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Review
. 2021 Dec;19(6):580-591.
doi: 10.1007/s11914-021-00704-9. Epub 2021 Nov 3.

Mechanobiology of Bone Metastatic Cancer

Blayne A Sarazin  1 , Claire L Ihle  2 , Philip Owens  2   3 , Maureen E Lynch  4   5
Affiliations
Review

Mechanobiology of Bone Metastatic Cancer

Blayne A Sarazin et al. Curr Osteoporos Rep. 2021 Dec.

Abstract

Purpose of review: In this review, we provide an overview of what is currently known about the impacts of mechanical stimuli on metastatic tumor-induced bone disease (TIBD). Further, we focus on the role of the osteocyte, the skeleton's primary mechanosensory cell, which is central to the skeleton's mechanoresponse, sensing and integrating local mechanical stimuli, and then controlling the downstream remodeling balance as appropriate.

Recent findings: Exercise and controlled mechanical loading have anabolic effects on bone tissue in models of bone metastasis. They also have anti-tumorigenic properties, in part due to offsetting the vicious cycle of osteolytic bone loss as well as regulating inflammatory signals. The impacts of metastatic cancer on the mechanosensory function of osteocytes remains unclear. Increased mechanical stimuli are a potential method for mitigating TIBD.

Keywords: Bone metastasis; Bone remodeling; Mechanical loading; Osteocytes; Tumor-induced bone disease.

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Conflict of interest statement

Conflict of Interest The authors declare no competing interests.

Figures

Fig. 1
Fig. 1. Bone remodeling scenarios.
Healthy remodeling is characterized by balanced osteoclastic resorption and osteoblastic formation. When mechanical stimuli increases, for example due to exercise, the remodeling balance shifts towards formation. Increased loading promotes osteogenic differentiation of osteoblast progenitors (i.e. MSCs), osteoblast activity, and inhibits both osteoblast apoptosis and osteoclast activity. In contrast, during osteolytic bone metastatic cancer, tumor cells secrete PTHrP to stimulate osteoblast RANKL production, thereby stimulating osteoclastic resorption. In the process, growth factors are liberated from bone tissue that literally feed the tumor cells, thereby establishing a positive feedback loop known as the ‘vicious cycle’ [37]
Fig. 2
Fig. 2. Generation of loading-induced fluid flow within the LCN.
A) Osteocytes are situated within the lacunocanalicular network (LCN), which is filled with extracellular fluid. B) Upon loading, the hydrated tissue deforms, pressurizing the fluid within. Fluid flows over osteocytes, from zones of high pressure to low pressure
See this image and copyright information in PMC

References

    1. Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer Statistics, 662 2021. CA: A Cancer Journal for Clinicians. 2021;7(1);7–33. 10.3322/caac.21654. - DOI - PubMed
    1. Saad F, Gleason DM, Murray R, Tchekmedyian S, Venner P, Lacombe L, Chin JL, Vinholes JJ, Goas JA, Zheng M, Zoledronic Acid Prostate Cancer Study Group. Long-term efficacy of zoledronic acid for the prevention of skeletal complications in patients with metastatic hormone-refractory prostate cancer. J. Natl. Cancer Inst. 2004;96(11):879–82. - PubMed
    1. Grill V, Martin TJ. Hypercalcemia of malignancy. Rev. Endocr. Metab. Disord. 2000;1(4):253–63. - PubMed
    1. Cheung AM, Giangregorio L. Mechanical stimuli and bone health: what is the evidence? Curr. Opin. Rheumatol. 2012;24(5):561–6. - PubMed
    1. Friedenreich CM, Stone CR, Cheung WY, Hayes SC. Physical activity and mortality in cancer survivors: a systematic review and meta-analysis. JNCI Cancer Spectr. 2020;4(1):pkz080. - PMC - PubMed

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