Bisphosphonates

Last updated: July 1, 2022

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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.

References:[1][2][3][4][5][6][7][8][9]

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]

  • Common to all bisphosphonates
    • Hypersensitivity
    • Esophageal abnormalities (e.g., strictures)
    • Inability to stand or sit upright for at least 30 minutes after oral bisphosphonate therapy
  • For zoledronic acid
  • Pregnancy/lactation period: no clear contraindications, individual risks/benefits must be weighed

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
  3. Tsoumpra MK, Muniz JR, Barnett BL, et al. The inhibition of human farnesyl pyrophosphate synthase by nitrogen-containing bisphosphonates. Elucidating the role of active site threonine 201 and tyrosine 204 residues using enzyme mutants. Bone. 2015; 81 : p.478-486. doi: 10.1016/j.bone.2015.08.020 . | Open in Read by QxMD
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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. https://www.uptodate.com/contents/risks-of-bisphosphonate-therapy-in-patients-with-osteoporosis?source=search_result&search=bisphosphonates&selectedTitle=3~150#H4000454.Last 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. http://www.rheumatology.org/I-Am-A/Patient-Caregiver/Diseases-Conditions/Osteonecrosis-of-the-Jaw-ONJ. 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. Jeremiah MP, Unwin BK, Greenawald MH, Casiano VE. Diagnosis and Management of Osteoporosis. Am Fam Physician. 2015; 92 (4): p.261-8.

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