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Bone-Muscle Crosstalk: Unraveling New Therapeutic Targets for Osteoporosis
Anna Picca1, Riccardo Calvani1, Ester Manes-Gravina1
1Center for Geriatrics, Neurosciences, Ear Nose and Throat, and Orthopedics, Catholic University of the Sacred Heart, Teaching Hospital "Agostino Gemelli", Rome 00168, Italy.
Abstract:
Osteoporosis is a condition featured by bone mass loss and bone tissue microarchitectural alterations due to impaired tissue homeostasis favoring excessive bone resorption versus deposition. The trigger of such an impairment and the downstream molecular pathways involved are yet to be clarified. The natural course of osteoporosis is particularly worrisome because, through a "silent" progression, it enhances bone fragility, increases the risk of fractures and is associated with increased risk of disability and mortality. To date, the assessment of bone mineral density by dual-energy X-ray absorptiometry, represents the non-invasive gold standard for the evaluation of bone mineralization and the diagnosis of osteoporosis. Although long known as a condition merely related to the hormonal-driven loss of bone homeostasis, emerging evidence supports the need of reframing osteoporosis in the context of structural and functional changes of the musculoskeletal system as a whole. Several age-related alterations of bone microenvironment and an altered bone-muscle crosstalk have been suggested to be relevant contributors to loss of bone strength and mass characterizing osteoporosis. The present work provides an overview of the current knowledge of the pathophysiology of osteoporosis obtained through advances in epigenetics, cell biology and osteoimmunology. In light of the increasingly recognized importance of bone-muscle interconnection, this review also discusses relevant pathways that may be dissected for identifying new therapeutic targets for age-related musculoskeletal degeneration.
Insights
Osteoporosis involves bone loss and microarchitectural changes, increasing fracture risk. Emerging research highlights the crucial role of bone-muscle interactions in its pathophysiology and potential new therapeutic targets.
Area of Science:
- Bone Biology and Musculoskeletal Health
- Cell Biology and Epigenetics
- Osteoimmunology
Background:
- Osteoporosis is characterized by reduced bone mass and microarchitectural deterioration, leading to increased fracture risk, disability, and mortality.
- While traditionally linked to hormonal changes, recent evidence suggests a broader context involving musculoskeletal system alterations and impaired bone-muscle crosstalk.
- The precise triggers and molecular pathways underlying osteoporosis pathophysiology remain incompletely understood.
Purpose of the Study:
- To provide a comprehensive overview of osteoporosis pathophysiology.
- To explore the role of epigenetics, cell biology, and osteoimmunology in bone homeostasis.
- To discuss the significance of bone-muscle interactions in age-related musculoskeletal degeneration and identify potential therapeutic targets.
Main Methods:
- Review of current scientific literature on osteoporosis.
- Analysis of advances in epigenetics, cell biology, and osteoimmunology.
- Examination of age-related changes in bone microenvironment and bone-muscle crosstalk.
Main Results:
- Osteoporosis pathophysiology involves complex interactions beyond hormonal influences.
- Epigenetic, cellular, and immune factors significantly contribute to bone loss.
- Altered bone-muscle communication is a key factor in age-related bone degeneration.
Conclusions:
- Reframing osteoporosis requires understanding its connection to the broader musculoskeletal system.
- Investigating bone-muscle interconnection offers promising avenues for novel therapeutic strategies.
- Further research into the molecular pathways of osteoporosis is essential for developing effective treatments.
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