Background: Duchenne muscular dystrophy (DMD) is a severe X-linked neuromuscular disorder caused by mutations in the DMD 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. Objective: 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. Methods: 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. Results: 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. Conclusions: 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.
Beyond Muscle Weakness: Unraveling Endocrine and Metabolic Dysfunctions in Duchenne Muscular Dystrophy, a Narrative Review / Cannalire, G.; Biasucci, G.; Sambati, V.; Toschetti, T.; Bellani, A. M.; Shulhai, A. M.; Casadei, F.; Di Bari, E. R.; Ferraboschi, F.; Parenti, C.; Pera, M. C.; Esposito, S.; Street, M. E.. - In: BIOMEDICINES. - ISSN 2227-9059. - 13:7(2025). [10.3390/biomedicines13071613]
Beyond Muscle Weakness: Unraveling Endocrine and Metabolic Dysfunctions in Duchenne Muscular Dystrophy, a Narrative Review
Biasucci G.
;Sambati V.;Toschetti T.;Bellani A. M.;Shulhai A. M.;Casadei F.;Di Bari E. R.;Ferraboschi F.;Parenti C.;Pera M. C.;Esposito S.;Street M. E.
2025-01-01
Abstract
Background: Duchenne muscular dystrophy (DMD) is a severe X-linked neuromuscular disorder caused by mutations in the DMD 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. Objective: 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. Methods: 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. Results: 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. Conclusions: 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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
