Zoledronat

Zoledronat, also known as zoledronic acid, is a nitrogen-containing bisphosphonate used to alter bone remodeling by inhibiting osteoclast-mediated bone resorption. It is administered by intravenous infusion because oral bioavailability is poor.

The drug acts by inhibiting farnesyl pyrophosphate synthase in the mevalonate pathway, which disrupts osteoclast function and promotes osteoclast apoptosis. Its high affinity for hydroxyapatite in bone provides prolonged antiresorptive effects, allowing relatively infrequent dosing intervals compared with other osteoporosis therapies.

Indications include osteoporosis in postmenopausal women and men at high fracture risk, where it reduces vertebral, hip, and other fractures. In oncology, zoledronat is used to treat hypercalcemia of malignancy and to prevent or treat skeletal-related events in patients with bone metastases from solid tumors or multiple myeloma. It is also approved in some regions for Paget's disease of bone.

Administration and dosing vary by indication. It is given as an intravenous infusion, typically over about 15 minutes. For osteoporosis, the usual dose is 5 mg once yearly. For cancer-related bone disease or hypercalcemia of malignancy, dosing is commonly 4 mg every 3–4 weeks (adjusted by clinical response and renal function) or a one-time/short course regimen for hypercalcemia. Adequate calcium and vitamin D status should be ensured prior to and during therapy.

Common adverse effects include fever and flu-like symptoms after the first infusion, bone or muscle pain, and hypocalcemia. Serious but less frequent risks include renal toxicity, osteonecrosis of the jaw, and, rarely, ocular inflammation or atypical femoral fractures. Contraindications include hypocalcemia, significant renal impairment, pregnancy, lactation, and hypersensitivity. Careful renal monitoring and dental assessment before initiation are recommended.