Last updated: August 12, 2021

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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.

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

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.


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

References: [5][11][12][13][14]

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: [15]

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

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  2. Russell RGG. Bisphosphonates: Mode of Action and Pharmacology. Pediatrics. 2007; 119 (Supplement 2): p.S150-S162. doi: 10.1542/peds.2006-2023h . | Open in Read by QxMD
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  6. Bisphosphonates. . Accessed: February 21, 2017.
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  10. Walton RJ, Russell RG, Smith R. Changes in the renal and extrarenal handling of phosphate induced by disodium etidronate (EHDP) in man.. Clin Sci Mol Med. 1975; 49 (1): p.45-56. doi: 10.1042/cs0490045 . | Open in Read by QxMD
  11. Rosen HN. Risks of bisphosphonate therapy in patients with osteoporosis. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. updated: January 6, 2016. Accessed: February 21, 2017.
  12. Rosella D, Papi P, Giardino R, Cicalini E, Piccoli L, Pompa G. Medication-related osteonecrosis of the jaw: Clinical and practical guidelines. J Int Soc Prev Community Dent. 2016; 6 (2): p.97–104. doi: 10.4103/2231-0762.178742 . | Open in Read by QxMD
  13. Osteonecrosis of the Jaw. Updated: September 1, 2013. Accessed: February 21, 2017.
  14. Liamis G, Milionis HJ, Elisaf M. Medication-induced hypophosphatemia: a review. QJM. 2010; 103 (7): p.449-459. doi: 10.1093/qjmed/hcq039 . | Open in Read by QxMD
  15. Lexicomp.. Alendronate: Drug information. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. updated: January 1, 2018. Accessed: January 29, 2018.
  16. Herold G. Internal Medicine. Herold G ; 2014

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