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From OncoLog, March 2010, Vol. 55, No. 3

Preventing Bone Loss and Fractures in Cancer Patients

By Joe Munch

Photo: Bone density scan
“In some cancer patients, even a sneeze or cough could cause a spinal fracture.”

Dr. Mimi Hu

Cancer patients experience many sequelae during and after treatment for their disease. With many patients now surviving decades after treatment has ceased, late-stage sequelae and their effects on overall health and quality of life have become important concerns. High among these concerns is bone loss.

Mimi Hu, M.D., an assistant professor in the Department of Endocrine Neoplasia and Hormonal Disorders, is working with her colleagues at MD Anderson Cancer Center to identify patients at risk of developing low bone density (osteopenia) and osteoporosis, which may lead to debilitating fractures that cause severe pain, complicate care, or decrease quality of life.

“Ultimately, what is clinically relevant to these patients is whether they will develop fractures,” Dr. Hu said. “And when we talk about fractures, we’re not talking about high-impact fractures such as those that can occur in a motor vehicle accident. We’re concerned about fractures caused by very low or minimal trauma. In these patients, even a sneeze or cough could cause a spinal fracture.”

Causes of bone loss in cancer patients

Several factors contribute to bone loss in cancer patients. Patients may have underlying conditions such as vitamin D deficiency or abnormal calcium metabolism due to hyperparathyroidism, or they may have malignancies such as multiple myeloma and leukemia that actually cause bone loss. In some patients, poor diet owing to treatment intolerance can cause diarrhea, leading to poor calcium and vitamin D absorption.

More often, loss of bone mass is due to cancer treatments themselves. Radiation therapy can break down bone-building cells, making bones susceptible to insufficiency fractures—a major concern in patients with gynecologic cancers who receive radiation to the pelvis. Steroid therapy, commonly given to patients with nonsolid cancers such as leukemia and lymphoma, stimulates osteoclasts, cells that destroy bone tissue. Various chemotherapies can also cause bone loss. Cyclophosphamide (a component of Revimmune, Cytoxan, Neosar, and other drugs) suppresses bone marrow growth, and taxane-based chemotherapies such as paclitaxel and docetaxel can induce early menopause in addition to stimulating osteoclasts.

“Early induction of menopause is a risk factor for bone loss, especially in breast cancer patients,” Dr. Hu said. “Within 5–10 years after natural menopause, women can lose approximately 2% of their bone mass every year. But with chemotherapy-induced early menopause, patients can lose 3%–8% per year, and that’s a significant amount.”

Medications for Bone Loss

In addition to making lifestyle changes—increasing vitamin D and calcium intake, for example, or performing weight-bearing exercises regularly—cancer patients may be able to take any of a number of drugs to curb or prevent bone loss.

  • Salmon synthetic calcitonin (Calcimar, Miacalcin, others), a hormone that suppresses osteoclast activity, was the first drug approved for osteoporosis and was standard therapy for bone loss 10 years ago. Calcitonin is given as a nasal spray, and a typical side effect is mucous membrane irritation from constant use. Calcitonin may also decrease bone-related pain from arthritis or fractures.
  • Bisphosphonates such as alendronate (Fosamax), risedronate (Actonel), ibandronate (Boniva), and zoledronic acid (Zometa), which cause osteoclast death, are considered initial therapy for bone loss and can be given as pills, injections, or infusions. Side effects include reflux disease, esophageal erosion, increased kidney dysfunction in patients with kidney disease, and muscle aches, especially in patients with an underlying vitamin D deficiency.
  • Teriparatide (Forteo), a synthetic form of parathyroid hormone that is self-injected once daily, stimulates bone growth. Currently, teriparatide is approved for only 2 years of use. It is contraindicated in patients with underlying, ongoing skeletal malignancy, patients who have received external or implant radiation therapy, and patients with Paget’s disease of the bone.
  • Raloxifene (Evista), a selective estrogen receptor inhibitor, has been found to increase bone mass in postmenopausal women and be at least as effective as tamoxifen in reducing breast cancer recurrence in patients at high risk of recurrence. However, raloxifene can increase the risk of a cerebrovascular event in patients with a history of stroke and in patients who smoke.

Breast cancer patients and prostate cancer patients, who comprise the majority of cancer patients, are most affected by bone loss and its repercussions.

In prostate cancer patients, efforts are often made to shrink the cancer or cause it to grow more slowly by reducing testosterone levels through orchiectomy—the surgical removal of one or both testicles—or hormonal ablative therapy with chemicals such as leuprolide (Leupron) or bicalutamide (Casodex). However, Dr. Hu said, “We’re finding that estrogen levels, as well as testosterone levels, are important for bone health in men. There are more and more data to support that estrogen reduction is actually the more important aspect in osteoporosis in men.”

In breast cancer patients, selective aromatase inhibitors such as anastrozole (Arimidex), letrozole (Femara), and exemestane (Aromasin), which inhibit the enzyme that synthesizes estrogen, are used to lower patients’ estrogen levels and thus slow tumor growth. But while lower estrogen levels may impede tumor growth, they also impede bone growth.

“Aromatase inhibitors are very important in further reducing estrogen levels, especially in patients who are already postmenopausal, and that further reduction of estrogen will significantly inhibit bone formation and increase bone resorption,” Dr. Hu said.

Preventive treatment

In addition to basic preventive treatment—getting plenty of calcium and vitamin D and adhering to a regimen of weight-bearing exercise—several drugs have emerged in the past decade that can be used to curb bone loss in cancer patients. Ten years ago, salmon synthetic calcitonin (Calcimar, Miacalcin, others), a hormone that suppresses osteoclast activity, was standard therapy for bone loss. Although calcitonin is effective in reducing bone loss, the drug is not as effective as other medicines available today. Among these newer drugs are bisphosphonates such as alendronate (Fosamax), risedronate (Actonel), ibandronate (Boniva), and zoledronic acid (Zometa), which are considered initial therapy for bone loss.

“Bisphosphonates get taken up by osteoclasts and cause cell death,” Dr. Hu said. “By causing osteoclasts to die, bone degradation is reduced, which can then decrease fracture risk.”

In contrast to bisphosphonates, teriparatide (Forteo), a synthetic form of parathyroid hormone, can stimulate bone growth. The drug is approved for up to 2 years of use. However, because teriparatide has been observed to cause osteosarcoma in rat models, the drug is contraindicated in patients who have an increased baseline risk for osteosarcoma, including patients with Paget’s disease of the bone or previous external beam or implant radiation involving the skeleton. “We must be cautious in the use of this drug in our cancer survivors given the extent of radiation therapy in this population and also the possibility of occult malignant cells.”

Raloxifene (Evista), which is in the same drug class as tamoxifen, has been found to increase bone mass in postmenopausal women. As an added benefit, raloxifene has also been found to be at least as effective as tamoxifen in reducing breast cancer recurrence in high-risk patients.

However, even as medications become more effective in preventing or curbing bone loss, the guidelines for their use must be constantly reconsidered and revised.

“Today, we must weigh the risks and benefits of therapy for bone loss for each individual patient,” Dr. Hu said. “The questions I constantly face are: when is the right time to prescribe these drugs for bone loss, will I improve my patient’s overall health, will therapy decrease longterm fracture risk, and how long should I treat my patient with these therapies? The first thing a physician needs to do is to recognize that patients with cancer are at risk for bone loss and then to consider personalized therapy in the context of their overall cancer care.”

Bone Health Center to Address Cancer Patients’ Needs

Citing an increasing number of cancer patients with bone loss–related health issues, clinicians are establishing a bone health center at MD Anderson.

As envisioned, the center will use a multidisciplinary approach, employing the knowledge of health care providers including endocrinologists, oncologists, rheumatologists, radiologists, pain control specialists, nutritionists, and surgeons to educate and provide care for patients.

Patients referred to the clinic can likely expect to undergo bone density scans (dual-energy x-ray absorptiometry) if they have not done so previously, blood testing for vitamin D deficiency and causes of abnormal calcium metabolism (e.g., hyperparathyroidism), urine collection to test for calcium loss, radiography to check for fractures, and testing for other causes of bone loss. Patients’ family history, body habitus, general health, and vitamin D and calcium intake will also be evaluated. Patients will fill out questionnaires assessing their bone health and risk factors for bone loss and visit with health care providers to discuss risks of further bone loss. If medical therapy is indicated, health care providers will discuss options.

The center will provide learning aids, articles, and online materials about bone health to educate patients and their families. Survivorship issues will also be addressed.

Although cancer patients with bone loss have received care at MD Anderson for decades, the bone health center will facilitate the treatment process. “Patients will have convenient access to a whole team of specialists working in a collaborative manner,” said Lea Tatar, a program director in the Department of Endocrine Neoplasia and Hormonal Disorders who is helping to develop the center. “Not only will they receive comprehensive care, but their care will be delivered in a seamless manner. Moreover, patients will have the assurance of knowing that their care is being tailored for their individual needs.”

For more information, please contact Dr. Hu at 713-792-2841.

Other articles in OncoLog, March 2010 issue:

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