Pharmacologic strategies for osteoporosis prevention and treatment include oral bisphosphonates (e.g., alendronate, pamidronate), intravenous bisphosphonates (e.g., zoledronic acid), and subcutaneous RANK ligand inhibitors (e.g., denosumab). It is important to note that the recommended dose and treatment schedules for zoledronic acid and denosumab are different for the indications of osteoporotic fracture prevention and SRE prevention. For example, zoledronic acid is usually administered yearly for osteoporosis-related fracture prevention compared to monthly or every three months for metastatic cancer SRE prevention. Similarly, denosumab has been administered as 60mg every 6 months for osteoporosis compared to 120mg monthly for SRE prevention. A meta-analysis156 included 15 trials of 2,634 men with prostate cancer receiving ADT (with or without bone metastases) randomized to receive a bisphosphonate versus placebo. A meta-analysis156 included 15 trials of 2,634 men with prostate cancer receiving ADT (with or without bone metastases) randomized to receive a bisphosphonate versus placebo. Men receiving bisphosphonates had significantly reduced risk of osteoporosis (RR=0.39; 95% CI: 0.28 to 0.55; number needed to treat [NNT] to prevent one additional patient with osteoporosis: 2.82). Osteoporosis-related fractures were also reduced among patients treated with bisphosphonates (RR=0.80; 95% CI: 0.69 to 0.94; NNT to prevent one additional fracture: 167). Amongst bisphosphonates, the greatest reduction in fractures was observed for zoledronic acid (NNT: 14.9). Denosumab increases bone mineral density in prostate cancer patients and reduces fracture risk as well. In a trial of 1,468 men receiving ADT for prostate cancer,157 patients were randomly assigned to denosumab (60mg every 6 months) versus placebo. After 36 months, men receiving denosumab significantly increased bone mineral density at all measured sites and decreased risk of vertebral fractures at 36 months following randomization (1.5% versus 3.9%; RR=0.38; 95% CI: 0.19 to 0.78; p=0.006). Given the uncertainties of management of osteopenia and osteoporosis in prostate cancer patients at risk for bone fractures, referral to physicians who have familiarity with management of osteoporosis should be considered for select patients. These may include endocrinologists, orthopedic surgeons, primary care physicians, or other specialists who focus on bone heath. Additionally, an uncommon but serious toxicity of bisphosphonates or denosumab is osteonecrosis of the jaw (ONJ). Because men who need dental extractions while on these agents are at higher risk for ONJ, clinicians should consider evaluation by a dentist prior to initiation.