Osteoporosis in Breast Cancer Survivors


Breast cancer is of special interest here because it disproportionately affects women, as does osteoporosis.  Indeed, breast cancer is one of the most common types of cancer today, and although it has a relatively good survival rate (compared to other forms of cancer), survivors find their lives changed as a consequence of their illness.  That includes an increased risk for bone fracture.  Breast cancer patients and survivors are usually given drugs (aromatase inhibitors) to suppress production of estrogen in the body (which are thought to promote the cancer).  Some patients have surgery or chemotherapy that damages the ovaries and estrogen production.

Women who undergo treatment before menopause tend to enter menopause earlier and that lowers their estrogen levels.

Lower estrogen levels are a risk factor for osteoporosis.  Some chemotherapy drugs directly affect bones as a side effect.  Radiation therapy can also increase the risk of bone fracture, especially in those who had osteoporosis before the cancer onset.

There is also some evidence that breast cancer increases the production of osteoclasts – the cells that cause breakdown of bone material in normal bone physiology.  This influence of the cancer outside its home organ upsets the homeostasis of bone density and contributes to weakness in the bone.  The mechanism for this is a biochemical cascade that turns into a vicious cycle.  The malignant cells parathyroid hormone-related protein (PTH-RP), which prompts increased production of the rank ligand (RANKL) protein in the bone tissue.  This also causes a reduction in levels of osteoprotegerin, a key factor in bone mineralization homeostasis that increases bone density.  The high levels of RANKL also increase activity of the osteoclasts.  The osteoclasts release growth factor-ß which signal the malignant cells to produce more PTH-RP and the cycle is pushed forward. 

In advanced breast cancer, the disease often metastasizes to the bone.  That leads to bone health problems that can have similarities to osteoporosis, such as frequent fractures and high calcium levels in the bloodstream.  Treatment options are bisphosphonates and the monoclonal antibody drug denosumab, both of which are employed for osteoporosis.  Doctors monitor kidney function in these patients.

The effect of the widely used osteoporosis drug class called bisphosphonates is not clear although these drugs appear somewhat beneficial in people with breast cancer.  There have long been thoughts that the drug may contribute to a risk of esophageal cancer – irritation of the esophagus is certainly a side effect.

There is also some evidence that bisphosphonates given to breast cancer patients earlier in the cancer may enhance survival rates.   Zoledronic acid was employed in a study.  The reasons are unclear, but the bisphosphonate appears to reduce the chances of the cancer moving to the skeletal system.

Some of the broad class of drugs called selective estrogren receptor modulators are used to treat osteoporosis. These compounds stimulate or inhibit estrogen receptors in the body and are used to treat and prevent gynecological cancers. Some of them also increase the chances of cancer formation. The SERMs used for osteoporosis treatment are selected to build bone, and they somewhat simulate estrogen in some ways. Raloxifene, first used for breast cancer, is now also used to stop osteoporosis.

Other forms of cancer and osteoporosis

The drug Forteo (teriparatide) has been shown to increase the odds of bone cancer in laboratory animals.  The authorities figure the risk is low enough that they approved the drug for human use, although it is generally not given to those with a history of osteosarcoma. Men who have prostate cancer and get hormone therapy to prevent it from coming back are at high risk for osteoporosis, too.

Calcitonin seems to have an effect on prostate gland growth and may be considered a risk factor for cancer of the prostate. Calcitonin is used as a marker for a type of thyroid cancer called Medullary cancer although that is because calcitonin is produced in the thryoid.

Treatment of other forms of cancer can adversely affect bone health, too.  Chemotherapy drugs can directly harm bones, weight loss common during treatment can increase the risk of osteoporosis, decreased exercise levels, and an increased tendency to fall (due to chemobrain or general weakness) all are risks to the skeletal system.

Depending on the particulars of the patient and disease, the normal preventative measures against osteoporosis may be employed: reduce alcohol intake, quitting smoking, weight-bearing exercises.  Because cancer patients are often elderly, they are at increased risk for osteoporosis and tend to be at poorer health aside from the cancer.

Denosamub, the relatively new and little used osteoporosis drug, has been found to hava an anti-tumor effect. In a test of people with a certain type of bone cancer, the denosamub reduced or eliminated tumors. It also appears to have reduced the number of tumor stromal cells and replaced them with boney material. This was a small test, so more research is required.

 

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