[Durgical](https://durgical.com/en/) › [DurgiPedia](https://durgical.com/en/durgipedia/) › [Pharmacology](https://durgical.com/en/pharmacology/) › [Bisphosphonates](https://durgical.com/en/pharmacology/classes/bisphosphonates/) › Zoledronic acid # Zoledronic acid ## Bisphosphonates? Bisphosphonates The most potent bisphosphonate, given as an intravenous infusion for hypercalcaemia of malignancy, bone metastases, myeloma and osteoporosis. Updated Nov 1, 2026 Also called: Zoledronate ## Quick facts **Group** [Bisphosphonates](https://durgical.com/en/pharmacology/classes/bisphosphonates/) **Target** Farnesyl pyrophosphate synthase (FPPS), an enzyme of the mevalonate pathway in osteoclasts **Used for** Hypercalcaemia of malignancy · Multiple myeloma **Key effects** Acute-phase reaction in the first days · Nausea **Monitor** Serum creatinine before each dose · Calcium **ATC** M05BA08 No doses: the clinician sets them by the current guideline. On this page - The basics Mechanism of action - Indications - Adverse effects - Pharmacokinetics - Memory aid - Safety Contraindications - Key interactions - What is monitored - Administration and safety - Pregnancy and breastfeeding - Nursing care - Study Test yourself - Connections Connections ## Mechanism of action ✂**Farnesyl pyrophosphate synthase (FPPS), an enzyme of the mevalonate pathway in osteoclasts**Zoledronic acid ⓘ The figure shows zoledronic acid itself in the active site of human farnesyl pyrophosphate synthase, with magnesium ions and the substrate isopentenyl diphosphate. **Target in 3D:** Farnesyl pyrophosphate synthase (FPPS), an enzyme of the mevalonate pathway in osteoclasts. PDB structure 1ZW5 (RCSB PDB, public domain). [View the structure at RCSB PDB](https://www.rcsb.org/structure/1ZW5) · Drag to rotate · pinch to zoom Zoledronic acid is a nitrogen-containing bisphosphonate with an imidazole ring. It binds avidly to bone mineral, enters osteoclasts and inhibits farnesyl pyrophosphate synthase, so osteoclasts stop resorbing bone. In cancer this lowers the calcium that tumours release from bone and reduces skeletal events; in osteoporosis an infusion keeps resorption suppressed for a long time. - The infusion delivers zoledronic acid straight to bone mineral - Osteoclasts take it up during resorption - It blocks farnesyl pyrophosphate synthase in the osteoclast - Resorption falls: serum calcium drops and bone is protected ## Indications - Hypercalcaemia of malignancy [Hypercalcaemia of malignancy →](https://durgical.com/en/conditions/hypercalcaemia-of-malignancy/) - Multiple myeloma and bone metastases from solid tumours (with cancer treatment) [Multiple myeloma →](https://durgical.com/en/conditions/multiple-myeloma/) - Osteoporosis (infusion at long intervals) [Osteoporosis →](https://durgical.com/en/conditions/osteoporosis/) - Paget disease of bone [Paget disease of bone →](https://durgical.com/en/conditions/paget-disease-of-bone/) ## Adverse effects ### Common - Acute-phase reaction in the first days: fever, chills, headache, bone and muscle pain - Nausea, vomiting, loss of appetite - Fatigue - Pain or swelling at the infusion site - Eye redness or inflammation ### Serious (rare, important) - Kidney toxicity, more likely with kidney disease, dehydration or other nephrotoxic drugs - Hypocalcaemia, which can be severe - Osteonecrosis of the jaw (more common at oncology doses) - Atypical femoral fractures - Severe musculoskeletal pain - Bronchospasm in aspirin-sensitive asthma ## Contraindications - Hypersensitivity to zoledronic acid or other components - Uncorrected hypocalcaemia - Not recommended with severe kidney impairment - Not combined with another product that contains zoledronic acid or another bisphosphonate ## Key interactions **Aminoglycosides and calcitonin** Additive, prolonged fall in serum calcium **Loop diuretics** More risk of hypocalcaemia; they are not used before the person is rehydrated **Other nephrotoxic drugs (e.g. NSAIDs)** More kidney damage ## What is monitored - Serum creatinine before each dose - Calcium, phosphate and magnesium - Hydration status - Dental examination before starting - Thigh or groin pain ## Administration and safety - Given only as an intravenous infusion by staff, never as a rapid push, over the time the label states - Uses its own line and is not mixed with solutions that contain calcium or other divalent cations - The person is well hydrated before the infusion - Oncology and osteoporosis products have different strengths and schedules; check which one is ordered (same active ingredient) ## Pregnancy and breastfeeding Can harm the fetus; pregnancy is ruled out before treatment, and because the drug stays in bone the risk may persist after the last dose. ## Nursing care - Check creatinine and calcium before the infusion; report abnormal results - Encourage fluids before the dose as ordered and watch urine output - Explain the flu-like reaction of the first days; report fever that lasts or severe pain - Ask about dental work and teach good oral hygiene - Watch for numbness, tingling or cramps (hypocalcaemia) ## Pharmacokinetics **Absorption** Given only intravenously **Distribution** A large part binds bone and is released slowly **Metabolism** Not metabolised and does not affect CYP enzymes **Elimination** Unchanged by the kidney; clearance falls with kidney function ## Memory aid ZOLedronic = ZOne of Last resort for calcium: Zap osteoclasts, One infusion, Look at creatinine. ## Test yourself Think of the answer, then tap the question to see it. ## What must be checked before every dose of zoledronic acid? Serum creatinine (it is cleared unchanged by the kidney and can damage it), plus calcium and hydration. ## What is the acute-phase reaction after zoledronic acid? Fever, chills, headache and bone or muscle pain in the first days after an infusion, usually self-limited. ## Why are loop diuretics delayed until a person with hypercalcaemia is rehydrated? Given to a dehydrated person they worsen volume depletion and kidney function; after rehydration they also add to the risk of hypocalcaemia with zoledronic acid. [Add to my cards (3)](https://durgical.app/estudiar/?add=/en/pharmacology/zoledronic-acid/) [More Pharmacology questions →](https://durgical.com/en/practice/?f=pharmacology) ## Connections ## Related drugs 3 - [Alendronic acid (alendronate)](https://durgical.com/en/pharmacology/alendronic-acid/) - [Denosumab](https://durgical.com/en/pharmacology/denosumab/) - [Calcitonin (salmon)](https://durgical.com/en/pharmacology/calcitonin/) ## Related conditions 4 - [Hypercalcaemia of malignancy](https://durgical.com/en/conditions/hypercalcaemia-of-malignancy/) - [Multiple myeloma](https://durgical.com/en/conditions/multiple-myeloma/) - [Osteoporosis](https://durgical.com/en/conditions/osteoporosis/) - [Paget disease of bone](https://durgical.com/en/conditions/paget-disease-of-bone/) [← Back to the class: Bisphosphonates](https://durgical.com/en/pharmacology/classes/bisphosphonates/) Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given. Sources: [Zoledronic Acid Injection: MedlinePlus Drug Information](https://medlineplus.gov/druginfo/meds/a605023.html) (MedlinePlus (U.S. National Library of Medicine), 2026); [DailyMed - ZOLEDRONIC ACID injection](https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=3df715a1-2562-4374-a383-6edc33c6e52f) (DailyMed (U.S. National Library of Medicine), 2026); [ATCDDD - ATC/DDD Index](https://atcddd.fhi.no/atc_ddd_index/?code=M05BA08) (WHO Collaborating Centre for Drug Statistics Methodology, 2026); [eEML - Electronic Essential Medicines List](https://list.essentialmeds.org/) (World Health Organization, 2025). ## **Spotted a mistake?** We are always improving for the community. Tell us what is wrong and our team will review it. Report a mistake Representative model, for educational purposes only. --- Source: https://durgical.com/en/pharmacology/zoledronic-acid/ License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/pharmacology/zoledronic-acid/