, in duplicate. They evaluated the quality of CPGs development process using the Appraisal of Guidelines, Research, and Evaluation II (AGREE II) tool that consists of 6 domains. A content expert verified those assessments. RESULTS: We identified 3 eligible CPGs: (1) the Endocrine Society (ES) guidelines (2010); (2) the American Association of Clinical Endocrinologists (AACE), The Obesity Society (TOS), and the American Society for Metabolic & Bariatric Surgery (ASMBS) guidelines (update 2013); and (3) the Interdisciplinary European (IE) guidelines on Metabolic and Bariatric Surgery (latest update 2014). The ES and the AACE/TOS/ASMBS guidelines recommended high doses of vitamin D, varying from 3000IU daily to 50,000IU 1-3 times weekly. Vitamin D doses were not mentioned in the IE guidelines. The recommendations were based on a low quality of evidence, if any, or limited to a single high quality trial, for some outcomes. In terms of quality, only the IE guidelines described their search methodology but none of the CPGs provided details on evidence selection and appraisal. None of the three CPGs rigorously assessed the preferences of the target population, resource implications, and the applicability of these guidelines. According to the AGREE II tool, we rated the ES guidelines as average in quality, and the other two as low in quality. CONCLUSION: Current CPGs recommendations on vitamin D supplementation in bariatric surgery differ between societies. They do not fulfill criteria for optimal guideline development, in part possibly due to limited resources, and are based on expert opinion. Thus, the pressing need for high quality randomized trials to inform CPGs, to be developed based on recommended standards.

Hypovitaminosis D in bariatric surgery: A systematic review of observational studies.

BACKGROUND: Obesity is a public health problem that carries global and substantial social and economic burden. Relative to non-surgical interventions, bariatric surgery has the most substantial and lasting impact on weight loss. However, it leads to a number of nutritional deficiencies requiring long term supplementation. OBJECTIVES: The aims of this paper are to review 25-hydroxyvitamin D [25(OH)D] status pre and post bariatric surgery, describe the dose response of vitamin D supplementation, and assess the effect of the surgical procedure on 25(OH)D level following supplementation. METHODS: We searched Medline, PubMed, the Cochrane Library and EMBASE, for relevant observational studies published in English, from 2000 to April 2015. The identified references were reviewed, in duplicate and independently, by two reviewers. RESULTS: We identified 51 eligible observational studies assessing 25(OH)D status pre and/or post bariatric surgery. Mean pre-surgery 25(OH)D level was below 30ng/ml in 29 studies, and 17 of these studies showed mean 25(OH)D levels ≤20ng/ml. Mean 25(OH)D levels remained below 30ng/ml following bariatric surgery, despite various vitamin D replacement regimens, with only few exceptions. The increase in post-operative 25(OH)D levels tended to parallel increments in vitamin D supplementation dose but varied widely across studies. An increase in 25(OH)D level by 9-13ng/ml was achieved when vitamin D deficiency was corrected using vitamin D replacement doses of 1100-7100IU/day, in addition to the usual maintenance equivalent daily dose of 400-2000IU (total equivalent daily dose 1500-9100IU). There was no difference in mean 25(OH)D level following supplementation between malabsorptive/combination procedures and restrictive procedures. CONCLUSION: Hypovitaminosisis D persists in obese patients undergoing bariatric surgery, despite various vitamin D supplementation regimens. Further research is needed to determine the optimal vitamin D dose to reach desirable 25(OH)D levels in this population, and to demonstrate whether this dose varies according to the surgical procedure.