A 70-year-old woman is brought to the emergency department after she tripped and fell at home while getting out of a bathtub. She did not lose consciousness but does have headache and mild right arm pain. Her medical history is significant for advanced breast cancer treated with radical mastectomy and chemotherapy a year ago.
CT of the head is unremarkable. Radiographs of the upper extremities show bone lesions consistent with metastases, but no evidence of fracture. Her serum creatinine level is 1.4 mg/dL (creatinine clearance 30 mL/min), serum calcium level is 9.6 mg/dL, and alkaline phosphatase level is 220 U/L.
The patient is most likely to benefit from which of the following?

Question

A 70-year-old woman is brought to the emergency department after she tripped and fell at home while getting out of a bathtub.  She did not lose consciousness but does have headache and mild right arm pain.  Her medical history is significant for advanced breast cancer treated with radical mastectomy and chemotherapy a year ago.
CT of the head is unremarkable.  Radiographs of the upper extremities show bone lesions consistent with metastases, but no evidence of fracture.  Her serum creatinine level is 1.4 mg/dL (creatinine clearance 30 mL/min), serum calcium level is 9.6 mg/dL, and alkaline phosphatase level is 220 U/L.
The patient is most likely to benefit from which of the following?

Quizplus · Accepted Answer

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. (Choice A) 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. (Choice B) Calcium decreases the risk of bisphosphonate-induced hypocalcemia, and vitamin D is helpful in breast cancer patients who are at risk for vitamin D deficiency. However, they do not significantly impact the evolution of bone metastases. (Choice C) Calcitonin is indicated for Paget disease and is an adjunct in treating hypercalcemia. However, it does not significantly improve bone metastases. (Choice E) Irradiation can provide symptomatic relief of bone pain in patients with bone metastases, but it is only rarely performed for the prevention of SREs from bone metastases. In addition, this patient does not have significant bone pain at metastasis sites. Educational objective: Metastatic cancer patients with bone metastases are susceptible to skeletal-related events (SREs) (eg, fracture, skeletal instability/loss, spinal cord compression). Denosumab and the intravenous bisphosphonates, zoledronic acid and pamidronate, have been shown to prevent SREs and decrease morbidity. Denosumab does not require renal dose adjustments. __________ References: Denosumab compared with zoledronic acid for the treatment of bone metastases in patients with advanced breast cancer: a randomized, double-blind study. (http://www.ncbi.nlm.nih.gov/pubmed/21060033)

A 70-Year-Old Woman Is Brought to the Emergency Department After