Glycogen Storage Disease Type I and Bone: Clinical and Cellular Characterization.

IF 3.3 3区 医学 Q2 ENDOCRINOLOGY & METABOLISM
Calcified Tissue International Pub Date : 2024-11-01 Epub Date: 2024-10-25 DOI:10.1007/s00223-024-01302-4
Silvia Vai, Alberto Falchetti, Sabrina Corbetta, Maria Luisa Bianchi, Chiara Alberio, Silvia Carrara, Serena Gasperini, Roberta Pretese, Loredana Parisi, Anna Teti, Antonio Maurizi
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Abstract

Glycogen storage disease (GSD) is the most prevalent inherited disorder of glycogen metabolism for which no causal treatment is available. In recent years, thanks to the improved clinical management, the life expectancy of these patients extended, disclosing previously unidentified adverse conditions in other organs. In this study, we evaluated the clinical bone complications and the cellular responses in 20 patients (aged 14.1 ± 3.4 years) affected by GSD type I. Fragility fractures were reported in 35% of the patients, which were older than unfractured patients. They involved appendicular skeletal segments, while no vertebral deformity was detected. 60% of the patients had a bone mineral density (BMD) "below the expected range for age", and lumbar spine (LS) BMD Z-scores positively correlated with muscle strength. Circulating mineral and bone markers showed reduction in the older subjects, with no increase in the pubertal age. Significant correlations could not be detected between circulating markers and LS BMD Z-scores, except for sclerostin levels, which also correlated with muscle strength. The osteoclasts differentiated from patients' peripheral blood mononuclear cells did not show cell-autonomous alterations. However, circulating osteoclast precursors from healthy individuals cultured in the presence of patients' sera exhibited increased osteoclastogenesis compared to control sera suggesting that GSD type I serum factors could affect osteoclast function in a non-autonomous manner. In contrast, circulating osteoprogenitors were unremarkable.

糖原贮积症 I 型和骨:临床和细胞特征。
糖原贮积病(GSD)是最常见的遗传性糖原代谢疾病,目前尚无治疗方法。近年来,由于临床治疗水平的提高,这些患者的寿命得以延长,但在其他器官却出现了之前未被发现的不良状况。在这项研究中,我们评估了 20 名 I 型 GSD 患者(年龄为 14.1 ± 3.4 岁)的临床骨骼并发症和细胞反应。这些骨折涉及附属骨骼,但未发现脊椎畸形。60%的患者骨质密度(BMD)"低于预期年龄范围",腰椎骨质密度 Z 值与肌肉力量呈正相关。血液循环中的矿物质和骨标记物在年龄较大的受试者中有所减少,而在青春期年龄中没有增加。除硬骨素水平与肌肉力量相关外,循环标志物与腰椎骨密度 Z 值之间未发现明显的相关性。从患者外周血单核细胞中分化出的破骨细胞并未出现细胞自主性改变。然而,与对照血清相比,在患者血清存在的情况下培养的健康人循环破骨细胞前体显示出破骨细胞生成增加,这表明 GSD I 型血清因子可能以非自主方式影响破骨细胞功能。与此相反,循环中的成骨细胞并无异常。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Calcified Tissue International
Calcified Tissue International 医学-内分泌学与代谢
CiteScore
8.00
自引率
2.40%
发文量
112
审稿时长
4-8 weeks
期刊介绍: Calcified Tissue International and Musculoskeletal Research publishes original research and reviews concerning the structure and function of bone, and other musculoskeletal tissues in living organisms and clinical studies of musculoskeletal disease. It includes studies of cell biology, molecular biology, intracellular signalling, and physiology, as well as research into the hormones, cytokines and other mediators that influence the musculoskeletal system. The journal also publishes clinical studies of relevance to bone disease, mineral metabolism, muscle function, and musculoskeletal interactions.
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