Department of Endocrinology and Diabetes, Birmingham Women's and Children's NHS Foundation Trust, Birmingham, UK; Department of Paediatrics, Heartlands Hospital, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK.
Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, UK.
Bone. 2022 Jan;154:116248. doi: 10.1016/j.bone.2021.116248. Epub 2021 Oct 27.
Glucocorticoids are currently used to improve muscle strength and prolong ambulation in boys with DMD although the effect on bone health is still unclear. The aim of this study was to compare bone strength in healthy children and boys with DMD and investigate the interaction between diminished muscle function, loss of ambulation and high dose oral steroids, over a two year time frame. Fifty children were studied, 14 healthy boys (HB), 13 boys with DMD who remained ambulant (DMD-RA) and 23 boys with DMD who lost ambulation (DMD-LA). All boys with DMD had taken oral glucocorticoids. Peripheral quantitative computed tomography was used to measure bone geometry, density, strength and muscle mass of the non-dominant tibia and radius. Measurements were made at baseline, 12 and 24 months at the distal metaphysis and mid diaphysis sites. Differences between the three groups were evaluated using ANOVA and a repeated measures model. There were no significant differences in age between the groups: mean age was 9.4, 8.7 and 8.8 years for HB, DMD-RA and DMD-LA, respectively. There was no significant difference in steroid exposure between the DMD groups. However, boys who lost ambulation had significantly lower muscle function at baseline (North Star Ambulatory Assessment DMD-RA 23.6 vs. DMD-LA 18.8; p < 0.05). At baseline, healthy boys had significantly greater trabecular bone density at the distal radius /ulna (23%/27%) and distal tibia/fibula (30%/46%) than boys with DMD (p < 0.05). They also had significantly larger diaphyseal tibiae/fibulae (74%/36%) and radii/ulnae (49%/31%) with thicker corticies and consequently greater bone strength. In contrast, boys with DMD had greater cortical density (4%). Over time, there were small significant differences in the rate of change of both muscle and bone parameters between healthy boys and boys with DMD. For both ambulant and non-ambulant boys with DMD the greatest changes in cortical bone were evident at the tibia. After two years boys with DMD had on average, 63% less bone strength than healthy boys. However, the most strikingly significant difference was in trabecular bone density for boys who became non-ambulant. By 2 years non-ambulant DMD boys had 53% less trabecular bone density at distal tibia than their healthy age matched peers compared with boys who remained ambulant who had 27% less trabecular bone density. In conclusion, bone and muscle strength is reduced for all boys with DMD even while they remain ambulant. However, tibia trabecular bone density loss is significantly accelerated in DMD boys who lose independent ambulation compared to DMD boys who remain ambulant despite equivalent levels of corticosteroid exposure.
目前，糖皮质激素被用于改善 DMD 男孩的肌肉力量并延长其行走能力，尽管其对骨骼健康的影响仍不清楚。本研究的目的是比较健康儿童和 DMD 男孩的骨骼强度，并在两年的时间内研究肌肉功能下降、丧失行走能力和高剂量口服类固醇之间的相互作用。研究了 50 名儿童，包括 14 名健康男孩（HB）、13 名仍能行走的 DMD 男孩（DMD-RA）和 23 名丧失行走能力的 DMD 男孩（DMD-LA）。所有 DMD 男孩均接受了口服糖皮质激素治疗。使用外周定量计算机断层扫描测量非优势胫骨和桡骨的骨几何形状、密度、强度和肌肉质量。在基线、12 个月和 24 个月时，在远端干骺端和中段进行测量。使用方差分析和重复测量模型评估三组之间的差异。三组之间的年龄无显著差异：HB、DMD-RA 和 DMD-LA 的平均年龄分别为 9.4、8.7 和 8.8 岁。DMD 组之间的类固醇暴露无显著差异。然而，丧失行走能力的男孩在基线时肌肉功能明显较低（北星行走评估 DMD-RA 23.6 与 DMD-LA 18.8；p<0.05）。在基线时，健康男孩的远端桡骨/尺骨（23%/27%）和远端胫骨/腓骨（30%/46%）的骨小梁密度明显高于 DMD 男孩（p<0.05）。他们的骨干也明显较大（74%/36%），皮质较厚，因此骨强度更大。相比之下，DMD 男孩的皮质骨密度较高（4%）。随着时间的推移，健康男孩和 DMD 男孩的肌肉和骨骼参数的变化率都有微小的显著差异。对于仍能行走和不能行走的 DMD 男孩，皮质骨的最大变化都发生在胫骨。两年后，DMD 男孩的骨强度平均比健康男孩低 63%。然而，最显著的差异是不能行走的 DMD 男孩的骨小梁密度。2 年后，不能行走的 DMD 男孩的远端胫骨骨小梁密度比同龄健康男孩低 53%，而仍能行走的 DMD 男孩的骨小梁密度低 27%。总之，即使 DMD 男孩仍能行走，他们的骨骼和肌肉强度也会降低。然而，与仍能行走的 DMD 男孩相比，丧失独立行走能力的 DMD 男孩的胫骨小梁骨密度丢失明显加快，尽管他们接受了同等水平的皮质类固醇治疗。
