title: Low magnitude mechanical signals mitigate osteopenia without compromising longevity in an aged murine model of spontaneous granulosa cell ovarian cancer.
abstract: Cancer progression is often paralleled by a decline in bone mass, raising risk of fracture. Concerns persist regarding anabolic interventions for skeletal protection, as these may inadvertently exacerbate neoplastic tissue expansion. Given bone's inherent mechanosensitivity, low intensity vibration (LIV), a mechanical signal that encourages osteoblastogenesis, could possibly slow cancer-associated bone loss, but this goal must be achieved without fostering disease progression. Seventy 12w female F1-SWRxSWXJ-9 mice, a strain prone to developing granulosa cell tumors, were randomized into baseline control (BC: n=10), age-matched control (AC: n=30), and LIV (n=30), which received mechanical signals (90Hz @ 0.3g) for 15m/day, 5 day/w over the course of 1 year. Survival curves for AC (10 died) and LIV (8 died) followed similar trends (p=0.62), indicating longevity was unperturbed by LIV. At 1 year, bone volume of proximal tibiae in LIV mice was 25% greater than AC (p<0.02), while bone volume of L5 vertebrae was 16% higher in LIV over AC (p<0.02). Primary lesions and peripheral metastases were apparent in both LIV and AC; however, overall tumor incidence was approximately 30% less in LIV (p=0.27) and, when disease was evident, involved fewer organ systems (p=0.09). Marrow-derived mesenchymal stem cells (MSC) were 52% lower (p<0.01) in LIV, and 31% lower (p=0.08) in mice lacking pathology, suggesting higher MSC levels in this model of cancer susceptibility may have contributed to tumor progression. These experiments indicate that LIV helps protect bone mass in mice inherently susceptible to cancer without compromising life expectancy, perhaps through mechanical control of stem cell fate. Further, these data reflect the numerous system-level benefits of exercise in general, and mechanical signals in particular, in the preservation of bone density and the suppression of cancer progression.
authors.affiliation: Department of Biomedical Engineering, Stony Brook University, Stony Brook, NY 11794-2580, USA.
authors.forename: Gabriel M
authors.initials: GM
authors.lastname: Pagnotti
authors.forename: Benjamin J
authors.initials: BJ
authors.lastname: Adler
authors.forename: Danielle E
authors.initials: DE
authors.lastname: Green
authors.forename: M Ete
authors.initials: ME
authors.lastname: Chan
authors.forename: Danielle M
authors.initials: DM
authors.lastname: Frechette
authors.forename: Kenneth R
authors.initials: KR
authors.lastname: Shroyer
authors.forename: Wesley G
authors.initials: WG
authors.lastname: Beamer
authors.forename: Janet
authors.initials: J
authors.lastname: Rubin
authors.forename: Clinton T
authors.initials: CT
authors.lastname: Rubin
mesh_terms: D000818:Animals; D001851:Bone Diseases, Metabolic / Q000000981:diagnostic imaging / Q000473:pathology / Q000517:prevention & control*; D001853:Bone Marrow / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D005434:Flow Cytometry; D006106:Granulosa Cell Tumor / Q000150:complications* / Q000000981:diagnostic imaging / Q000473:pathology*; D006614:Hindlimb / Q000473:pathology; D007091:Image Processing, Computer-Assisted; D008136:Longevity; D059630:Mesenchymal Stem Cells / Q000166:cytology; D051379:Mice; D009929:Organ Size; D010051:Ovarian Neoplasms / Q000150:complications* / Q000000981:diagnostic imaging / Q000473:pathology*; D016019:Survival Analysis; D013977:Tibia / Q000000981:diagnostic imaging / Q000473:pathology; D014732:Vibration; D055114:X-Ray Microtomography