Did you know some types of chemotherapy can increase the risk for bone loss and fractures?

“Bone loss that occurs with cancer therapy is more rapid and severe than postmenopausal bone loss in women or normal age-related osteoporosis in men.” - Guise TA: Bone loss and fracture risk associated with cancer therapy. Oncologist 11:1121-1131, 2006

Cancer and its treatment can have profound negative effects on bone health. While there are specific cancer types that can metastasize to the bones, notably breast (70%), prostate (85%), lung (40%), and kidney (40%), chemotherapy and radiation therapy for other cancers can have a direct effect on bone health as well. Then, there are still other types, such as multiple myeloma, that are predominantly localized in the bone (95%).

With regards to the most prevalent cancers that affect bone health, about 1 in 8 men will be diagnosed with prostate cancer during their lifetime, while the average risk of a woman in the United States developing breast cancer sometime in her life is about 13%. Many of the therapies used for the treatment of breast and prostate cancers are associated with bone density loss, which in turn leads to an increased risk of fracture. While this blog will specifically address bone health with regards to breast cancer treatment, future blogs will target other common cancers such as those of the prostate and the lung.

When we specifically look at breast cancer, there are an estimated 3.1 million survivors in the United States. The 5-year survival rates after breast cancer treatment are approximately 90%. Among several other concerns regarding survivorship, bone health and prevention of fractures related to loss of bone density remains a major issue. Both the disease itself and the treatments pose specific challenges to bone health.

This is compounded by the fact that breast cancer is most prevalent in post-menopausal women, who are already at increased risk for decreased bone density due to the loss of circulating estrogen. In the general population, at least 40% of postmenopausal women will experience a fracture related to decreased bone density. In women, estrogens are critical for the maintenance of normal bone mass. At menopause, loss of ovarian follicular activity causes a significant fall in circulating levels of estrogen, which disrupts normal bone remodeling. The most rapid bone loss occurs in the first 3 years post-menopause (2–5%/year), after which bone loss slows to around 0.5–1.0% per year. A greater proportion of bone loss occurs at sites containing trabecular bone, such as the spine, than at cortical sites, such as the hip. There are two general terms used to describe bone density:

• Osteopenia means you have lower-than-normal bone density. Osteopenia isn't a disease, but it can mean that you're at higher risk of breaking a bone.
• Osteoporosis is a disease that lowers your bone density, making your bones very brittle and easily breakable.

Breast cancer therapy involves chemotherapy in most cases and the need for endocrine therapy for 5 to 10 years in most patients for prevention of recurrence. About 50 to 70% of breast cancers require the female hormone estrogen (estradiol) to grow, while other breast cancers are able to grow without estrogen. Estrogen-dependent breast cancer cells produce hormone receptors, which can be estrogen receptors (ER), progesterone receptors (PR), or both. These cancers are known as hormone-responsive. Breast cancers that are hormone-responsive are more likely to benefit from treatments that lower estrogen levels or block the actions of estrogen.

Recommended Read : Lymphedema and Breast Cancer

Following are some of the treatments used for breast cancer which can negatively affect bone health:

• Certain types of chemotherapy that cause bone loss due to both the induction of premature menopause and their direct effects on bone turnover.
• Medications known as luteinizing hormone-releasing hormone (LHRH) agonists, which affect the production of estrogen in the ovaries either temporarily or permanently. The most commonly used drug in this class is goserelin (brand name: Zoladex).
• Surgical removal of the ovaries, required for some women as part of their treatment.
• Hormonal therapy using tamoxifen, which is a selective estrogen receptor modulator (SERM) that can be used to treat both pre- and postmenopausal women with breast cancer. It blocks estrogen from binding to the estrogen receptor on breast cancer cells, so estrogen cannot promote the growth of the cancer cells. Recent data shows that tamoxifen does NOT have an appreciable negative effect on bone health. It can cause joint pain and several other side effects, however.
• Aromatase inhibitors that may be part of your treatment if you’re diagnosed with hormone-receptor-positive breast cancer after menopause. These inhibitors block the production of estrogen but can cause bone loss as a side effect. These include Arimidex (chemical name: anastrozole), Aromasin (chemical name: exemestane), and Femara (chemical name: letrozole). AIs stop the production of estrogen in your body.
• Steroid medications (such as prednisone and cortisone) that tend to both reduce the body's ability to absorb calcium and increase how fast bone is broken down.

Aromatase inhibitor (AI) is one of the well-known risk factors for osteoporosis in postmenopausal breast cancer patients.

Aromatase inhibitors are used primarily in postmenopausal women because the ovaries in premenopausal women produce too much aromatase for the inhibitors alone to block effectively. The main sources of estrogen in postmenopausal women are the adrenal glands and fat tissue, not the ovaries. If you’re postmenopausal and take tamoxifen, it can actually help build bone density. For postmenopausal women, tamoxifen’s effects on bone are similar to the effects of the estrogen you used to have in your body naturally. As a breast cancer patient, it is vital to always talk to your cancer care team about the risk of cancer recurrence versus side effects that can be temporary or permanent but manageable.

The next blog will address ways to help maintain good bone health as well as the risk factors that you need to be aware of when it comes to your risk for osteopenia or osteoporosis.