ArticleBone2021
Moderate tibial loading and treadmill running, but not overloading, protect adult murine bone from destruction by metastasized breast cancer.
Article in Bone, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
20 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Methodological aspects ofJournal of musculoskeletal & neuronal interactions · 2023Pooled it
- Bone Multicellular Unit on a Chip (BMU-Chip) Subjected to Cyclic Mechanical Loading.ACS biomaterials science & engineering · 2026Article
- Engineered bone matrix models for understanding breast cancer skeletal metastasis.Cancer metastasis reviews · 2026Review
- Osteocytes under Mechanical Loading Regulate PC-3 Cancer Cell-Mineral Interactions during Early-Stage Metastasis to Bone.Advanced biology · 2025Article
- 3D Osteocyte Networks under Pulsatile Unidirectional Fluid Flow Stimuli (PUFFS).ACS biomaterials science & engineering · 2025Article
- Article
- Prognostic assessment of osteolytic lesions and mechanical properties of bones bearing breast cancer using neural network and finite element analysisMechanobiology in medicine · 2025Article
- Article
- Physical activity enhances the effect of immune checkpoint blockade by inhibiting the intratumoral HIF1-α/CEACM1 axis.Journal of molecular histology · 2024Article
- Article
- Role of the osteocyte in bone metastasis - The importance of networking.Journal of bone oncology · 2024Article
- Exercise improves cognitive dysfunction and neuroinflammation in mice through Histone H3 lactylation in microglia.Immunity & ageing : I & A · 2023Article
- Review
- Reduction of breast cancer extravasation via vibration activated osteocyte regulation.iScience · 2022Article
- Microfluidic Co-culture Platforms for Studying Osteocyte Regulation of Other Cell Types under Dynamic Mechanical Stimulation.Current osteoporosis reports · 2022Review
- Effects of Whole-Body Vibration on Breast Cancer Bone Metastasis and Vascularization in Mice.Calcified tissue international · 2022Article
- Yoda1 Enhanced Low-Magnitude High-Frequency Vibration on Osteocytes in Regulation of MDA-MB-231 Breast Cancer Cell Migration.Cancers · 2022Article
- Breast Cancer Induced Bone Osteolysis Prediction Using Temporal Variational Autoencoders.BME frontiers · 2022Article
- Osteocytes and Cancer.Current osteoporosis reports · 2021Review
- Mechanobiology of Bone Metastatic Cancer.Current osteoporosis reports · 2021Review
Corrections and comments
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Authors and funding
7 authors.
Funding
Abstract
Osteolytic bone lesions, which develop in many metastatic breast cancer patients, impair bone integrity and lead to adverse skeletal related events that are difficult to treat and sometimes fatal. Moderate mechanical loading has been shown to suppress osteolysis in young mice with breast cancer. In this study, we aimed to investigate the dose-dependent effects of mechanical loading on protecting the integrity of adult skeletons with breast cancer. Localized tibial loading and aerobic treadmill running with three levels of varying intensity were tested in a syngeneic mammary tumor bone metastasis model. Adult C57BL/6J female mice (14-week-old, N = 88 mice) received intra-tibial injections of Py8119 triple-negative murine breast cancer cells or PBS and underwent 4 to 5 weeks of exercise or acted as sedentary/non-loaded controls. The bone structure was monitored longitudinally with weekly in vivo micro-computed tomography imaging, while the cellular responses in bone and marrow were examined using immunohistochemistry. Moderate treadmill running (16 m/min, 50 min/day, 5 days/week, and 5 weeks) and tibial loading (4.5 N, 630 με, 4 Hz, 300 cycles/day, 5 days/week, and 4 weeks) suppressed tumor-induced bone destruction, as evaluated by full-thickness perforation of tibial cortex and the volume of osteolytic lesions in the cortex. In contrast, tibial loading at higher magnitude (8 N, 1100 με) induced woven bone and accelerated bone destruction, compared with the non-loaded controls. The three exercise regimens differentially affected osteocyte apoptosis, osteocyte hypoxia, osteoclast activity, bone marrow vasculature, and tumor proliferation. In conclusion, the relationship between exercise intensity and the risk of breast cancer-induced osteolysis was found to follow a J-shaped curve in a preclinical model, suggesting the need to optimize exercise parameters in order to harness the skeletal benefits of exercise in metastatic breast cancers.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.