Androgen-deprivation therapy (ADT), a common treatment for advanced prostate cancer, can lead to severe bone loss in some men. But experts now say that better risk assessment and early intervention with drugs or lifestyle changes can alleviate the problem.
The conclusions emerged from a meeting, convened in 2001 by Dr. Tia Higano, a medical oncologist at the University of Washington and the Seattle Cancer Care Alliance, to assess treatments for bone loss in men. Higano and colleagues reported this information, including guidelines to improve diagnosis and therapy, in the March 1 issue of Cancer.
The paper is based on an extensive review of published scientific articles about the diagnosis and medical care of men suffering from osteoporosis, the medical term for decreased bone mass, and related conditions. Based on their survey, the authors of the study, led by Dr. Terrance Diamond of the University of South Wales in Sydney, Australia, devised a risk-assessment tool to help doctors determine which prostate-cancer patients would benefit most from therapy to minimize bone loss.
Higano said that a primary motivation for the study was to raise awareness of the problem, which many believe is common among men who receive ADT. The therapy works by interfering with the male hormones that spur the growth of prostate tumors and is often prescribed for men whose cancer has spread beyond the prostate.
ADT and 'male menopause'
Although ADT can reduce tumor growth and improve survival, doctors have been increasingly concerned about the negative effects the drugs can have on the skeleton. While reducing stimulation of prostate-tumor cells, ADT also results in "male menopause," causing changes to bone-remodeling cells. The problem can be especially severe in older men, who are already at risk for osteoporosis or may have the condition even before they are diagnosed with cancer. Bone loss can lead to fractures and associated complications.
"We don't know how widespread this problem is, because no large prospective studies have addressed it," Higano said. "But based on our own prospective data reported at the 1999 American Society of Clinical Oncology and subsequent studies, between 10 percent and 40 percent of men already have low bone mineral density even before they start androgen-deprivation therapy."
Drugs known as bisphosphonates, which strengthen bones and alleviate pain, are commonly prescribed for those with osteoporosis or cancer patients whose disease has spread to the bone. Higano said that preventive measures will likely slow bone loss and recommends counseling about behaviors that can minimize osteoporosis, such as maintaining adequate calcium and vitamin D intake and engaging in both aerobic and resistance or strength-building exercises.
Systematic diagnosis, treatment
"We're hoping that these guidelines will offer a systematic approach for diagnosing and treating the problem," she said. "Rather than immediately prescribing prophylactic bisphosponates for all patients on ADT, doctors can use the risk-assessment algorithm to evaluate baseline and follow-up bone-mineral density results and to intervene when appropriate with bisphosphonate therapy."
For example, a man who has low body weight and is of slight build is of greater risk for osteoporosis than a heavier stocky man of the same age. Skeletal integrity can be measured with bone-mineral density scans, a technique that uses low-dose X-rays to examine bone density in critical areas, such as the hip or spine. Higano has recently purchased a DEXA (dual energy X-ray absorptiometry) scanner, an instrument that provides rapid and accurate bone-density measurements. The instrument soon will enable Alliance physicians to conduct bone-density analyses for all cancer patients who are at risk of bone loss due to hormone or steroid use.
In the Cancer review, the authors found that men with prostate cancer treated with ADT have a substantial risk for significant bone loss. Bone-mineral density scans of the hip and spine show that men treated with ADT have 1.8 percent to 6.5 percent bone loss from the hip and 2 to 8 percent bone loss from the lumbar (mid-back) spine after only 9-12 months of therapy. This compares with the expected loss of 0.5 percent per year in men who are not receiving ADT. These losses continue over time but appear to slow with intermittent ADT, an approach that Higano has studied extensively.
Death and complications resulting from hip fractures are reported to be significantly higher in men than in women. While currently no randomized trials assessing the benefits of bisphosphonates in fracture prevention exist, studies have demonstrated the positive effects of these agents on bone mass in men treated with ADT. Now that more men without prostate cancer metastases are being treated with ADT and are expected to live for many years, it is even more crucial for bone mass to be monitored, Higano said.
She and her colleagues hope their analysis will be disseminated among the broad variety of doctors who treat prostate-cancer patients, including internists and urologists as well as medical oncologists.
"Many doctors are unsure about what to do with the information that is out there on the topic," Higano said. "We're hoping that this algorithm will change treatment in a logical way."
