**Core Concept**
Hypercalcemia of malignancy is a condition characterized by elevated serum calcium levels, often resulting from the proliferation of cancer cells that produce parathyroid hormone-related protein (PTHrP) or other factors that stimulate osteoclast activity. This condition requires prompt treatment to prevent severe complications.

**Why the Correct Answer is Right**
The preferred treatment for hypercalcemia of malignancy is bisphosphonates, specifically zoledronic acid. These drugs inhibit osteoclast-mediated bone resorption, thereby reducing serum calcium levels. Zoledronic acid is administered intravenously and has a rapid onset of action, making it an effective treatment option. Additionally, bisphosphonates have the advantage of being able to be administered on an outpatient basis, which is beneficial in the management of cancer patients.

**Why Each Wrong Option is Incorrect**
**Option A:** **Plicamycin** is a calcitonin analogue that can be used to treat hypercalcemia, but it is not the first-line treatment and is associated with more side effects compared to bisphosphonates.
**Option B:** **Denosumab** is a monoclonal antibody that targets RANKL and inhibits osteoclast formation, but it is typically reserved for patients with refractory hypercalcemia or those who cannot tolerate bisphosphonates.
**Option C:** **Hydration and loop diuretics** are essential components of treatment for hypercalcemia, but they do not address the underlying cause of the elevated calcium levels and are used in conjunction with bisphosphonates or other treatments.

**Clinical Pearl / High-Yield Fact**
In the management of hypercalcemia of malignancy, it is essential to consider the underlying cause of the elevated calcium levels and tailor treatment accordingly. Bisphosphonates, such as zoledronic acid, are a cornerstone of treatment and should be initiated promptly to prevent severe complications.

**Correct Answer: C. Zoledronic acid**