Dataset Information

Two-year changes in bone density after Roux-en-Y gastric bypass surgery.

ABSTRACT: Bariatric surgery is increasingly popular but may lead to metabolic bone disease.The objective was to determine the rate of bone loss in the 24 months after Roux-en-Y gastric bypass.This was a prospective cohort study conducted at an academic medical center.The participants were adults with severe obesity, including 30 adults undergoing gastric bypass and 20 nonsurgical controls.We measured bone mineral density (BMD) at the lumbar spine and proximal femur by quantitative computed tomography (QCT) and dual-energy x-ray absorptiometry at 0, 12, and 24 months. BMD and bone microarchitecture were also assessed by high-resolution peripheral QCT, and estimated bone strength was calculated using microfinite element analysis.Weight loss plateaued 6 months after gastric bypass but remained greater than controls at 24 months (-37 ± 3 vs -5 ± 3 kg [ mean ± SEM]; P < .001). At 24 months, BMD was 5-7% lower at the spine and 6-10% lower at the hip in subjects who underwent gastric bypass compared with nonsurgical controls, as assessed by QCT and dual-energy x-ray absorptiometry (P < .001 for all). Despite significant bone loss, average T-scores remained in the normal range 24 months after gastric bypass. Cortical and trabecular BMD and microarchitecture at the distal radius and tibia deteriorated in the gastric bypass group throughout the 24 months, such that estimated bone strength was 9% lower than controls. The decline in BMD persisted beyond the first year, with rates of bone loss exceeding controls throughout the second year at all skeletal sites. Mean serum calcium, 25(OH)-vitamin D, and PTH were maintained within the normal range in both groups.Substantial bone loss occurs throughout the 24 months after gastric bypass despite weight stability in the second year. Although the benefits of gastric bypass surgery are well established, the potential for adverse effects on skeletal integrity remains an important concern.

SUBMITTER: Yu EW

PROVIDER: S-EPMC4399296 | biostudies-literature | 2015 Apr

REPOSITORIES: biostudies-literature

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Two-year changes in bone density after Roux-en-Y gastric bypass surgery.

Yu Elaine W EW Bouxsein Mary L ML Putman Melissa S MS Monis Elizabeth L EL Roy Adam E AE Pratt Janey S A JS Butsch W Scott WS Finkelstein Joel S JS

The Journal of clinical endocrinology and metabolism 20150203 4

<h4>Context</h4>Bariatric surgery is increasingly popular but may lead to metabolic bone disease.<h4>Objective</h4>The objective was to determine the rate of bone loss in the 24 months after Roux-en-Y gastric bypass.<h4>Design and setting</h4>This was a prospective cohort study conducted at an academic medical center.<h4>Participants</h4>The participants were adults with severe obesity, including 30 adults undergoing gastric bypass and 20 nonsurgical controls.<h4>Outcomes</h4>We measured bone mi ...[more]

PMID: 25646793

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Project description:BackgroundThe mechanisms of weight loss and metabolic improvements following bariatric surgery in skeletal muscle are not well known; however, epigenetic modifications are likely to contribute. The aim of our study was to investigate skeletal muscle DNA methylation after weight loss induced by Roux-en-Y gastric bypass (RYGB) surgery. Muscle biopsies were obtained basally from seven insulin-resistant obese (BMI > 40 kg/m2) female subjects (45.1 ± 3.6 years) pre- and 3-month post-surgery with euglycemic hyperinsulinemic clamps to assess insulin sensitivity. Four lean (BMI < 25 kg/m2) females (38.5 ± 5.8 years) served as controls. We performed reduced representation bisulfite sequencing next generation methylation on DNA isolated from the vastus lateralis muscle biopsies.ResultsGlobal methylation was significantly higher in the pre- (32.97 ± 0.02%) and post-surgery (33.31 ± 0.02%) compared to the lean (30.46 ± 0.02%), P < 0.05. MethylSig analysis identified 117 differentially methylated cytosines (DMCs) that were significantly altered in the post- versus pre-surgery (Benjamini-Hochberg q < 0.05). In addition, 2978 DMCs were significantly altered in the pre-surgery obese versus the lean controls (Benjamini-Hochberg q < 0.05). For the post-surgery obese versus the lean controls, 2885 DMCs were altered (Benjamini-Hochberg q < 0.05). Seven post-surgery obese DMCs were normalized to levels similar to those observed in lean controls. Of these, 5 were within intergenic regions (chr11.68,968,018, chr16.73,100,688, chr5.174,115,531, chr5.1,831,958 and chr9.98,547,011) and the remaining two DMCs chr17.45,330,989 and chr14.105,353,824 were within in the integrin beta 3 (ITGB3) promoter and KIAA0284 exon, respectively. ITGB3 methylation was significantly decreased in the post-surgery (0.5 ± 0.5%) and lean controls (0 ± 0%) versus pre-surgery (13.6 ± 2.7%, P < 0.05). This decreased methylation post-surgery was associated with an increase in ITGB3 gene expression (fold change + 1.52, P = 0.0087). In addition, we showed that ITGB3 promoter methylation in vitro significantly suppressed transcriptional activity (P < 0.05). Transcription factor binding analysis for ITGB3 chr17.45,330,989 identified three putative transcription factor binding motifs; PAX-5, p53 and AP-2alphaA.ConclusionsThese results demonstrate that weight loss after RYGB alters the epigenome through DNA methylation. In particular, this study highlights ITGB3 as a novel gene that may contribute to the metabolic improvements observed post-surgery. Future additional studies are warranted to address the exact mechanism of ITGB3 in skeletal muscle.

Dataset Information

Two-year changes in bone density after Roux-en-Y gastric bypass surgery.

Publications

Two-year changes in bone density after Roux-en-Y gastric bypass surgery.

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