Clodronate to Prevent Bone Metastases in Prostate Cancer

Neha Vapiwala MD
Last Modified: March 27, 2007

Dear OncoLink "Ask the Experts,"
Are there any studies where clodronate has been used to prevent bone metastases in patients with advanced prostate cancer? In the situation to which I am referring, a radical prostatectomy has been performed, followed by radiation therapy. The use of Lupron and Casodex also has been instituted. Thus, the patient has stage IV prostate cancer with a Gleason score of nine. It would appear that clodronate would be useful in hindering bone metastases in prostate cancer as well as it has in breast cancer. Any information you can provide would be much appreciated.

Thank you for your assistance.
E.M.

Neha Vapiwala MD, Senior Editor for Oncolink, responds:

Dear E.M.,
Thank you for your interest and question.

Clodronate (brand name, Ostac) is a bisphosphonate, which is a class of drugs that inhibits the function of osteoclasts. (Osteoclasts are cells that are responsible for breaking down existing bone so that new bone can be laid down by cells called osteoblasts. This is called bone remodeling and occurs in a normal health person throughout one's lifetime). Other examples of bisphosphonates include pamidronate and etidronate. The way that bone cancers (whether they started in the bone or are metastases from other primary cancers) cause destruction is by producing and releasing local growth factors that in turn increase the activity of osteoclasts to abnormal levels. The osteoclasts weaken the bony structure and result in osteolytic lesions, because normal osteoblasts can not keep up to repair the damage and lay down new bone. This applies to most cancers, including multiple myeloma and breast cancer. Some bisphosphonates have been proven to be very successful in reducing the number of “skeletal events” (extent of bony metastases, clinical fractures, time to bone progression, severity of bony pain, etc.) in these cancers.

Does this apply to prostate cancer patients with advanced disease? The answer is that the use of bisphosphonates is not fully proven in prostate cancer. Two prospective randomized trials (one published in 1989 using etidronate and the other in 1992 using clodronate) have examined the effectiveness of bisphosphonates in prostate cancer patients with documented bony metastases. Both demonstrated a slight improvement in subjective pain, but these were not statistically significant. No differences were demonstrated in the number of bony metastases seen on bone scan in the clodronate study, while skeletal events were not even addressed in the etidronate article.

One explanation for the limited efficacy of bisphosphonates in prostate cancer is that metastases to bone from prostate cancer are typically osteoblastic (sclerotic) lesions and not osteolytic (which are dependent on osteoclasts, as described above). Thus, inhibiting osteoclasts with bisphosphonates would be expected to have little success in preventing most bone metastases from prostate cancer.

Having said that, bisphosphonates should certainly be considered as a treatment option for metastatic prostate cancer patients who have refractory bone pain and would greatly benefit from prevention of skeletal events. Such an intervention can profoundly improve the quality of life of these patients, but additional research is needed to guide the optimal use of bisphosphonates.