Bone and Muscle Interactions in Bone Pathologies

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Background

Several bone pathologies such as bone metastases, cancer treatment-induced bone loss, osteoporosis, Paget’s diseases, calcium or vitamin D deficiency, are associated with increased bone destruction or increased bone remodeling that causes fracture, pain, and may lead to muscle weakness. Bone and muscle are tightly integrated tissues and due to their tight physical attachment, molecular exchange between bone and muscle helps in providing functional support. Active research is underway to understand the mechanisms of bone and muscle cross- talk which can have therapeutic advantages to treat musculoskeletal diseases. It is widely known that abnormal bone destruction releases factors from bone matrix which causes muscle weakness. Similarly, myokines release from muscle atrophy or conditions of muscle dysfunction may impair normal bone hemostasis. Abnormal bone resorption can cause bone pain which can be associated with mobility limitations in patients. Muscle weakness can unload the bone to further increase bone resorption which can potentially increase risk of fractures and fall. If excess bone resorption is associated with muscle weakness then it may increase fracture risk, may reduce the therapeutic response of currently available bone-targets therapeutics, and reduce survival. Thus, it is urgent to understand the role of bone derived factors in muscle weakness. Similarly, it is important to identify the mechanisms of bone loss in the settings of muscle dysfunction.

Interaction of bone-derived factors with muscle function is an evolving area of research. Similarly, muscle weakness either due to loss of muscle mass or due to loss of muscle function or combination of both can dysregulate physiological balance in bone cells. Cancer cachexia, fatty infiltration in muscle, lack of exercise, sarcopenia, muscle injury, hormonal imbalances cause abnormal release of muscle derived actors which can interfere with bone remodeling process to lead pathological bone destruction. Treatments of cancer such as radiation therapy, endocrine therapy or chemotherapy are known factors to cause bone loss. However, how these therapeutics impact muscle metabolism is an area of future research. For the better management of bone diseases associated with muscle weakness; identification of molecular targets which can simultaneously prevent bone loss and associated muscle weakness is necessary. Preventing these effects by blocking pathological bone destruction can improve bone quality, muscle weakness and reduce fractures. Similarly, molecular targets which can prevent muscle dysfunction and indirectly bone loss could have better therapeutic advantage. Exercise, nutrition and regulation of circadian rhythm known for their positive effects on musculoskeletal system. Testing of these factors in different bone pathologies could improve the morbidity of the patients suffering from debilitating complications of bone loss and muscle weakness. It would also be beneficial to discover if currently available bone-targeted therapeutic have direct impact on skeletal muscle metabolism.

The scope of this topic is to collect original research articles, review articles, mini-reviews, case reports or short communication that discuss: 1) how various bone pathologies interfere with muscle metabolism (regulation of both muscle mass and/or muscle function); 2) how muscle abnormalities can negatively impact bone remodeling (cellular communication in bone cells)
Below are some examples of topics that can be covered:

- Molecular interactions between bone and muscle in different conditions of pathologic bone remodeling;

- Impact of cancer treatments on muscle metabolism;

- How exosomes or microRNA can regulate the crosstalk between bone and muscle in bone diseases;

- Effects of bone-targeted agents on prevention of muscle weakness;

- Combination treatment of bone targeted therapeutics and agents to improve muscle mass in prevention/cure of musculoskeletal diseases;

- Effects of unloading, immobility on bone and muscle biomechanics;

- Emerging exercise interventions for musculoskeletal diseases;

- Nutrition studies and their impact on bone and muscle crosstalk;

- Effects of muscle weakness on bone quality;

- Novel signaling molecules release from muscle to act on bone cells;

- Muscle atrophy or injury and their impact on bone;

- Impact of hormone deprivation therapies on muscle-bone cross talk;

- Impact of bone derived factors on calcium homeostasis in skeletal muscle;

- Dysregulation muscle calcium release, muscle mitochondrial metabolism, muscle oxidative stress in states of excessive bone resorption.

Keywords: Pathologic bone destruction, musculoskeletal, bone resorption, bone remodeling, skeletal muscle, bone marrow adiposity, oxidative stress, myokines, bone-targeted therapies.

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

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