• 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.


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


Side effects

  • General
    • Hypocalcemia and hypophosphatemia (hypocalcemia can also lead to osteomalacia, see osteomalacia and rickets)
    • Aseptic osteonecrosis of the jaw: mostly in high-dose IV administration in tumor patients, but can also occur with oral administration and in other patients
    • Atypical fractures (particularly of the femur)
    • Musculoskeletal pain
    • Atrial fibrillation
    • Renal impairment
    • Ocular inflammation and visual disturbances
  • Oral bisphosphonates; (alendronate, risedronate, etidronate, tiludronate): esophageal inflammation and cancer
  • IV bisphosphonates (zolendronate); : acute-phase reaction with flulike symptoms; (e.g., fever, joint, and muscle pain) 24–72 hours after administration

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


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




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


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