Bone Metabolism in Adolescents Undergoing Bariatric Surgery

 描述(申请人提供)：肥胖已经达到流行的比例，是儿童和成人骨折的危险因素，尽管DXA测量的面积骨密度(BMD)更高。Roux-en-Y胃分流术(RYGB)和垂直袖状胃切除术(VSG)是越来越多的青少年使用的减肥手术。然而，对成年人的研究表明，加速的骨丢失可能是减肥手术的主要代谢并发症。这在青春期尤其值得关注，青春期是骨量最大的时期，达到骨量峰值，这是未来骨折风险的关键决定因素。尽管肥胖青少年的减肥手术变得越来越普遍，但对于常用减肥手术对青少年骨骼的影响，仍存在重大的知识差距。值得注意的是，在肥胖和减肥后使用DXA容易出现人为误差，可能不能反映骨强度的真实变化。相比之下，定量计算机断层扫描(QCT)和高分辨率外周QCT(HR-pQCT)避免了DXA的许多局限性，并可能提供对结构变化的关键洞察，而微有限元分析(µFEA)提供非侵入性强度估计。这些方法还没有被用来描述接受减肥手术的青少年的骨骼变化。最近的发展揭示了骨脂连接和骨髓脂肪组织(MAT)在骨质疏松发病机制中的潜在影响。然而，在青少年中，减肥手术对MAT(使用磁共振波谱(1H-MRS)活体测量)的影响尚未被研究。最后，了解RYGB和VSG后影响骨代谢的机制可以为未来的治疗提供参考，这在青少年中是缺乏的。我们的总体目标是综合评估接受RYGB和VSG治疗的病态肥胖青少年与匹配的非手术肥胖对照组(目标1)在两年内的骨骼健康状况，并调查导致减肥手术后骨代谢有害变化的机制(目标2)。用DXA和定量CT(QCT)评估脊柱和髋部的骨密度，并在RYGB和VSG治疗前和治疗后2年用DXA评估全身骨密度，并与匹配的非手术肥胖对照组比较。我们将评估骨转换的生化标记物和桡骨和胫骨的骨微结构变化(使用HRpQCT)，以确定骨重建/建模和微结构的变化如何影响骨，以及通过评估强度估计的变化(使用µFEA)这些变化对骨折风险的影响。骨髓脂肪将使用1H-MRS进行评估。最后，我们将评估骨骼、身体成分和激素之间的复杂相互作用，这些激素会随着RYGB和VSG(胰岛素、Ghrelin、多肽YY、雌激素)的变化而变化，并可能直接或通过激素(如硬化素和Pref-1)影响骨骼。我们已经为这项提议召集了具有互补实力的调查人员。

 DESCRIPTION (provided by applicant): Obesity has reached epidemic proportions and is a risk factor for fractures in both children and adults, despite higher DXA measures of areal bone mineral density (BMD). Roux-en-Y gastric bypass (RYGB) and vertical sleeve gastrectomy (VSG) are bariatric procedures that are increasingly used in adolescents. However, studies in adults suggest that accelerated bone loss may be a major metabolic complication of bariatric surgery. This is of particular concern during adolescence, a time of maximal bone accrual towards attainment of peak bone mass, a key determinant of future fracture risk. Although bariatric surgery in obese adolescents is becoming increasingly common, there is a major knowledge gap regarding consequences on bone in adolescents with commonly used bariatric procedures. Of note, the use of DXA in obesity and following weight loss is prone to artifactual inaccuracies and may not reflect true changes in bone strength. In contrast, quantitative computed tomography (QCT) and high-resolution peripheral QCT (HR-pQCT) avoid many limitations of DXA, and may yield critical insight about structural changes, and microfinite element analysis (µFEA) provides non-invasive strength estimates. These methods have not been utilized to characterize bone changes in adolescents undergoing bariatric surgery. Recent developments have brought to light the bone-fat connection and the potential impact of marrow adipose tissue (MAT) in the pathogenesis of osteoporosis. However, the impact of bariatric surgery on MAT (measured in vivo using magnetic resonance spectroscopy (1H-MRS)) has not been studied in adolescents. Finally, an understanding of mechanisms that impact bone metabolism after RYGB and VSG could inform future therapies, and is lacking in adolescents. Our overall goal is to comprehensively evaluate skeletal health over 2 years in morbidly obese adolescents undergoing RYGB and VSG compared with matched non-surgical obese controls (Aim 1), and investigate mechanisms that contribute to deleterious changes in bone metabolism following bariatric surgery (Aim 2). Bone density will be assessed at the spine and hip by DXA and quantitative CT (QCT), and the whole body by DXA, before and for 2 years after RYGB and VSG, compared to matched non-surgical obese controls. We will evaluate biochemical markers of bone turnover and changes in bone microarchitecture at the radius and tibia (using HRpQCT) to ascertain how alterations in bone re/modeling and microarchitecture impact bone, and the implication of these changes for fracture risk by assessing changes in strength estimates (using µFEA). Marrow fat will be assessed using 1H-MRS. Finally, we will evaluate complex interactions between bone, body composition and hormones that change with RYGB and VSG (insulin, ghrelin, peptide YY, estrogen) and may affect bone directly or via hormones such as sclerostin and Pref-1. We have assembled investigators with complimentary strengths for the proposal.