Low intensity vibration mitigates tumor progression and protects bone quantity and quality in a murine model of myeloma.
Myeloma facilitates destruction of bone and marrow. Since physical activity encourages musculoskeletal preservation we evaluated whether low-intensity vibration (LIV), a means to deliver mechanical signals, could protect bone and marrow during myeloma progression. Immunocompromised-mice (n=25) were injected with human-myeloma cells, while 8 (AC) were saline-injected. Myeloma-injected mice (LIV; n=13) were subjected to daily-mechanical loading (15min/d; 0.3g @ 90Hz) while 12 (MM) were sham-handled. At 8w, femurs had 86% less trabecular bone volume fraction (BV/TV) in MM than in AC, yet only a 21% decrease in LIV was observed in comparison to AC, reflecting a 76% increase versus MM. Cortical BV was 21% and 15% lower in MM and LIV, respectively, than in AC; LIV showing 30% improvement over MM. Similar outcomes were observed in the axial skeleton, showing a 35% loss in MM with a 27% improved retention of bone in the L5 of LIV-treated mice as compared to MM. Transcortical-perforations in the femur from myeloma-induced osteolysis were 9× higher in MM versus AC, reduced by 57% in LIV. Serum-TRACP5b, 61% greater in MM versus AC, rose by 33% in LIV compared to AC, a 45% reduction in activity when compared to MM. Histomorphometric analyses of femoral trabecular bone demonstrated a 70% elevation in eroded surfaces of MM versus AC, while measures in LIV were 58% below those in MM. 72% of marrow in the femur of MM mice contained tumor, contrasted by a 31% lower burden in LIV. MM mice (42%) presented advanced-stage necrosis of tibial marrow while present in just 8% of LIV. Myeloma infiltration inversely correlated to measures of bone quality, while LIV slowed the systemic, myeloma-associated decline in bone quality and inhibited tumor progression through the hindlimbs.
Department of Biomedical Engineering, Stony Brook University, Stony Brook, NY 11794-5281, United States.
Gabriel M
GM
Pagnotti
Department of Biomedical Engineering, Stony Brook University, Stony Brook, NY 11794-5281, United States.
M Ete
ME
Chan
Department of Biomedical Engineering, Stony Brook University, Stony Brook, NY 11794-5281, United States.
Benjamin J
BJ
Adler
Department of Pathology, Stony Brook University, Stony Brook, NY 11794-2580, United States.
Kenneth R
KR
Shroyer
Department of Medicine, University of North Carolina, Chapel Hill, NC 27599, United States.
Janet
J
Rubin
Department of Orthopedics & Sports Medicine, University of Washington, Seattle, WA 98104-2499, United States.
Steven D
SD
Bain
Department of Biomedical Engineering, Stony Brook University, Stony Brook, NY 11794-5281, United States. Electronic address: clinton.rubin@stonybrook.edu.
Clinton T
CT
Rubin
D000818:Animals; D001853:Bone Marrow / Q000473:pathology; D001842:Bone and Bones / Q000473:pathology*; D045744:Cell Line, Tumor; D000071538:Cortical Bone / Q000473:pathology; D004195:Disease Models, Animal; D018450:Disease Progression; D005269:Femur / Q000000981:diagnostic imaging / Q000473:pathology; D005434:Flow Cytometry; D006410:Hematopoiesis; D006801:Humans; D040542:Mechanotransduction, Cellular; D009101:Multiple Myeloma / Q000000981:diagnostic imaging / Q000276:immunology / Q000473:pathology*; D010010:Osteoclasts / Q000473:pathology; D000071681:Tartrate-Resistant Acid Phosphatase / Q000378:metabolism; D014732:Vibration; D055114:X-Ray Microtomography
D000071681:Tartrate-Resistant Acid Phosphatase
Bone marrow; Cancer-induced bone disease; Exercise; Low intensity vibration; Mechanical signals; Myeloma; Osteopenia