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. 2022 Jan;154:116183. doi: 10.1016/j.bone.2021.116183. Epub 2021 Sep 29.
Neurofibromatosis type 1 (NF1) is associated with lower bone mass and increased risk of fracture. Children with NF1 display faltering growth from mid-childhood. However, to date tibia bone development in children with NF1 across childhood and the role of body size have not been explored. Therefore, we recruited 24 children with NF1 (12 girls, mean age 8.2 ± 1.1y) and 104 children without NF1 (52 girls, mean age 11 ± 1.7y). Tibia and fibula bone characteristics were assessed at 4% and 38% distal-proximal tibia length in all children at baseline using peripheral quantitative computed tomography (pQCT). Longitudinal scans were obtained in 21 children with NF1 (12 girls) over 3.4 ± 0.3y and 71 children without NF1 (34 girls) over 1.1 ± 0.1y, such that at follow-up mean age of both groups (NF1 10.9 ± 1.3y, controls 11.4 ± 1.4y) were similar. Effects of group (NF1/control) on bone outcomes as well as group-by-age interactions, indicating differences in rate of change in bone outcome bone outcomes were assessed via linear mixed effects models with adjustment for sex, age, pubertal status and in additional models with adjustment for height and weight Z-scores. Group (NF1/control)-by-age interactions indicated a slower rate of tibia and fibula bone mass accrual in children with NF1 at all measured sites. These associations were attenuated by 25-50% by adjustment for height and weight Z-scores. At the 4% site, deficits in bone mass at older ages were related to slower trabecular BMD accrual. At the 38% site, group-by-age interactions suggested that bone mass deficits resulted from poorer accrual of cortical CSA and to a lesser extent cortical BMD. Lower limb bone mass deficits evident in children with NF1 appear to be progressive and emerge in mid-childhood. In part, they are related to development of a similar pattern of deficits in longitudinal growth and body weight in NF1. Interventions promoting muscle development or physical activity may be partially effective in attenuating bone mass accrual deficits in this population.
神经纤维瘤病 1 型（NF1）与骨量减少和骨折风险增加有关。NF1 患儿从中年起生长缓慢。然而，迄今为止，NF1 患儿在整个儿童期的胫骨骨发育情况以及身体大小的作用尚未得到探索。因此，我们招募了 24 名 NF1 患儿（12 名女孩，平均年龄 8.2±1.1 岁）和 104 名无 NF1 患儿（52 名女孩，平均年龄 11±1.7 岁）。所有儿童在基线时均使用外周定量计算机断层扫描（pQCT）在胫骨远端近端 4%和 38%处评估胫骨和腓骨骨特征。在 21 名 NF1 患儿（12 名女孩）中进行了纵向扫描，随访时间为 3.4±0.3 年，在 71 名无 NF1 患儿（34 名女孩）中进行了 1.1±0.1 年的随访，因此两组的平均年龄（NF1 组 10.9±1.3 岁，对照组 11.4±1.4 岁）相似。通过线性混合效应模型评估组（NF1/对照）对骨结局的影响以及组-年龄相互作用，表明骨结局变化率的差异，通过线性混合效应模型进行评估，同时调整性别、年龄、青春期状态，并在额外的模型中调整身高和体重 Z 分数。组（NF1/对照）-年龄相互作用表明，在所有测量部位，NF1 患儿的胫骨和腓骨骨量积累速度较慢。通过调整身高和体重 Z 分数，这些关联减弱了 25-50%。在 4%的部位，年龄较大时的骨量不足与骨小梁 BMD 积累速度较慢有关。在 38%的部位，组-年龄相互作用表明，骨量不足是由于皮质 CSA 的积累较差以及皮质 BMD 的积累程度较低所致。NF1 患儿下肢骨量不足似乎呈进行性，从中年开始出现。在某种程度上，它们与 NF1 中纵向生长和体重的类似缺陷模式的发展有关。促进肌肉发育或体育活动的干预措施可能在一定程度上有效减轻该人群的骨量积累不足。
