期刊
JOURNAL OF ENDOCRINOLOGY
卷 253, 期 2, 页码 63-74出版社
BIOSCIENTIFICA LTD
DOI: 10.1530/JOE-21-0388
关键词
bone QCT/micro CT; genetic animal models; GH/IGF-1; bone-muscle interactions
资金
- Medical Research Council/MDUK [MR/N020588/1]
- Biotechnology and Biological Sciences Research Council (BBSRC) for Institute Strategic Programme [BB/P0137321]
Short stature and osteoporosis are common in Duchenne muscular dystrophy (DMD). The abnormality of the GH/IGF-1 axis and long-term GC treatment may contribute to these conditions. An agent with anabolic properties that improve linear growth is needed and further exploration is required.
Short stature and osteoporosis are common in Duchenne muscular dystrophy (DMD) and its pathophysiology may include an abnormality of the growth hormone/insulin-like growth factor-1 (GH/IGF-1) axis, which is further exacerbated by long-term glucocorticoid (GC) treatment. Hence, an agent that has anabolic properties and may improve linear growth would be beneficial in this setting and therefore requires further exploration. A 5-week-old x-linked muscular dystrophy (mdx) mice were used as a model of DMD. They were treated with prednisolone +/- GH + IGF-1 for 4 weeks and then compared to control mdx mice to allow the study of both growth and skeletal structure. GC reduced cortical bone area, bone fraction, tissue area and volume and cortical bone volume, as assessed by micro computed tomography (CT) In addition, GC caused somatic and skeletal growth retardation but improved grip strength. The addition of GH + IGF-1 therapy rescued the somatic growth retardation and induced additional improvements in grip strength (16.9% increase, P < 0.05 compared to control). There was no improvement in bone microarchitecture (assessed by micro-CT and static histomorphometry) or biomechanical properties (assessed by three-point bending). Serum bone turnover markers (Serum procollagen 1 intact N-terminal propeptide (P1NP), alpha C-terminal telopeptide (alpha CTX)) also remained unaffected. Further work is needed to maximise these gains before proceeding to clinical trials in boys with DMD.
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