Musculoskeletal Science and Sports Medicine Research Centre, Department of Life Sciences, Manchester Metropolitan University, Manchester, UK.
Institute for Infection and Immunity, Paediatric Infectious Diseases Research Group, St. George's University of London, UK; Previously at MRC Human Nutrition Research, Elsie Widdowson Laboratory, Cambridge, UK.
Bone. 2023 May;170:116657. doi: 10.1016/j.bone.2022.116657. Epub 2023 Jan 20.
Cystic fibrosis (CF) is a genetic condition primarily affecting the respiratory system, with the associated progressive lung damage and loss of function resulting in reduced lifespan. Bone health is also impaired in individuals with CF, leading to much higher fracture risk even in adolescence. However, the development of these deficits during growth and the relative contributions of puberty, body size and muscular loading remain somewhat unexplored. We therefore recruited 25 children with CF (10 girls, mean age 11.3 ± 2.9y) and 147 children without CF (75 girls, mean age 12.4 ± 2.6y). Bone characteristics were assessed using peripheral quantitative computed tomography (pQCT) at 4 % and 66 % distal-proximal tibia. Muscle cross-sectional area (CSA) and density (an indicator of muscle quality) were also assessed at the latter site. Tibial bone microstructure was assessed using high-resolution pQCT (HR-pQCT) at 8 % distal-proximal tibial length. In addition, peak jump power and hop force were measured using jumping mechanography. Group-by-age interactions and group differences in bone and muscle characteristics were examined using multiple linear regression, adjusted for age, sex and pubertal status and in additional models, height and muscle force. In initial models group-by-age interactions were evident for distal tibial total bone mineral content (BMC) and trabecular volumetric bone mineral density (vBMD), with a lower rate of age-related accrual evident in children with CF. In assessments of distal tibial microstructure, similar patterns were observed for trabecular number and thickness, and cortical CSA. In the tibial shaft, group-by-age interactions indicating slower growth in CF were evident for total BMC and cortical CSA, whilst age-independent deficits in CF were observed for several other variables. Peak jump power and hop force also exhibited similar interactions. Group-by-age interactions for bone were partially attenuated at the distal tibia and fully attenuated at the tibial shaft by adjustment for muscle force. These results suggest that bone and muscle deficits in children with CF develop throughout later childhood, independent of differences in pubertal stage and body size. These diverging growth patterns appear to be mediated by differences in muscle function, particularly for bone characteristics in the tibial shaft. Given the high fracture risk in this population from childhood onwards, development of interventions to improve bone health would be of substantial clinical value.
囊性纤维化（CF）是一种主要影响呼吸系统的遗传疾病，其相关的进行性肺损伤和功能丧失导致寿命缩短。CF 患者的骨骼健康也受到损害，导致即使在青春期骨折风险也高得多。然而，在生长过程中这些缺陷的发展以及青春期、体型和肌肉负荷的相对贡献仍在一定程度上尚未得到探索。因此，我们招募了 25 名 CF 患儿（10 名女孩，平均年龄 11.3 ± 2.9 岁）和 147 名非 CF 患儿（75 名女孩，平均年龄 12.4 ± 2.6 岁）。使用外周定量计算机断层扫描（pQCT）在 4%和 66%的远端-近端胫骨处评估骨骼特征。在后者部位还评估了肌肉横截面积（CSA）和密度（肌肉质量的指标）。使用高分辨率 pQCT（HR-pQCT）在 8%的远端-近端胫骨长度处评估胫骨骨微结构。此外，使用跳跃力学测量法测量峰值跳跃力和跳跃力。使用多元线性回归分析，调整年龄、性别和青春期状态，并在其他模型中调整身高和肌肉力量，检查骨骼和肌肉特征的组-年龄相互作用和组间差异。在初始模型中，CF 患儿的远端胫骨总骨矿物质含量（BMC）和小梁体积骨矿物质密度（vBMD）出现组-年龄相互作用，表明与年龄相关的积累速度较慢。在远端胫骨微结构评估中，观察到小梁数量和厚度以及皮质 CSA 的相似模式。在胫骨干中，CF 中出现了总 BMC 和皮质 CSA 生长较慢的组-年龄相互作用，而 CF 中观察到了几个其他变量的与年龄无关的缺陷。峰值跳跃力和跳跃力也表现出类似的相互作用。通过调整肌肉力量，在远端胫骨处，CF 患儿的骨骼和肌肉的组-年龄相互作用部分减弱，而在胫骨干处完全减弱。这些结果表明，CF 患儿的骨骼和肌肉缺陷在整个后期儿童期发展，与青春期阶段和体型的差异无关。这些发散的生长模式似乎是由肌肉功能的差异介导的，特别是在胫骨干的骨骼特征中。鉴于该人群从儿童期开始就有很高的骨折风险，因此开发改善骨骼健康的干预措施将具有重要的临床价值。
