The main purpose of this study is to look at the effects (good or bad) that Atrasentan given alone and Atrasentan given with Zometa has on levels of bone formation and bone destruction in men with prostate cancer that has spread to the bones.

• Patients will be randomized to either receive Atrasentan alone or Atrasentan plus Zometa.
• Patients receiving Atrasentan alone will receive this drug in pill form once daily for 12 weeks. Patients will have a physical exam, blood work, and a urine sample performed once every other week during the first four weeks of medication administration. After those two initial visits, they will return to the clinic once every 4 weeks to have the same tests repeated. A bone scan and abdominal-pelvic CT Scan will be done every 12 weeks.
• After the patient has been taking Atrasentan for 12 weeks, if the disease has not progressed, they will begin combination treatment of Atrasentan and Zometa.
• Patients receiving Atrasentan plus Zometa, receive Zometa intravenously and then immediately start Atrasentan orally once daily as long as they remain on the study. Patients will return to the clinic twice over the first 4 weeks (once every other week) to have a physical exam, blood work and urine test performed. After these two initial visits, they will return to the clinic once every 4 weeks to have the tests repeated and to receive another treatment of zometa. A bone scan and an abdominal-pelvic CT Scan will be done once every 12 weeks.
• Patients participation in this study will last as long as the disease does not progress and they are not experiencing any serious side effects.

Inclusion Criteria:

• Histologically confirmed adenocarcinoma of the prostate
• History of bilateral orchiectomy or current treatment with a GnRH agonist or antagonist
• Radiographically documented bone metastases
• Disease progression according to criteria from the PSA Working Group

Exclusion Criteria:

• Prior treatment with Atrasentan or Zometa within one year
• Serum creatinine > 2.0mg/dL
• Documented cardiovascular disability status of New York Heart Association Class 2
• Treatment with chemotherapy, radiation, steroids, estrogens, or PC-SPES within 6 weeks
• Treatment with bisphosphonates or radiopharmaceuticals within 12 weeks
• History of Paget's disease, hyperthyroidism, hyperparathyroidism, Cushing's syndrome, hyperprolactinemia or other disorder associated with metabolic bone disease.