• Clinical science



Bisphosphonates (e.g., etidronate, alendronate) are used for the treatment of hypercalcemia and bone metabolism disorders, such as osteoporosis or tumor-induced osteolysis. All bisphosphonates primarily slow down the degradation of bone substance by interfering with osteoclast function. Important side effects of bisphosphonate therapy include hypocalcemia, renal impairment, and aseptic osteonecrosis of the jaw. Therefore, bisphosphonates are contraindicated in patients with hypocalcemia and those with a limited glomerular filtration rate (GFR). Additionally, oral bisphosphonates may cause esophageal damage while IV bisphosphonates can induce flu-like symptoms.

Drug examples

  • Alendronate
  • Risedronate
  • Ibandronate
  • Zoledronate
  • Etidronate
  • Tiludronate


  • Bisphosphonates are pyrophosphate analogs that bind to hydroxyapatite binding sites on the surface of bone tissue: uptake by osteoclasts during phases of bone resorption interference with osteoclast function and promotion of osteoclast apoptosis reduced bone resorption
    • Simple bisphosphonates (tiludronate, etidronate) : reduction of osteoclast proton production, suppression of osteoclast maturation and recruitment, and promotion of osteoclast apoptosis [1]
    • Nitrogen-containing bisphosphonates (alendronate, risedronate, zoledronate): inhibition of the enzyme farnesyl pyrophosphate synthase disturbance of osteoclast metabolism and signaling → reduced osteoclast function and promotion of osteoclast apoptosis [2][3]
  • Inhibit mineralization (structurally similar to pyrophosphate, a natural inhibitor of bone mineralization)

The nitrogen-containing bisphosphonates have a stronger effect than the simple bisphosphonates! [2]

Bisphosphonates also reduce bone formation since bone resorption and formation are intrinsically connected. However, bone resorption is reduced more severely than bone formation.


Adverse effects

Bisphosphonates should be taken in the morning with sufficient water and in an upright position at least 60 minutes before eating!

References: [5][10][11][12][13]

We list the most important adverse effects. The selection is not exhaustive.


References: [5]


  • Reduced GFR (< 30–35 ml/min)
  • Hypocalcemia
  • Esophageal abnormalities (e.g., strictures)
  • Pregnancy/lactation period: no clear contraindications, individual risks/benefits must be weighed

References: [14]

We list the most important contraindications. The selection is not exhaustive.