Denosumab may expand treatment options.
By Kari Bohlke, ScD
Bone loss is a concern for many of us. Osteoporosis—a disease characterized by bone fragility and low bone mass—affects an estimated 10 million people in the United States and is responsible for more than 1.5 million fractures each year. These fractures commonly involve the hip, spine, and wrist but may involve other sites as well.
Bone loss accelerates as we age (with particularly rapid loss in women after menopause), but it can also result from use of certain medications, including some that are used for cancer treatment. In women with breast cancer, use of the hormonal therapy drugs known as aromatase inhibitors reduces bone density. Similarly, in men with prostate cancer, androgen-deprivation therapy contributes to bone loss and fracture risk.
Drugs that may be used for the prevention or treatment of osteoporosis include bisphosphonates (such as Fosamax® [alendronate], Actonel® [risedronate], Boniva® [ibandronate], and Reclast® [zoledronic acid]), calcitonin, estrogen, Evista® (raloxifene), and Forteo® (teriparatide). These drugs may soon by joined by another, however, which would expand treatment options for patients.
Denosumab, which is still being reviewed by the U.S. Food and Drug Administration, has a different mechanism of action from other currently available bone drugs. It targets a protein known as the RANK ligand, which plays an essential role in the formation, function, and survival of osteoclasts—the cells that break down bone. By inhibiting this protein, denosumab decreases bone resorption and increases bone mass and bone strength. The drug is given as a subcutaneous (under-the-skin) injection every six months.
Reports from several large studies suggest that denosumab may provide benefits to patients with a variety of conditions, including postmenopausal osteoporosis, bone loss from cancer treatment, and bone metastases (cancer that has spread to the bone from another site in the body).
- Postmenopausal osteoporosis. In a study of more than 7,800 postmenopausal women with osteoporosis, those who received denosumab for three years were 68 percent less likely to suffer a vertebral fracture and 40 percent less likely to suffer a hip fracture than women who received placebo. Women who received denosumab experienced a 9.2 percent relative increase in bone mineral density at the lumbar spine and 6.0 percent relative increase at the total hip compared with placebo.
- Prostate cancer treated with androgen-deprivation therapy (ADT). In a study of 1,468 men undergoing ADT for nonmetastatic prostate cancer, those who received denosumab were 62 percent less likely to develop a new vertebral fracture than those who received a placebo. Furthermore, by 24 months men in the denosumab group had a 5.6 percent increase in bone density at the lumbar spine compared with a 1 percent loss in bone density among men in the placebo group. Men receiving denosumab also experienced increases in bone density at nonvertebral sites such as the hip and the wrist.
- Breast cancer treated with aromatase inhibitors. The effects of denosumab among women treated with an aromatase inhibitor were evaluated in a study of 252 women with nonmetastatic, hormone receptor–positive breast cancer. At the start of the study, all study participants had evidence of bone loss but none had osteoporosis. Compared with women in the placebo group, lumbar spine bone density among women in the denosumab group was 5.5 percent higher at 12 months of follow-up and 7.6 percent higher at 24 months of follow-up. Women treated with denosumab also had higher total body bone density and higher bone density at the hip, femoral neck, and radius.
- Bone metastases (cancer that has spread to the bone). Denosumab has been directly compared with the bisphosphonate drug Zometa in studies of cancer patients with bone metastases. These studies assessed the occurrence of bone complications such as fracture, radiation to the bone, surgery to the bone, or spinal cord compression. Among breast cancer patients, denosumab was more effective than Zometa at reducing the risk of bone complications. And among patients with bone metastases from cancers other than breast cancer or prostate cancer, denosumab was as effective as Zometa at reducing the risk of bone complications.
One potential safety issue that has arisen in studies of postmenopausal osteoporosis is an increased risk of serious infections such as cellulitis (bacterial infection of the skin). Although rare, these infections were more common in women treated with denosumab than in women treated with placebo.4 Safety information continues to be collected and monitored.
The good news for patients is that bone health is increasingly receiving the attention it deserves, and options for the prevention and the treatment of bone loss are expanding. These options include regular physical activity and a healthy diet as well as a range of medications that increase bone density and reduce the risk of fracture. Preservation of bone health is important to general wellness before, during, and after cancer treatment.
Keeping Your Bones Strong and Healthy
- Get the daily recommended amounts of calcium and vitamin D.
- Engage in regular weight-bearing and muscle-strengthening exercise.
- Avoid smoking and excessive alcohol.
- Talk to your healthcare provider about bone health.
- Have a bone-density test and take medication when appropriate.
. Osteoporosis Overview. National Institute of Arthritis and Musculoskeletal and Skin Diseases Web site. Available at: http://www.niams.nih.gov/Health_Info/Bone/Osteoporosis/default.asp. Accessed October 3, 2009.
. Ellis GK, Bone HG, Chlebowski R, et al. Randomized trial of denosumab in patients receiving adjuvant aromatase inhibitors for nonmetastatic breast cancer. Journal of Clinical Oncology. 2008;26(3):4875-82.
. Denosumab demonstrates superiority over Zometa in pivotal phase 3 head-to-head trial in breast cancer patients with bone metastases [news release]. Amgen Web site. Available at: http://wwwext.amgen.com/media/media_pr_detail.jsp?year=2009&releaseID=1305355. Accessed October 3, 2009.
. Amgen announces positive top-line results for denosumab in trial for delay of skeletal related events in bone metastases patients compared to Zometa® [news release]. Amgen Web site. Available at: http://wwwext.amgen.com/media/media_pr_detail.jsp?year=2009&releaseID=1316081. Accessed October 3, 2009.
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