Boning Up

CURE, Winter 2010, Volume 9, Issue 4

Helping bones stay strong after cancer.

When you’re fighting cancer, you may not think about your bones. But cancer-related bone loss is one of the most common side effects of the disease, particularly for those receiving hormone therapy.

“Bone loss among cancer patients is an extremely common and highly unrecognized problem,” says Pauline Camacho, MD, associate professor at Loyola University and director of the school’s Osteoporosis and Metabolic Bone Disease Center. “In the midst of cancer therapy, the bones are usually the last thing patients and physicians think about.”

While it may seem inconsequential in the big picture, bone loss can have long-term consequences, including increased risk for fractures. The good news? Cancer specialists say there are effective ways to slow and even reverse bone loss.

Bone loss can result from a variety of factors, Camacho notes. For example, the nausea and vomiting that accompany certain types of chemotherapy is commonly addressed with powerful steroids, such as dexamethasone. If used over a long period, Camacho explains, these compounds can induce a loss of bone mass by inhibiting osteoblasts, the cells that form new bone tissue, and stimulating the production of osteoclasts, which break down bone. In addition, Camacho says, glucocorticoids can increase the loss of calcium through the urine. Chemotherapy can also cause bone loss through direct effects on the bone and also because they can cause women to experience premature menopause, which is associated with bone loss.

Women with hormone-stimulated tumors, such as breast and uterine cancers, are especially at risk of osteoporosis, says Stephanie Hines, MD, assistant professor of medicine with the Mayo Clinic in Jacksonville, Florida. The reason: treatments such as aromatase inhibitors can accelerate bone loss by inhibiting the production of estrogen, a hormone that can feed tumors but also maintain bone mineral density, Hines explains. Similarly, bone loss can occur in men with prostate cancer—another hormone-stimulated disease—through the use of androgen-inhibiting therapies, which sometimes results in a condition called hypogonadism, in which hormone levels decrease in the sex glands.

In the midst of cancer therapy, the bones are usually the last thing patients and physicians think about.

In many cases of bone loss, cancer treatment may not be the sole culprit—often there are secondary causes at work. In a study reported in the Journal of Clinical Oncology, Camacho and colleagues performed screening DEXA scans, which measure bone density, on 64 otherwise healthy women with early-stage breast cancer. They found that a significant percentage of the subjects had either osteopenia (mild bone loss) or osteoporosis (severe bone loss).

“We found a very high rate of vitamin D deficiency,” Camacho reports. “We also found a high rate of a condition called idiopathic hypercalciuria (a condition that causes people to lose too much calcium through urine) and a pretty high proportion of patients with primary hyperparathyroidism. More than 50 percent of the patients had some condition that affected their bones.” This is significant, Camacho adds, because many of the women in the study were receiving potentially bone-affecting aromatase inhibitors or were about to begin.

According to Gralow, bone loss is typically asymptomatic. In fact, most patients don’t realize they are osteoporotic until they experience a fracture. “It’s like high blood pressure,” Gralow notes. “Most people, unless it’s really severe, don’t feel any symptoms.”

Among them is Marilyn Scher, 65, of New York City, whose case is a textbook example of treatment-related bone loss. A multiple-cancer survivor, Scher was treated for melanoma in 1973 and ovarian cancer in 1996. She underwent a lumpectomy for breast cancer in 2003 and was diagnosed with cancer in the same breast in May 2007, for which she had a mastectomy. She has been taking the estrogen-blocking drug Femara (letrozole) since then.

A routine bone density scan revealed that Scher has osteoporosis and osteopenia, primarily in her hips and spine. The bone loss is a likely side effect of her cancer treatment, but Scher notes that there may be other contributing factors, including the use of a medication for gastric reflux, which is known to exacerbate osteoporosis, and suspected hyperparathyroidism. “I’m complicated,” Scher says.

She has been receiving the osteoporosis-fighting drug Zometa (zoledronic acid), in addition to calcium and vitamin D supplementation, to counteract her bone loss, but she says that it has been an uphill fight. She is now receiving Zometa by infusion four times a year (most patients receive it annually), but her bone loss continues to worsen. “I’ve been a puzzle to my physicians,” Scher says, “because my bone loss is not getting better.”

[Bone loss] is like high blood pressure. Most people, unless it’s really severe, don’t feel any symptoms.

According to Gralow, treatment options for bone loss fall into two general classes. The largest is the anti-resorptive family of drugs, specifically bisphosphonates, such as Actonel (risedronate), Fosamax (alendronate), Zometa, Reclast (another type of zoledronic acid) and Bondronat (ibandronate). These compounds don’t speed up bone formation, Gralow explains; instead, they slow bone breakdown so the body can build more bone naturally.

The second class of treatment options is anabolic, or bone-building, drugs. The only compound in that family to date is Forteo (teriparatide), a parathyroid hormone. According to Gralow, this drug is much less commonly prescribed for cancer patients than anti-resorptive drugs because of a lack of safety data for that population.

Bones are not static. They are constantly undergoing some break down and some build-up. This process makes bones strong, says Julie Gralow, MD, professor of medicine at the University of Washington in Seattle and director of breast oncology at the Seattle Cancer Care Alliance. “But if you have estrogen loss, you’re not absorbing vitamin D as well,” Gralow says, “and what ends up happening is the osteoclasts predominate over the osteoblasts.”

A newly added weapon in the arsenal against bone loss is Xgeva (denosumab), which inhibits the production of bone-removing osteoclasts. Xgeva was approved in November for patients with solid tumors whose cancer has moved to the bone. These drugs are very convenient, Camacho says, because they are given via an injection every six months.

Cancer patients can help fight bone loss by boosting their intake of bone-strengthening calcium, reports Hines. Vitamin D should always be taken in conjunction with calcium, she adds, because it greatly improves calcium absorption. But don’t assume that if a little calcium is good, a megadose is even better. According to Gralow, calcium can overwhelm the digestive tract, so three 500-mg doses a day will achieve greater absorption than a single 1,500-mg dose.

It’s also important that cancer patients receive a DEXA scan to determine the extent of their bone loss, says Camacho. The technology uses X-rays to calculate the amount of calcium in a square area of bone, a figure known as a T-score. A T-score of —2.5 or lower defines osteoporosis, while –1 to –2.4 indicates osteopenia.

Depending on the type of cancer, bone loss may be an inevitable consequence of treatment. But that doesn’t mean you have to live with it; discuss the issue with your physician and oncologist at the beginning of your treatment and throughout. Scher encourages patients to, “learn as much as you can, and maintain a positive attitude.”