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，因为骨骼在这几年迅速积累，占成人峰值骨量（PBM）的一半，这是以后生活中骨骼脆弱性的有力预测指标。这一时期的钙摄入对足够的骨矿化至关重要；如果低，它可能导致低骨量和骨折的风险增加。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一个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由产生短链脂肪酸的肠道细菌发酵，可以促进矿物质的吸收，减少骨吸收。对大鼠的研究表明，与其他纤维相比，SCF是骨量最大、抗骨折能力最强的纤维。少数人体研究表明，青少年补充SCF会导致钙吸收的最大增加，但不知道这是否转化为骨量的增加，特别是在青春期的生长高峰期。因此，本提案的主要目的是确定与安慰剂相比，补充1年SCF对生长中的青少年骨代谢的影响。在该研究中，将对236名11-14岁的健康青少年进行随机双盲安慰剂对照临床试验，平均随机分配到四个干预组之一：SCF （12 g/d SCF + 600 mg/d元素钙）、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）；每天两次。骨量将在6个月和12个月时进行基线评估，骨相关生物标志物和粪便微生物组将在基线和12个月时进行评估。评估访问将在佛罗里达国际大学斯坦普尔公共卫生学院临床研究中心进行。我们还将在3个月和9个月时进行短期家访，收集未使用的补品，并提供更多的补品。将在所有访问中评估依从性，并使用研究移动应用程序进行实时评估。如果在饮食中补充SCF会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，与增加乳制品消费相比，用SCF强化不同的食物基质或补充剂可能是一种具有成本效益的骨骼健康干预措施，尤其是在青少年中。鉴于骨质疏松风险因素的前兆始于童年/青春期，并一直延续到成年期，在这些阶段进行干预，作为预防以后生活中骨质疏松性骨折的手段，具有巨大的潜力，并将其经济影响降到最低。

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.