In patients with bone metastases, osteoclast-inhibiting agents such as denosumab and bisphosphonates significantly decrease the risk of **skeletal-related events** (SREs) (eg, fracture, skeletal instability/loss, spinal cord compression) and can delay symptom onset, fracture formation, need for irradiation, development of hypercalcemia, and possibility of surgical treatment.
Denosumab is a fully human monoclonal antibody that binds to receptor activator of nuclear factor kappa-B ligand (RANKL) and prevents its interaction with RANK, which is an important step in osteoclast activation. Several large randomized trials have shown that denosumab significantly delays SRE onset compared with zoledronic acid (bisphosphonate). Denosumab can be used in a variety of solid tumors. Major side effects are similar to those seen with high potency bisphosphonates (eg, osteonecrosis of the jaw, hypocalcemia). Hypocalcemia and vitamin D deficiency must be corrected before starting therapy. Unlike with zoledronic acid (contraindicated for creatinine clearance <35 mL/min as in this patient), renal dose adjustments are not required, although renal function should be monitored.
Alendronate is an oral bisphosphonate used for prevention and treatment of osteoporosis. It has poor bioavailibility (only 1%-5%). For management of bone metastases, parenteral bisphosphonates (eg, zoledronic acid, pamidronate) or oral ibandronate are indicated. Bisphosponates have more analgesic and cost benefits compared to denosumab. However, they are not recommended in renal failure.