Preventing Bone Loss and Fractures in Cancer Patients
By Joe Munch
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.”
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.
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.”
For more information, please contact Dr. Hu at 713-792-2841.
Other articles in OncoLog, March 2010 issue: