Zometa is a treatment that helps prevent calcium loss from bones, preventing excessive bone loss in patients with bone metastasis. Its use has been associated with a decrease or delay in patients developing skeletal related events such as collapse of bone or pathologic fractures. Fatigue is not associated with the use of Zometa. Lupron has been associated with fatigue due to its association with creating a castrate state. Without testosterone, patients experience fatigue. Local radiation therapy may cause some additional fatigue. A good diet high in protein and carbohydrates and the use of multi-vitamins is often recommended to help address this. A rising PSA while on Lupron is considered hormonally-resistant prostate cancer. Lupron does not represent a complete androgen blockade, and ideally an anti-androgen such as Casodex would ideally be utilized, however given your husband's inability to tolerate this agent, this is not going to be possible. Other antipandrogens such as flutamide can be tried, but in all likelihood, if your husband is not able to tolerate the Casodex, it is unlikely that he would be able to tolerate the flutamide. Hormonally resistant disease is difficult to treat and chemotherapeutic alternative may be considered. A consultation with an oncologist is something that you should consider.