Bone Metabolism in Adolescents Undergoing Bariatric Surgery

 描述（由申请人提供）：尽管DXA测量的骨密度（BMD）较高，但肥胖已达到流行比例，是儿童和成人骨折的危险因素。Roux-en-Y胃旁路术（RYGB）和垂直袖状胃切除术（VSG）是越来越多地用于青少年的减肥手术。然而，成人研究表明，加速骨丢失可能是减肥手术的主要代谢并发症。这在青春期尤其令人担忧，青春期是达到峰值骨量的最大骨增量时期，是未来骨折风险的关键决定因素。虽然肥胖青少年的减肥手术越来越普遍，但关于常用减肥手术对青少年骨骼的影响存在重大知识缺口。值得注意的是，DXA在肥胖和体重减轻后的使用容易出现人为的不准确性，可能无法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，并可能产生关于结构变化的关键见解，而微观有限元分析（µFEA）提供了无创强度估计。这些方法尚未用于描述接受减肥手术的青少年的骨变化。最近的发展揭示了骨脂肪连接和骨髓脂肪组织（MAT）在骨质疏松症发病机制中的潜在影响。然而，减肥手术对MAT（使用磁共振波谱（1H-MRS）在体内测量）的影响尚未在青少年中研究。最后，对RYGB和VSG后影响骨代谢的机制的理解可以为未来的治疗提供信息，而这在青少年中是缺乏的。我们的总体目标是综合评价接受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在2年内的骨骼健康状况（目的1），并研究导致减肥手术后骨代谢有害变化的机制（目的2）。在RYGB和VSG之前和之后2年，通过DXA和定量CT（QCT）评估脊柱和髋关节的骨密度，并通过DXA评估全身骨密度，与匹配的非手术肥胖对照组进行比较。我们将评估骨转换的生化标志物以及桡骨和胫骨骨微结构的变化（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值的变化（使用µFEA）确定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、身体成分和激素之间的复杂相互作用，这些激素随RYGB和VSG（胰岛素、生长激素释放肽、肽YY、雌激素）而变化，并可能直接或通过激素（如硬化素和Pref-1）影响骨。我们已经召集了具有互补优势的调查人员来支持这项建议。

 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.