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，因为骨骼在这些年里快速积累，占成年人峰值骨量(PBM)的一半，这是晚年骨骼脆性的有力预测因素。这一时期的钙摄入量对足够的骨矿化至关重要；如果钙摄入量过低，可能会导致骨量减少，增加骨折的风险。钙是美国青少年饮食中最缺乏的营养物质，只有30%的人符合推荐标准。在青春期最大限度地增加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，如可溶性玉米纤维(SCF)来实现。SCF是由产生短链脂肪酸的肠道细菌发酵的，短链脂肪酸可以促进矿物质的吸收，并可以减少骨吸收。对大鼠的研究表明，与其他纤维相比，SCF是一种能够产生最大骨量和抗骨折能力的纤维。在人体上的少数研究表明，补充干细胞因子的青少年钙吸收增加最多，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发期。因此，这项建议的主要目的是确定与安慰剂相比，补充SCF 1年对成长中青少年骨代谢的影响。在拟议的研究中，将在236名11-14岁的健康青少年中进行随机双盲安慰剂对照临床试验，随机分配到四个干预组之一：SCF(12g/d)、SCF+钙(12g/d+元素钙600 mg/d)、安慰剂(0g/d SCF或钙)和安慰剂+钙(0g/d SCF+600 mg/d元素钙)；均为每日两次。骨量将在基线6个月和12个月时进行评估，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的临床研究中心进行。我们还将在3个月和9个月时进行短期家访，收集未使用的补充剂，并提供更多补充剂。合规性将在所有访问中进行评估，并使用研究移动应用程序进行实时评估。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，并开始拥有更强壮的骨骼的成年生活。在人群水平上使用SCF强化不同的食物基质或补充剂可能是一种比增加乳制品消费更具成本效益的骨骼健康干预措施，特别是在青少年中。鉴于骨质疏松风险因素的前驱因素始于儿童/青春期，并一直持续到成年，在这些阶段进行干预具有巨大的潜力，可以作为预防晚年骨质疏松性骨折和将其经济影响降至最低的手段。

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.