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Bone Marrow Fat Changes After Gastric Bypass Surgery Are Associated With Loss of Bone Mass.

ABSTRACT: Bone marrow fat is a unique fat depot that may regulate bone metabolism. Marrow fat is increased in states of low bone mass, severe underweight, and diabetes. However, longitudinal effects of weight loss and improved glucose homeostasis on marrow fat are unclear, as is the relationship between marrow fat and bone mineral density (BMD) changes. We hypothesized that after Roux-en-Y gastric bypass (RYGB) surgery, marrow fat changes are associated with BMD loss. We enrolled 30 obese women, stratified by diabetes status. Before and 6 months after RYGB, we measured BMD by dual-energy X-ray absorptiometry (DXA) and quantitative computed tomography (QCT) and vertebral marrow fat content by magnetic resonance spectroscopy. At baseline, those with higher marrow fat had lower BMD. Postoperatively, total body fat declined dramatically in all participants. Effects of RYGB on marrow fat differed by diabetes status (p?=?0.03). Nondiabetic women showed no significant mean change in marrow fat (+1.8%, 95% confidence interval [CI] -1.8% to +5.4%, p?=?0.29), although those who lost more total body fat were more likely to have marrow fat increases (r?=?-0.70, p?=?0.01). In contrast, diabetic women demonstrated a mean marrow fat change of -6.5% (95% CI -13.1% to 0%, p?=?0.05). Overall, those with greater improvements in hemoglobin A1c had decreases in marrow fat (r?=?0.50, p?=?0.01). Increases in IGF-1, a potential mediator of the marrow fat-bone relationship, were associated with marrow fat declines (r?=?-0.40, p?=?0.05). Spinal volumetric BMD decreased by 6.4%?±?5.9% (p?

SUBMITTER: Kim TY

PROVIDER: S-EPMC5685913 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

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Bone Marrow Fat Changes After Gastric Bypass Surgery Are Associated With Loss of Bone Mass.

Kim Tiffany Y TY Schwartz Ann V AV Li Xiaojuan X Xu Kaipin K Black Dennis M DM Petrenko Dimitry M DM Stewart Lygia L Rogers Stanley J SJ Posselt Andrew M AM Carter Jonathan T JT Shoback Dolores M DM Schafer Anne L AL

Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 20170809 11

Bone marrow fat is a unique fat depot that may regulate bone metabolism. Marrow fat is increased in states of low bone mass, severe underweight, and diabetes. However, longitudinal effects of weight loss and improved glucose homeostasis on marrow fat are unclear, as is the relationship between marrow fat and bone mineral density (BMD) changes. We hypothesized that after Roux-en-Y gastric bypass (RYGB) surgery, marrow fat changes are associated with BMD loss. We enrolled 30 obese women, stratifie ...[more]

PMID: 28791737

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Project description:Roux-en Y gastric bypass (RYGB) surgery is an effective treatment for obesity; however, it may negatively impact skeletal health by increasing fracture risk. This increase may be the result not only of decreased bone mineral density but also of changes in bone microstructure, for example, increased cortical porosity. Increased tibial and radial cortical porosity of patients undergoing RYGB surgery has been observed as early as 6 months postoperatively; however, local microstructural changes and associated biological mechanisms driving this increase remain unclear. To provide insight, we studied the spatial distribution of cortical porosity in 42 women and men (aged 46 ± 12 years) after RYGB surgery. Distal tibias and radii were evaluated with high-resolution peripheral quantitative computed tomography (HR-pQCT) preoperatively and at 12 months postoperatively. Laminar analysis was used to determine cortical pore number and size within the endosteal, midcortical, and periosteal layers of the cortex. Paired t tests were used to compare baseline versus follow-up porosity parameters in each layer. Mixed models were used to compare longitudinal changes in laminar analysis outcomes between layers. We found that the midcortical (0.927 ± 0.607 mm-2 to 1.069 ± 0.654 mm-2 , p = 0.004; 0.439 ± 0.293 mm-2 to 0.509 ± 0.343 mm-2 , p = 0.03) and periosteal (0.642 ± 0.412 mm-2 to 0.843 ± 0.452 mm-2 , p < 0.0001; 0.171 ± 0.101 mm-2 to 0.230 ± 0.160 mm-2 , p = 0.003) layers underwent the greatest increases in porosity over the 12-month period at the distal tibia and radius, respectively. The endosteal layer, which had the greatest porosity at baseline, did not undergo significant porosity increase over the same period (1.234 ± 0.402 mm-2 to 1.259 ± 0.413 mm-2 , p = 0.49; 0.584 ± 0.290 mm-2 to 0.620 ± 0.299 mm-2 , p = 0.35) at the distal tibia and radius, respectively. An alternative baseline-mapping approach for endosteal boundary definition confirmed that cortical bone loss was not primarily endosteal. These findings indicate that increases in cortical porosity happen in regions distant from the endosteal surface, suggesting that the underlying mechanism driving the increase in cortical porosity is not merely endosteal trabecularization. © 2022 American Society for Bone and Mineral Research (ASBMR).

Project description:ContextBariatric surgery is increasingly popular but may lead to metabolic bone disease.ObjectiveThe objective was to determine the rate of bone loss in the 24 months after Roux-en-Y gastric bypass.Design and settingThis was a prospective cohort study conducted at an academic medical center.ParticipantsThe participants were adults with severe obesity, including 30 adults undergoing gastric bypass and 20 nonsurgical controls.OutcomesWe 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.ResultsWeight 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.ConclusionsSubstantial 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.

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.

Project description:Roux-en-Y gastric bypass (RYGB) surgery is a highly effective treatment for obesity but negatively affects the skeleton. Studies of skeletal effects have generally examined areal bone mineral density (BMD) by dual-energy X-ray absorptiometry (DXA), but DXA may be inaccurate in the setting of marked weight loss. Further, as a result of modestly sized samples of mostly premenopausal women and very few men, effects of RYGB by sex and menopausal status are unknown. We prospectively studied the effects of RYGB on skeletal health, including axial and appendicular volumetric BMD and appendicular bone microarchitecture and estimated strength. Obese adults (N?=?48; 27 premenopausal and 11 postmenopausal women, 10 men) with mean?±?SD body mass index (BMI) 44?±?7?kg/m2 were assessed before and 6 and 12 months after RYGB. Participants underwent spine and hip DXA, spine QCT, radius and tibia HR-pQCT, and laboratory evaluation. Mean 12-month weight loss was 37?kg (30% of preoperative weight). Overall median 12-month increase in serum collagen type I C-telopeptide (CTx) was 278% (p < 0.0001), with greater increases in postmenopausal than premenopausal women (p?=?0.049). Femoral neck BMD by DXA decreased by mean 5.0% and 8.0% over 6 and 12 months (p < 0.0001). Spinal BMD by QCT decreased by mean 6.6% and 8.1% (p < 0.0001); declines were larger among postmenopausal than premenopausal women (11.6% versus 6.0% at 12 months, p?=?0.02). Radial and tibial BMD and estimated strength by HR-pQCT declined. At the tibia, detrimental changes in trabecular microarchitecture were apparent at 6 and 12 months. Cortical porosity increased at the radius and tibia, with more dramatic 12-month increases among postmenopausal than premenopausal women or men at the tibia (51.4% versus 18.3% versus 3.0%, p < 0.01 between groups). In conclusion, detrimental effects of RYGB on axial and appendicular bone mass and microarchitecture are detectable as early as 6 months postoperatively. Postmenopausal women are at highest risk for skeletal consequences and may warrant targeted screening or interventions. © 2017 American Society for Bone and Mineral Research.

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Bone Marrow Fat Changes After Gastric Bypass Surgery Are Associated With Loss of Bone Mass.

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Bone Marrow Fat Changes After Gastric Bypass Surgery Are Associated With Loss of Bone Mass.

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