According to a recent study published in the New England Journal of Medicine, the use of the bisphosphonates may help prevent bone loss caused by androgen-deprivation therapy in men with prostate cancer.

The prostate is a male sex gland that is located between the bladder and the rectum. Prostate cancer is the second leading cause of cancer death in men in the United States. Patients diagnosed with prostate cancer have many treatment options available to them, depending upon the stage, or extent of their disease. Currently, controversy exists regarding the optimal treatment strategy for patients with this disease. As a result, treatment decisions need to be individualized, taking into account the age of the patient and the side effects of treatment. Standard treatment options include radiation therapy, surgery to remove the prostate (prostatectomy), watchful waiting (monitoring PSA levels), hormone therapy (therapy to reduce male hormone levels), cryotherapy (freezing of cancer cells) and/or chemotherapy.

Growth of prostate cancer cells has been shown to be stimulated by male hormones, mainly testosterone. Cancer cells have small proteins to which testosterone binds. This binding action initiates a biochemical cascade within the cell that stimulates the growth of the cancer cell. Hormonal therapy refers to the blocking of the formation of testosterone in the body and/or inhibiting testosterone to enter into a cell. Hormonal therapy is a very common treatment for prostate cancer, whether used alone or in combination with other treatment modalities. Clinical trials are ongoing to determine optimal timing of the use of hormonal therapy in prostate cancer.

Gonadotropin-releasing hormone (GnRH) agonists are common agents utilized for hormonal therapy. GnRH is a hormone initially released by the hypothalamus, creating a sequence of events within the body that ultimately results in the formation of testosterone. GnRH agonists block the effects of GnRH, leading to decreased levels of circulating testosterone. Unfortunately, treatment with GnRH agonists is associated with the development of osteoporosis (loss in bone density), which increases the risk of bone fractures.

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Bisphosphonates are a group of agents that have demonstrated the ability to reduce bone loss in cancer patients with hypercalcemia, bone metastases, Paget’s disease or osteoporosis. This prompted researchers to conduct a clinical trial evaluating the bisphosphonate pamidronate in patients with prostate cancer undergoing hormonal therapy with a GnRH agonist.

In this clinical trial, 41 patients had either advanced or recurrent prostate cancer, with no spread of cancer to the bones. All patients were receiving treatment with leuprolide, a GnRH agonist, and half of the patients also received pamidronate during treatment. Measurements of bone density of the lumbar spine, trochanter (top of the femur) and hip were taken prior to initiation of the trial and approximately one year following treatment. Patients who were treated with leuprolide alone had a significant decrease of bone density in all measured areas. Conversely, patients who received the combination of leuprolide plus the bisphosphonate experienced no significant density change in any measured area.

These results are important as they suggest that the combination of a bisphosphonate in combination with hormonal therapy may prevent osteoporosis and its associated complications such as bone fractures in patients with prostate cancer. Future clinical trials evaluating other agents that have been shown to reduce bone loss are warranted in patients receiving hormonal therapy. Patients with prostate cancer receiving treatment with hormonal therapy may wish to speak with their physician about the risks and benefits of the addition of a bisphosphonate in order to prevent osteoporosis. (New England Journal of Medicine, Vol 345, No 13, pp 948-955, 2001)

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