Bisphosphonates
Bone-seeking drugs that slow the cells that break bone down. The first-line treatment of osteoporosis and of Paget disease of bone.
What they are
Analogues of pyrophosphate that bind tightly to bone mineral and are taken up by osteoclasts. They are used to prevent fractures in osteoporosis (postmenopausal, male and glucocorticoid-induced), in Paget disease of bone, and, given intravenously, in hypercalcaemia of malignancy and bone disease from myeloma or metastases. Oral forms are poorly absorbed and irritate the oesophagus; intravenous zoledronic acid avoids the gut but needs good kidney function.
Mechanism of action
They attach to hydroxyapatite where bone is being resorbed. Osteoclasts take them up as they dissolve the bone. The nitrogen-containing bisphosphonates (alendronate, risedronate, zoledronate) inhibit farnesyl pyrophosphate synthase in the mevalonate pathway, which osteoclasts need to survive and work. Resorption falls, and over months bone formation outpaces resorption, so bone density rises. Because they stay in bone, their effect lasts long after the last dose.
Target: Farnesyl pyrophosphate synthase (FDPS) in osteoclasts, after binding to bone mineral
Drugs in this class
- Alendronic acid (alendronate)An oral bisphosphonate that slows bone loss and lowers fracture risk in osteoporosis. It must be taken in a strict way…Farnesyl pyrophosphate synthase (FPPS), an enzyme of the mevalonate pathway in osteoclasts
- Zoledronic acidThe most potent bisphosphonate, given as an intravenous infusion for hypercalcaemia of malignancy, bone metastases…Farnesyl pyrophosphate synthase (FPPS), an enzyme of the mevalonate pathway in osteoclasts
- Risedronic acid (risedronate)An oral bisphosphonate for osteoporosis and Paget disease, taken under the same strict rules as alendronate to protect…Farnesyl pyrophosphate synthase (FPPS), an enzyme of the mevalonate pathway in osteoclasts
- Ibandronic acidA nitrogen-containing bisphosphonate taken by mouth or given into a vein. It slows bone loss in postmenopausal…Farnesyl pyrophosphate synthase (FPPS) in osteoclasts
- Pamidronic acidAn intravenous bisphosphonate. It lowers high calcium from cancer and protects bone in myeloma, bone metastases and…Farnesyl pyrophosphate synthase (FPPS) in osteoclasts
Others in the class
- Ibandronic acid
- Pamidronic acid
- Etidronic acid
- Clodronic acid
Test yourself
Think of the answer, then tap the question to see it.
Which enzyme do nitrogen-containing bisphosphonates inhibit in osteoclasts?
Farnesyl pyrophosphate synthase, in the mevalonate pathway; without it osteoclasts cannot prenylate key proteins, so they stop resorbing bone and die.
Why must a person stay upright after swallowing alendronate?
Lying down lets the tablet or its solution reflux and sit in the oesophagus, where it can cause oesophagitis, ulcers and strictures.
A woman on a bisphosphonate for years develops dull thigh pain. What must be ruled out?
An atypical (low-energy) femoral shaft fracture, which may be incomplete and bilateral; she needs imaging and reassessment of the drug.
Why does the effect of a bisphosphonate persist after it is stopped?
The drug is stored in the bone matrix and released slowly over years, so resorption stays suppressed (the basis of drug holidays).
Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.
Sources: Alendronate: MedlinePlus Drug Information (MedlinePlus (U.S. National Library of Medicine), 2026); DailyMed - ALENDRONATE SODIUM tablet (DailyMed (U.S. National Library of Medicine), 2026); DailyMed - ZOLEDRONIC ACID injection (DailyMed (U.S. National Library of Medicine), 2026).
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Representative model, for educational purposes only.