Suppression of cancer-associated bone loss through dynamic mechanical loading

• Published in: Bone (New York, N.Y.) Vol. 150; p. 115998
• Main Authors: Pagnotti, G.M., Thompson, W.R., Guise, T.A., Rubin, C.T.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.09.2021
• Subjects: Bone and Bones; Bone Diseases, Metabolic; Bone remodeling; Breast cancer bone metastases; Cancer-associated bone disease; Humans; Low intensity vibrations; Low magnitude mechanical signals; Mechanical loading; Mechanotransduction, Cellular; Multiple myeloma; Neoplasms; Osteolytic lesions; Osteoporosis; Stress, Mechanical; Cancer-associated bone disease; Mechanical loading; Multiple myeloma; Low magnitude mechanical signals; Breast cancer bone metastases; Bone remodeling; Low intensity vibrations; Osteolytic lesions
• ISSN: 8756-3282; 1873-2763
• DOI: 10.1016/j.bone.2021.115998

Patients afflicted with or being treated for cancer constitute a distinct and alarming subpopulation who exhibit elevated fracture risk and heightened susceptibility to developing secondary osteoporosis. Cancer cells uncouple the regulatory processes central for the adequate regulation of musculoskeletal tissue. Systemically taxing treatments to target tumors or disrupt the molecular elements driving tumor growth place considerable strain on recovery efforts. Skeletal tissue is inherently sensitive to mechanical forces, therefore attention to exercise and mechanical loading as non-pharmacological means to preserve bone during treatment and in post-treatment rehabilitative efforts have been topics of recent focus. This review discusses the dysregulation that cancers and the ensuing metabolic dysfunction that confer adverse effects on musculoskeletal tissues. Additionally, we describe foundational mechanotransduction pathways and the mechanisms by which they influence both musculoskeletal and cancerous cells. Functional and biological implications of mechanical loading at the tissue and cellular levels will be discussed, highlighting the current understanding in the field. Herein, in vitro, translational, and clinical data are summarized to consider the positive impact of exercise and low magnitude mechanical loading on tumor-bearing skeletal tissue. •Mechanical unloading, sedentary behavior and metastatic cancer result in bone loss.•Various mechanical stimuli preserve bone mass and reduce bone resorption.•Mechanical signals reduce tumor burden in animal and cell-based cancer models.•Membrane-bound actin-fibers transduce mechanical stimuli into the nucleus via LINC.•Mechanical signals decrease metastatic cancer cell proliferation and migration.