Farr Joshua N, Dimitri Paul
Robert and Arlene Kogod Center on Aging and Endocrine Research Unit, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN, 55905, USA.
The Academic Unit of Child Health, Department of Paediatric Endocrinology, Sheffield Children's NHS Foundation Trust, University of Sheffield, Western Bank, Sheffield, S10 2TH, UK.
Calcif Tissue Int. 2017 May;100(5):500-513. doi: 10.1007/s00223-016-0218-3. Epub 2016 Dec 24.
A complex interplay of genetic, environmental, hormonal, and behavioral factors affect skeletal development, several of which are associated with childhood fractures. Given the rise in obesity worldwide, it is of particular concern that excess fat accumulation during childhood appears to be a risk factor for fractures. Plausible explanations for this higher fracture risk include a greater propensity for falls, greater force generation upon fall impact, unhealthy lifestyle habits, and excessive adipose tissue that may have direct or indirect detrimental effects on skeletal development. To date, there remains little resolution or agreement about the impact of obesity and adiposity on skeletal development as well as the mechanisms underpinning these changes. Limitations of imaging modalities, short duration of follow-up in longitudinal studies, and differences among cohorts examined may all contribute to conflicting results. Nonetheless, a linear relationship between increasing adiposity and skeletal development seems unlikely. Fat mass may confer advantages to the developing cortical and trabecular bone compartments, provided that gains in fat mass are not excessive. However, when fat mass accumulation reaches excessive levels, unfavorable metabolic changes may impede skeletal development. Mechanisms underpinning these changes may relate to changes in the hormonal milieu, with adipokines potentially playing a central role, but again findings have been confounding. Changes in the relationship between fat and bone also appear to be age and sex dependent. Clearly, more work is needed to better understand the controversial impact of fat and obesity on skeletal development and fracture risk during childhood.
遗传、环境、激素和行为因素之间复杂的相互作用会影响骨骼发育,其中一些因素与儿童骨折有关。鉴于全球肥胖率的上升,尤其令人担忧的是,儿童期脂肪过度积累似乎是骨折的一个风险因素。这种较高骨折风险的合理原因包括跌倒倾向更大、跌倒撞击时产生的力量更大、不健康的生活方式习惯以及过多的脂肪组织可能对骨骼发育产生直接或间接的不利影响。迄今为止,关于肥胖和肥胖对骨骼发育的影响以及这些变化背后的机制,仍几乎没有定论或共识。成像方式的局限性、纵向研究随访时间短以及所研究队列之间的差异,都可能导致结果相互矛盾。尽管如此,肥胖增加与骨骼发育之间似乎不太可能存在线性关系。脂肪量可能会给正在发育的皮质骨和小梁骨带来好处,前提是脂肪量的增加不过度。然而,当脂肪量积累达到过高水平时,不利的代谢变化可能会阻碍骨骼发育。这些变化背后的机制可能与激素环境的变化有关,脂肪因子可能在其中发挥核心作用,但同样,研究结果也一直令人困惑。脂肪与骨骼关系的变化似乎也与年龄和性别有关。显然,需要开展更多工作,以更好地了解脂肪和肥胖对儿童骨骼发育和骨折风险的争议性影响。