More than two million American men alive today have been diagnosed with prostate cancer at some point in time. After skin cancer, prostate cancer is the most common cancer in men. The number of men battling prostate cancer is staggering. According to the latest statistics from the American Cancer Society, an estimated 217,730 new cases were diagnosed in 2010. The good news hidden here is that the number of prostate cancer deaths continues to decline. They report a nearly 100 percent, five-year chance of survival for prostate cancer found in the prostate only or spread from the prostate to nearby areas.
This means that for most men prostate cancer is a chronic disease. Since men with prostate cancer are living longer, they may be receiving treatment for longer periods of time. It is now recognized that some therapies may increase bone loss and the risk of fractures. As a result, doctors are more attuned to the importance of bone health in their patients treated for prostate cancer.
Why Are Men with Prostate Cancer at Risk for Bone Loss and Fracture?
In the same way that hormonal (antiestrogen) therapy for women with breast cancer increases the risk of bone loss and fracture, hormonal therapy for prostate cancer boosts the risk of bone loss and fracture in men. In prostate cancer treatment, the hormones being suppressed or blocked are the male hormones, called androgens, including testosterone. You may see the term “androgen deprivation therapy” or ADT. That abbreviation always makes me think of the home security company. You can think of the treatment as a way to keep the body secure and safe from the growth of prostate cancer cells.
Initially, androgen deprivation therapy was used to treat advanced prostate cancer. Now it has much wider use in earlier stages, such as in men with prostate-specific antigen (PSA) levels that are creeping up after their initial cancer therapy. It is estimated that one-third of the two million prostate cancer survivors in the US are on hormonal therapy. Unfortunately, this treatment comes with some difficult side effects. Recent reports of increased heart disease risk and death may change how commonly these drugs are prescribed.
With hormonal therapy, blood levels of testosterone drop by more than 95 percent and estrogen decreases by about 80 percent. As a result, rapid bone loss is a particular problem in the first year of therapy. The rate of bone loss during initial androgen deprivation therapy may be similar or even higher than the rate of loss seen in women at menopause. Initially, the average bone loss at the hip and spine is 2 to 4 percent per year. The loss of bone may be greatest at the forearm. Most studies report a steady decline of bone density that continues throughout long-term therapy.
What Is Hormonal Therapy?
Hormonal (androgen deprivation) therapy takes away the “fuel” needed for prostate cancer cells to prosper by decreasing testosterone. Until medicines were developed, the only way to reduce male hormones was by surgically removing both testicles. Fortunately, medicines offer another option. Even so, due to other health considerations, surgery may still be necessary and may be used in combination with medicines.
The most common medicines block production of testosterone by tricking the body into thinking there is already enough testosterone. These medicines are called luteinizing hormone-releasing hormone (LHRH) agonists, or you may see them referred to as gonadotropinreleasing hormone (GnRH) agonists. These are given by injection or by small implants placed under the skin that may last up to one year.
| Brand | Generic Name |
| Eligard® Lupron® Viadur® |
leuprolide |
| Trelstar® | triptorelin |
| Vantas® | histrelin |
| Zoladex® | goserelin |
One drug that is similar to LHRH agonists, Firmagon® (generic degarelix), is an LHRH antagonist given once a month by injection. Instead of “trickery,” it directly blocks the pituitary secretion of the hormones that stimulate the production of testosterone. This drug is given either for a short time at the beginning of hormonal therapy before starting the LHRH agonists or on a regular, long-term basis.
It may be necessary to add other drugs to the above treatments from the “anti-androgens” class to further lower testosterone. The preferred anti-androgen is Casodex®(generic bicalutamide). Others include Eulexin® (generic flutamide) or Nilandron® (nilutamide).
Not surprisingly, this translates into lower bone mass and increased fracture rates for men on hormonal therapy. A recent analysis of multiple studies reported that androgen deprivation therapy increased the risk for overall fracture by 23 percent compared with men with prostate cancer not undergoing treatment. Older age and other chronic problems boosted the risk even higher.
Other factors may also contribute to fracture risk. Androgen deprivation therapy also decreases muscle bulk. Low vitamin D was often found in study participants, even in places with abundant sunshine such as south Texas. Loss of muscle mass and low vitamin D contribute to weakness and increased risk of falls, particularly in older men.
What Bone-Related Evaluation Should Be Done If You Are Starting Hormonal Therapy?
Talk with your doctor. Basically, the same general bone health assessment done for women can be applied to men with prostate cancer. You want to try to avoid other risk factors like smoking, too much alcohol (more than two drinks a day), and other bone “unhealthy” medicines.
Lab tests should include a test of your vitamin D level. Make sure your vitamin D is above the minimum level of 30 ng/ml.
A bone density scan is essential. In addition to the routine hip and spine scans, many centers are also including a forearm scan and vertebral fracture assessment. A repeat scan is recommended in one year if you start out low and in two years if you start in the normal range.
What Can You Do to Minimize Bone Loss Caused by Hormonal Therapy?
The key is to start by minimizing risk factors. Ensure that you are taking in 1,200 mg of calcium between your diet and supplements each day. The amount of vitamin D needed to achieve a level above 30 ng/ml will vary from individual to individual. The majority will reach that target with supplements of 800 IU to 2,000 IU daily. Regular physical exercise may help lessen the loss not only of bone but of muscle as well.
No specific drugs are approved by the FDA for preventing or treating osteoporosis in men who are taking hormonal therapy for prostate cancer. Treatment options for preventing bone loss associated with prostate cancer therapies are similar to the treatment options for osteoporosis in men without prostate cancer. Bisphosphonates have been the mainstay in reducing bone loss. In addition to oral Fosamax (generic alendronate), two bisphosphonates given by vein and commonly used in cancer patients are Aredia® (pamidronate) and Zometa (4 mg of zoledronic acid, same medicine as Reclast). These show success in preventing bone loss and even increasing bone density in men receiving hormonal therapy for prostate cancer.
Since estrogens also play a key role in men's bone metabolism, “designer” estrogens, called selective estrogen-receptor modulators or SERMS, may be used. The drugs Evista (raloxifene) and Fareston® (toremifene) increase bone density at the hip and spine as well. Common side effects of these medicines, like hot flashes, possible breast growth, and tendency to develop blood clots, make these drugs a less desirable option.
In a recent randomized controlled trial of over 1,400 men with prostate cancer who were on androgen deprivation therapy, Prolia 60 mg given every six months demonstrated gains in bone density over three years at the spine, hip, and forearm. In contrast, those in the placebo group lost bone. In addition, Prolia accounted for a 62 percent lower risk in new spine fractures at three years compared with placebo. Based on this study, its manufacturer, Amgen, is hoping for FDA approval of Prolia for the treatment and prevention of bone loss in men undergoing hormonal therapy for prostate cancer. Of note, neither bisphosphonates nor SERMS in other similar studies showed gains at the forearm measurement site.
Another strategy includes intermittent administration of hormonal therapy. A “drug-free” period may stop bone loss. However, the risk and benefits of this management approach are still being evaluated for effectiveness in treating prostate cancer.
At present, intravenous bisphosphonates (Aredia and Zometa) are the medicines most commonly used to prevent and treat bone loss in men on hormonal therapy for prostate cancer. With the recent robust results using the new osteoporosis drug Prolia, there will be more use of this agent in the future.
Does Everyone Need to Take a Bone-Specific Drug to Counter the Hormonal Therapy?
An assessment of your bone health with your doctor is going to answer that question. If your bone density is normal and you don't have other risk factors for fracture, bone-specific drugs to counter bone loss with hormonal therapy are not initially needed. You will need to optimize your calcium and vitamin D and improve your nutrition and exercise habits. In addition, you will need careful monitoring of your bone density, with a repeat DXA scan after two years of therapy and on regular intervals after that.
On the other hand, if you start out with low bone density, you do not have bone to lose. You need to maintain every bit you have. In addition to the general bone-health measures, talk with your doctor about bisphosphonates and Prolia as options for preserving or even building up your bone mass to prevent fractures.
Bone is the most likely place for prostate cancer to spread. Just as in breast cancer, bisphosphonates and Prolia may counteract the effect of prostate cancer cells on the bone.
Zometa and a double dose of Prolia (denosumab) formulation, called Xgeva 120 mg, are FDA-approved for use every four weeks to decrease bone complications from prostate cancer that has spread to the bone. In one comparison study of these two agents, Xgeva 120 mg was superior to Zometa 4 mg in prevention of bone-related complications in patients with prostate cancer and bone metastases that progressed despite hormonal therapy. Additional studies are underway to investigate the efficacy of osteoporosis medicines for preventing bone metastases. Others are focused on men with advanced prostate cancer.
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The Bare Bones Hormonal therapy given to some men with prostate cancer causes bone loss and increased fracture risk. Extra measures are needed to protect your bone health:
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