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No bones about it: Stay aware of risks from targeted treatments

By Mary Brolley

Remarkable improvements in cancer treatments have allowed patients — even those with metastatic disease — to live longer.

New targeted therapies like aromatase inhibitors and androgen deprivation agents are highly effective. Often used as adjuvant measures (to prevent recurrence), they’ve improved outcomes for breast and prostate cancer patients and generally have few side effects.

But one of those side effects worries Beatrice Edwards, M.D., associate professor in General Internal Medicine.

One of MD Anderson’s two geriatricians, Edwards specializes in the care of patients in active treatment who are 65 and older.

An expert in bone health, Edwards says these therapies may increase patients’ risk of developing osteoporosis. This condition makes people more susceptible to serious fractures of the hip, spine and axial areas (wrist, ankle, etc.).

A troubling trend

Beatrice Edwards, M.D.

Edwards first noticed the problem when she was working at the Bone Health Center and the Lurie Comprehensive Cancer Center at Northwestern Memorial Hospital in Chicago.

She saw a small group of women in their 50s who had suffered bone fractures (hip or vertebral fractures) after breast cancer treatment. She knew that most fractures of this type happen much later in a person’s life.

Each of the women had been treated with chemotherapy and some with aromatase inhibitors, which work by blocking estrogen production.

In a 2011 paper in Clinical Cancer Research, Edwards and her colleagues detailed their findings about the serious adverse drug reactions caused by aromatase inhibitors.

Her recent work, presented at the ASCO Breast Cancer Symposium in September 2013, reveals that women with breast cancer may suffer fractures at relatively “normal” bone mineral densities.

Further research is needed to assess new imaging technologies that may identify those women at highest risk of fractures, she says.

The costs of osteoporosis

The National Institutes of Health defines osteoporosis as “a systematic skeletal disease characterized by low bone mass and micro-architectural deterioration of bone tissue leading to enhanced bone fragility and a consequent increase in fracture risk.”

Osteoporotic fractures are far more common than heart attacks, breast cancer and strokes. And fractures — especially hip fractures — are a major cause of disability.

One year after a hip fracture, 80% of patients cannot carry out at least one independent activity of daily living, like meal preparation, heavy housekeeping, climbing stairs, shopping, etc.

Hip fractures are a major cause of nursing home admissions, and the mortality rate one year after the fracture is 20% to 30%.

Why some targeted therapies can harm bones

Agents like aromatase inhibitors and androgen deprivation shrink or kill tumors by blocking production of estrogen. But circulating estrogen is crucial to bone health.

With tamoxifen, the issue is more complicated. A selective estrogen receptor modulator (or SERM), it has different effects on a woman’s bones depending on her menopausal status.

A 2006 study in the Journal of Clinical Oncology found that tamoxifen was associated with bone loss in premenopausal patients, but not in those who are postmenopausal. In fact, tamoxifen reduced the risk of osteoporotic fractures in these women.

So, age and menopausal status are factors in whether these therapies damage patients’ bone mineral density.

And because some types of chemotherapy induce premature menopause, women may face these problems at much younger ages than their peers.

Edwards says that though they’re quite effective, special care and monitoring are crucial when these targeted therapies are chosen as part of a treatment plan.

How to protect your bones

Though many factors that influence a person’s risk for developing osteoporosis can’t be changed — heredity, gender, age and menopausal status, for example — diet and exercise interventions may reduce this risk from 15% to 30%.  

Edwards advises her patients to get checked for nutritional and vitamin deficiencies that may worsen the bone loss.

And medications like bisphosphonates and denosumab slow or stop the natural process of bone loss.

Denosumab (Prolia®) has recently been approved for prevention of cancer treatment-induced bone loss, and bisphosphonates such as zoledronic acid (Reclast®), alendronate (Fosamax®) or risedronate (Actonel®) are also effective.

Exercise also plays a crucial role, Edwards says.

She encourages her patients to exercise daily, making sure to include both weight-bearing and balance-improving elements to their routine.

The bottom line is that, as we age, bone health can make the difference between independence and disability.

And those who’ve faced cancer need to be especially vigilant.

“The changes to your bones that occur with aging don’t begin when you’re 70, they begin at 50,” Edwards says. “And cancer ages you before your time.”

She believes that more research is needed to develop tools to measure patients’ bone health before they begin cancer treatment, so they can receive guidance about the best ways to protect their bones.

Expert recommendations

  • Eat more protein and calcium-rich foods.
  • Ask your physician to check you for vitamin deficiencies.
  • Aim for 30 minutes of exercise a day. Include both weight-bearing and 
balance-improving (such as yoga or 
tai chi) exercises.
  • Stop smoking and limit alcohol 
consumption.

© 2014 The University of Texas MD Anderson Cancer Center