Effect of Soluble Corn Fiber supplementation for 1 year on bone metabolism in adolescents (MetA-Bone Trial)

青春期对于优化未来的骨骼健康至关重要，因为骨骼在这些年中迅速积累，占成年峰值骨量（PBM）的一半，这是生命后期骨骼脆弱性的强有力预测因素。在此期间钙的摄入对于充分的骨矿化至关重要;如果低，可能导致低骨量和骨折风险增加。钙是美国青少年饮食中最缺乏的营养素，只有30%的人符合建议。在青春期最大化骨矿化的策略是增加钙的吸收，这可以通过补充不可消化的碳水化合物来实现，如可溶性玉米纤维（SCF）。SCF由肠道细菌发酵产生短链脂肪酸，可促进矿物质的吸收，降低骨吸收。对大鼠的研究表明，与其他纤维相比，SCF是导致最大骨量和抗骨折的纤维。在人类中的少数研究表明，补充SCF青少年导致钙吸收的最大增加，但尚不清楚这是否会转化为骨量的增加，特别是在青春期生长突增期间。因此，本提案的主要目的是确定与安慰剂相比，补充SCF 1年对生长期青少年骨代谢的影响。对于拟定的研究，将在236名11-14岁的健康青少年中进行一项随机双盲安慰剂对照临床试验，这些青少年平均随机分配至4个干预组之一：SCF（12 g/d），SCF +钙（12 g/d SCF + 600 mg/d元素钙）、安慰剂（0 g/d SCF或钙）和安慰剂+钙（0 g/d SCF + 600 mg/d元素钙）;均每天给药两次。将在6个月和12个月的基线时评估骨量，并将在基线和12个月时评估骨相关生物标志物和粪便微生物组。评估访视将在佛罗里达国际大学Stempel公共卫生学院的临床研究中心进行。我们还将在3个月和9个月进行短期家访，以收集未使用的补充剂并提供更多补充剂。将在所有访视时以及使用研究移动的应用程序在真实的时间内评价依从性。如果补充SCF饮食导致青春期骨量显著增加，这可能有助于实现PBM的遗传潜力，并以更强壮的骨骼开始成年生活。在人群水平上，用SCF强化不同的食物基质或补充剂可能比增加乳制品消费量更具有成本效益，特别是在青少年中。鉴于骨质疏松症风险因素的前因开始于儿童/青春期并持续到成年期，在这些阶段进行干预具有巨大的潜力，可作为预防以后生活中骨质疏松性骨折并最大限度地减少其经济影响的手段。

Adolescence is crucial for optimizing future bone health because bone accumulates rapidly during these years and accounts for up to half of adult peak bone mass (PBM), which is a strong predictor of bone fragility later in life. Calcium intake during this period is critical for adequate bone mineralization; if low, it could lead to low bone mass and increased risk of fractures. Calcium is the nutrient most deficient in the diets of US adolescents, with only 30% meeting the recommendation. A strategy to maximize bone mineralization in adolescence is to increase calcium absorption, which could be achieved by supplementation with non-digestible carbohydrates, such as soluble corn fiber (SCF). SCF is fermented by gut bacteria producing short-chain fatty acids, which improves absorption of minerals and could decrease bone resorption. Studies in rats show that SCF is the fiber that results in the greatest bone mass and resistance to fractures compared to other fibers. The few studies in humans show that supplementing adolescents with SCF results in the greatest increase in calcium absorption but it is not known if this translates into an increase in bone mass, particularly during the period of adolescence growth spurt. Therefore, the primary aim of this proposal is to determine the effects of SCF supplementation for 1 year on bone metabolism in growing adolescents compared to placebo. For the proposed study, a randomized double-blinded placebo controlled clinical trial will be conducted in 236 healthy adolescents aged 11-14 years, equally randomly assigned to one of four intervention groups: SCF (12 g/d), SCF + calcium (12 g/d of SCF + 600 mg/d of elemental calcium), placebo (0 g/d of SCF or of calcium), and placebo + calcium (0 g/d of SCF + 600 mg/d of elemental calcium); all administered twice a day. Bone mass will be assessed at baseline at 6 months and at 12 months and bone related biomarkers and fecal microbiome will be assessed at baseline and at 12 months. Assessment visits will be conducted in the Clinical Research Center of the Stempel School of Public Health at Florida International University. We will also have short home visits at 3 and 9 months to collect unused supplements and provide more supplements. Compliance will be evaluated at all visits and also in real time using a study mobile app. If supplementing diets with SCF lead to significantly higher bone mass in adolescence, this could help to achieve the genetic potential for PBM and to start adult life with stronger bones. Fortifying different food matrices or supplements with SCF may be a cost-effective intervention at the population level for bone health than increasing dairy products consumption, particularly in adolescents. Given that the antecedents to osteoporosis risk factors begin in childhood/adolescence and track into adulthood, intervening at these stages has tremendous potential as means for preventing osteoporotic fractures later in life and minimizing its economic impact.