Hurley-Novatny Amelia, Chang David, Murakami Katsuhiro, Wang Ling, Li Hongshuai
Department of Orthopedics and Rehabilitation, University of Iowa, Iowa City, IA, United States.
Department of Anatomy and Cell Biology, University of Iowa, Iowa City, IA, United States.
Front Endocrinol (Lausanne). 2024 Nov 28;15:1398050. doi: 10.3389/fendo.2024.1398050. eCollection 2024.
Duchenne muscular dystrophy (DMD) is a progressive, fatal muscle wasting disease caused by X-linked mutations in the dystrophin gene. Alongside the characteristic muscle weakness, patients face a myriad of skeletal complications, including osteoporosis/osteopenia, high susceptibility to vertebral and long bone fractures, fat embolism post-fracture, scoliosis, and growth retardation. Those skeletal abnormalities significantly compromise quality of life and are sometimes life-threatening. These issues were traditionally attributed to loss of ambulation and chronic corticosteroid use, but recent investigations have unveiled a more intricate etiology. Factors such as vitamin D deficiency, hormonal imbalances, systemic inflammation, myokine release from dystrophic muscle, and vascular dysfunction are emerging as significant contributors as well. This expanded understanding illuminates the multifaceted pathogenesis underlying skeletal issues in DMD. Present therapeutic options are limited and lack specificity. Advancements in understanding the pathophysiology of bone complications in DMD will offer promising avenues for novel treatment modalities. In this review, we summarize the current understanding of factors contributing to bone problems in DMD and delineate contemporary and prospective multidisciplinary therapeutic approaches.
杜氏肌营养不良症(DMD)是一种进行性、致命的肌肉萎缩疾病,由肌营养不良蛋白基因的X连锁突变引起。除了典型的肌肉无力外,患者还面临着众多骨骼并发症,包括骨质疏松症/骨质减少、椎骨和长骨骨折的高易感性、骨折后脂肪栓塞、脊柱侧弯和生长发育迟缓。这些骨骼异常严重影响生活质量,有时甚至危及生命。这些问题传统上归因于活动能力丧失和长期使用皮质类固醇,但最近的研究揭示了一种更为复杂的病因。维生素D缺乏、激素失衡、全身炎症、营养不良肌肉释放的肌动蛋白以及血管功能障碍等因素也逐渐成为重要因素。这种更广泛的认识揭示了DMD骨骼问题背后的多方面发病机制。目前的治疗选择有限且缺乏特异性。对DMD骨并发症病理生理学认识的进展将为新型治疗方法提供有希望的途径。在这篇综述中,我们总结了目前对导致DMD骨问题的因素的认识,并描述了当代和未来的多学科治疗方法。