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Weight bearing exercise may reduce bone mets.

Weight Bearing Exercise May Help Curb Metastatic Bone Tumors

Human bone is like a bank vault holding a fortune in gold – except the “gold” is actually precious growth factors that pay a vital role in bone health. These growth factors are the target of greedy cancer cells that have broken away from their primary tumor and spread to bone. The cancer cells need those growth factors in order to develop in the bone, but they must compete with healthy bone tissues that also need those factors.

Healthy bones exist in a state of dynamic internal regeneration. One stage of the regeneration occurs when older bone tissue is resorbed while the other stage involves depositing new tissue. This cycle maintains normal bone density and strength, and it relies upon the growth factors stores in bone tissue. When cancer cells metastasize to the bone, they being “stealing the gold” by using genetic messengers to disrupt that dynamic balance. Scientists theorize that metastatic tumor cells harness a messenger called Runx2i to instruct bone cells to produce too many proteins. When this occurs, the bone breaks down without adding new deposits, and its growth factors become available for the greedy tumor cells. At the same time, the bone is structurally weekend. Thus, the bone becomes fragile while the tumor profits.

For many non-cancerous diseases that deteriorate bones, such as osteoporosis in postmenopausal women, a standard of care is to prescribe weight bearing exercise. This is called loading the bone, and if done on a frequent, regular basis, it naturally induces the formation of greater bone mass for both healthy and unhealthy bones. Researchers at Cornell University had a hypothesis that loading the bone could offset the destructive action of the bone mets. They wanted to test it out, and if possible explain the biochemical processes involved.

Using laboratory mice, they conducted a 2-part controlled experiment. One part was an in vivo (living animal) study involving breast cancer cells implanted into a leg bone (tibia) of each mouse; non-cancer mice were used as controls. Once the tumor cells began to grow, mechanical compression (load) was applied to the leg bone of each mouse 5 times per week for either 2 or 6 weeks (the mice were anesthetized during compression). The results were then analyzed using both CT scans and ultimately pathology.

The other part tested the effects of compression on the cancer cells themselves. “They injected tumor cells into a porous scaffold that looks like an aspirin pill, then loaded [put weight on] the cells by using a piston to squeeze the scaffold. They examined how different genes characteristic of tumor cells were expressed as the loading occurred.”ii

Here’s what they found: The in vivo mouse experiment demonstrated that loading the leg bones kept the tumor from growing as well as increased the bone mass, whereas doing nothing allowed the tumor to proliferate and the bone to deteriorate. The second part of the experiment allowed the researchers to isolate Runx2 as the “culprit” genetic messenger, and exclude others.

This is a remarkable study with a dual take-away:

  1. For patients with bone mets, weight bearing exercise focused on the bone(s) containing the tumors is a non-surgical, non-radiation, non-chemotherapy way to strengthen osteolytic bone damage (deterioration) and build new bone mass. This does not replace medical intervention, but would likely support the action of other therapies.
  2. Understanding the mechanism by which tumor cells use genetic messengers can lead to the development of new bone mets therapies that act by repressing those messengers.

More study is needed in both areas. While the application of exercise is promising, bone mets patients should not begin any type of exercise without the knowledge, permission and supervision of their oncology team. It can be hard to wait for human clinical trials to study the effects of loading bones with metastatic tumors, but carefully designed and monitored studies are occurring to test the feasibility, safety and effectiveness of weight bearing exercise for osteolytic bone mets. There is another type of metastatic bone tumor called sclerotic tumors (bones become overly dense, hard and brittle) that is also undergoing weight bearing testing since the results with osteolytic tumors are optimistic.iii

So take heart, weight bearing exercise may yet prove to be nature’s own defense to help guard the “gold” from the tumor thieves.

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iLynch ME, Brooks D, Mohanan S, Lee MJ et al. In vivo tibial compression decreases osteolysis and tumor formation in a human metastatic breast cancer model. J Bone Miner Res. 2013 Nov;28(11):2357-67.
iiJu, Anne. “Exercise could reduce bone tumor growth.” Cornell Chronicle, June 1, 2017. http://news.cornell.edu/stories/2013/05/exercise-could-reduce-bone-tumor-growth
iiiHart NH, Newton RU, Spry NA, Taafe DR et al. Can exercise suppress tumour growth in advanced prostate cancer patients with sclerotic bone metastases? A randomized, controlled study protocol examining feasibility, safety and efficacy. BMJ Open. 2017 May 30;7(5):e014458.

CATEGORY:
Bone mets