Beyond Muscle Weakness: Unraveling Endocrine and Metabolic Dysfunctions in Duchenne Muscular Dystrophy, a Narrative Review
<b>Background:</b> Duchenne muscular dystrophy (DMD) is a severe X-linked neuromuscular disorder caused by mutations in the <i>DMD</i> gene, leading to progressive muscle degeneration, loss of ambulation, and multi-systemic complications. Beyond its impact on mobility, DMD is...
Saved in:
| Main Authors: | , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2025-07-01
|
| Series: | Biomedicines |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2227-9059/13/7/1613 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849407672133091328 |
|---|---|
| author | Giuseppe Cannalire Giacomo Biasucci Vanessa Sambati Tommaso Toschetti Arianna Maria Bellani Anna-Mariia Shulhai Federica Casadei Erika Rita Di Bari Francesca Ferraboschi Cecilia Parenti Maria Carmela Pera Susanna Esposito Maria Elisabeth Street |
| author_facet | Giuseppe Cannalire Giacomo Biasucci Vanessa Sambati Tommaso Toschetti Arianna Maria Bellani Anna-Mariia Shulhai Federica Casadei Erika Rita Di Bari Francesca Ferraboschi Cecilia Parenti Maria Carmela Pera Susanna Esposito Maria Elisabeth Street |
| author_sort | Giuseppe Cannalire |
| collection | DOAJ |
| description | <b>Background:</b> Duchenne muscular dystrophy (DMD) is a severe X-linked neuromuscular disorder caused by mutations in the <i>DMD</i> gene, leading to progressive muscle degeneration, loss of ambulation, and multi-systemic complications. Beyond its impact on mobility, DMD is associated with significant endocrine and metabolic dysfunctions that develop over time. <b>Objective:</b> To provide a comprehensive analysis of growth disturbances, endocrine dysfunctions, and metabolic complications in DMD including bone metabolism, considering the underlying mechanisms, clinical implications, and management strategies for daily clinical guidance. <b>Methods:</b> In this narrative review, an evaluation of the literature was conducted by searching the Medline database via the PubMed, Scopus, and Web of Science interfaces. <b>Results:</b> Growth retardation is a hallmark feature of DMD, with patients exhibiting significantly shorter stature compared to their healthy peers. This is exacerbated by long-term glucocorticoid therapy, which disrupts the growth hormone/insulin-like growth factor-1 (GH/IGF-1) axis and delays puberty. Obesity prevalence follows a biphasic trend, with increased risk in early disease stages due to reduced mobility and corticosteroid use, followed by a decline in body mass index (BMI) in later stages due to muscle wasting. Metabolic complications, including insulin resistance, altered lipid metabolism, and hepatic steatosis, further characterize disease burden. Osteoporosis and increased fracture risk, primarily due to reduced mechanical loading and glucocorticoid-induced bone resorption, are major concerns, needing early screening and intervention. The RANK/RANKL/OPG signaling pathway has emerged as a critical factor in bone deterioration, providing potential therapeutic targets for improving skeletal health. <b>Conclusions:</b> Growth and endocrine disorders in DMD are complex and multifactorial, requiring proactive monitoring and early intervention. Addressing these issues requires a multidisciplinary approach integrating endocrine, nutritional, and bone health management. Further research is essential to refine treatment strategies that mitigate growth and metabolic disturbances while preserving overall patient well-being. |
| format | Article |
| id | doaj-art-e24a2fefb0d54b30a81c24b7e26a2c6f |
| institution | Kabale University |
| issn | 2227-9059 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj-art-e24a2fefb0d54b30a81c24b7e26a2c6f2025-08-20T03:35:58ZengMDPI AGBiomedicines2227-90592025-07-01137161310.3390/biomedicines13071613Beyond Muscle Weakness: Unraveling Endocrine and Metabolic Dysfunctions in Duchenne Muscular Dystrophy, a Narrative ReviewGiuseppe Cannalire0Giacomo Biasucci1Vanessa Sambati2Tommaso Toschetti3Arianna Maria Bellani4Anna-Mariia Shulhai5Federica Casadei6Erika Rita Di Bari7Francesca Ferraboschi8Cecilia Parenti9Maria Carmela Pera10Susanna Esposito11Maria Elisabeth Street12Pediatrics and Neonatology Unit, University of Parma, Guglielmo da Saliceto Hospital, 29121 Piacenza, ItalyPediatrics and Neonatology Unit, University of Parma, Guglielmo da Saliceto Hospital, 29121 Piacenza, ItalyDepartment of Medicine and Surgery, University of Parma, 43126 Parma, ItalyDepartment of Medicine and Surgery, University of Parma, 43126 Parma, ItalyDepartment of Medicine and Surgery, University of Parma, 43126 Parma, ItalyDepartment of Medicine and Surgery, University of Parma, 43126 Parma, ItalyDepartment of Medicine and Surgery, University of Parma, 43126 Parma, ItalyDepartment of Medicine and Surgery, University of Parma, 43126 Parma, ItalyDepartment of Medicine and Surgery, University of Parma, 43126 Parma, ItalyDepartment of Medicine and Surgery, University of Parma, 43126 Parma, ItalyDepartment of Medicine and Surgery, University of Parma, 43126 Parma, ItalyDepartment of Medicine and Surgery, University of Parma, 43126 Parma, ItalyDepartment of Medicine and Surgery, University of Parma, 43126 Parma, Italy<b>Background:</b> Duchenne muscular dystrophy (DMD) is a severe X-linked neuromuscular disorder caused by mutations in the <i>DMD</i> gene, leading to progressive muscle degeneration, loss of ambulation, and multi-systemic complications. Beyond its impact on mobility, DMD is associated with significant endocrine and metabolic dysfunctions that develop over time. <b>Objective:</b> To provide a comprehensive analysis of growth disturbances, endocrine dysfunctions, and metabolic complications in DMD including bone metabolism, considering the underlying mechanisms, clinical implications, and management strategies for daily clinical guidance. <b>Methods:</b> In this narrative review, an evaluation of the literature was conducted by searching the Medline database via the PubMed, Scopus, and Web of Science interfaces. <b>Results:</b> Growth retardation is a hallmark feature of DMD, with patients exhibiting significantly shorter stature compared to their healthy peers. This is exacerbated by long-term glucocorticoid therapy, which disrupts the growth hormone/insulin-like growth factor-1 (GH/IGF-1) axis and delays puberty. Obesity prevalence follows a biphasic trend, with increased risk in early disease stages due to reduced mobility and corticosteroid use, followed by a decline in body mass index (BMI) in later stages due to muscle wasting. Metabolic complications, including insulin resistance, altered lipid metabolism, and hepatic steatosis, further characterize disease burden. Osteoporosis and increased fracture risk, primarily due to reduced mechanical loading and glucocorticoid-induced bone resorption, are major concerns, needing early screening and intervention. The RANK/RANKL/OPG signaling pathway has emerged as a critical factor in bone deterioration, providing potential therapeutic targets for improving skeletal health. <b>Conclusions:</b> Growth and endocrine disorders in DMD are complex and multifactorial, requiring proactive monitoring and early intervention. Addressing these issues requires a multidisciplinary approach integrating endocrine, nutritional, and bone health management. Further research is essential to refine treatment strategies that mitigate growth and metabolic disturbances while preserving overall patient well-being.https://www.mdpi.com/2227-9059/13/7/1613Duchenne muscular dystrophygrowth impairmentendocrine dysfunctionmetabolic alterationsosteoporosispuberty delay |
| spellingShingle | Giuseppe Cannalire Giacomo Biasucci Vanessa Sambati Tommaso Toschetti Arianna Maria Bellani Anna-Mariia Shulhai Federica Casadei Erika Rita Di Bari Francesca Ferraboschi Cecilia Parenti Maria Carmela Pera Susanna Esposito Maria Elisabeth Street Beyond Muscle Weakness: Unraveling Endocrine and Metabolic Dysfunctions in Duchenne Muscular Dystrophy, a Narrative Review Biomedicines Duchenne muscular dystrophy growth impairment endocrine dysfunction metabolic alterations osteoporosis puberty delay |
| title | Beyond Muscle Weakness: Unraveling Endocrine and Metabolic Dysfunctions in Duchenne Muscular Dystrophy, a Narrative Review |
| title_full | Beyond Muscle Weakness: Unraveling Endocrine and Metabolic Dysfunctions in Duchenne Muscular Dystrophy, a Narrative Review |
| title_fullStr | Beyond Muscle Weakness: Unraveling Endocrine and Metabolic Dysfunctions in Duchenne Muscular Dystrophy, a Narrative Review |
| title_full_unstemmed | Beyond Muscle Weakness: Unraveling Endocrine and Metabolic Dysfunctions in Duchenne Muscular Dystrophy, a Narrative Review |
| title_short | Beyond Muscle Weakness: Unraveling Endocrine and Metabolic Dysfunctions in Duchenne Muscular Dystrophy, a Narrative Review |
| title_sort | beyond muscle weakness unraveling endocrine and metabolic dysfunctions in duchenne muscular dystrophy a narrative review |
| topic | Duchenne muscular dystrophy growth impairment endocrine dysfunction metabolic alterations osteoporosis puberty delay |
| url | https://www.mdpi.com/2227-9059/13/7/1613 |
| work_keys_str_mv | AT giuseppecannalire beyondmuscleweaknessunravelingendocrineandmetabolicdysfunctionsinduchennemusculardystrophyanarrativereview AT giacomobiasucci beyondmuscleweaknessunravelingendocrineandmetabolicdysfunctionsinduchennemusculardystrophyanarrativereview AT vanessasambati beyondmuscleweaknessunravelingendocrineandmetabolicdysfunctionsinduchennemusculardystrophyanarrativereview AT tommasotoschetti beyondmuscleweaknessunravelingendocrineandmetabolicdysfunctionsinduchennemusculardystrophyanarrativereview AT ariannamariabellani beyondmuscleweaknessunravelingendocrineandmetabolicdysfunctionsinduchennemusculardystrophyanarrativereview AT annamariiashulhai beyondmuscleweaknessunravelingendocrineandmetabolicdysfunctionsinduchennemusculardystrophyanarrativereview AT federicacasadei beyondmuscleweaknessunravelingendocrineandmetabolicdysfunctionsinduchennemusculardystrophyanarrativereview AT erikaritadibari beyondmuscleweaknessunravelingendocrineandmetabolicdysfunctionsinduchennemusculardystrophyanarrativereview AT francescaferraboschi beyondmuscleweaknessunravelingendocrineandmetabolicdysfunctionsinduchennemusculardystrophyanarrativereview AT ceciliaparenti beyondmuscleweaknessunravelingendocrineandmetabolicdysfunctionsinduchennemusculardystrophyanarrativereview AT mariacarmelapera beyondmuscleweaknessunravelingendocrineandmetabolicdysfunctionsinduchennemusculardystrophyanarrativereview AT susannaesposito beyondmuscleweaknessunravelingendocrineandmetabolicdysfunctionsinduchennemusculardystrophyanarrativereview AT mariaelisabethstreet beyondmuscleweaknessunravelingendocrineandmetabolicdysfunctionsinduchennemusculardystrophyanarrativereview |