drug adverse effects of bisphosphonates
Jump to navigation
Jump to search
[1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36]
Adverse effects
- nausea/vomiting
- erosive esophagitis
- not associated with increase risk of esophageal cancer or gastric cancer despite association with erosive esophagitis[14]
- associated with esophageal cancer in patients taking 10 or more prescriptions[15]
- evidence inconclusive on risk of esophageal cancer[19]
- insufficient data to recommend endoscopic screening of asymptomatic patients[19]
- oral bisphosphates contraindicated in patients with esophageal varices
- severe bone pain, myalgias & arthralgias may occur with bisphosphonates[1][8]
- these adverse effects may occur with standard doses from the start of therapy
- the pain may resolve with discontinuation
- alendronate & risedronate are specificically implicated, but this is probably generalizable to bisphosphates as a class.
- osteonecrosis of the jaw[2][4][6][18][27]
- patients receiving intravenous bisphosphonates at highest risk
- many cases associated with infections following dental procedures, especially tooth extractions
- link between oral bisphosphonate use & jaw osteonecrosis; absolute risk is very low[18]
- Recommendations:
- cancer patients should receive a dental examination prior to initiating therapy with intravenous bisphosphonates
- extract any teeth that are nonrestorable prior to starting bisphosphonate
- avoid invasive dental procedures while receiving intravenous bisphosphonate
- for patients who develop osteonecrosis of the jaw while on bisphosphonate therapy, dental surgery may exacerbate the condition
- atypical subtrochanteric stress fractures[12]
- after prolonged bisphosphonate use, especially > 5 years
- suppression of bone turnover & accumulation of microdamage is a postulated mechanism[11]
- no clear association, but FDA is investigating[12]
- intermediate-term use of bisphosphonates does not elevate risk[13]
- overall risk < 0.08% over 3 years[13]
- after >= 5 years odds ratio = 2.74 (women)[16]
- relative risk increased by bisphosphonate use
- benefits of bisphosphonate use exceed risks (if indicated)
- relative risk large (> 30), absolute risk small[22]
- risk falls rapidly after discontinuaton[17]
- IV bisphosphonates may cause transient hypocalcemia[3]
- treat hypocalcemia, vitamin D deficiency prior to starting IV bisphosphonates[25]
- IV bisphosphonates may cause acute tubular necrosis[25]
- ocular inflammation: uveitis & scleritis[3][21][22]
- association with atrial fibrillation ?[5]
- not linked to gastrointestinal cancers[24]
- increases bone mineral density, but also increases risk of hip fracture in primary hyperparathyroidism relative to observation (RR=1.5)[29]
- increased risk of acute angle closure glaucoma (RR=1.8, 2.1 for residronate)[36]
Management
- prophylaxis/prevention osteonecrosis of the jaw for bisphosphonates administered IV
- dental consultation
- no active oral infection
- biannual dental care for
- teeth cleaning
- minizing periodontal inflammation
- addressing caries
- endodontic care for non restorable teeth
- dental consultation
More general terms
References
- ↑ Jump up to: 1.0 1.1 Prescriber's Letter 12(4): 2005 Bone, Muscle, and Joint Problems with Bisphosphonates Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=210403&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ Jump up to: 2.0 2.1 Internal Medicine News, April 15, 2005
Prescriber's Letter 12(5): 2005 Bisphosphonate-associated Jaw Osteonecrosis Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=210511&pb=PRL (subscription needed) http://www.prescribersletter.com
FDA Safteywatch http://www.fda.gov/medwatch/SAFETY/2005/safety05.htm#zometa2 - ↑ Jump up to: 3.0 3.1 3.2 Prescriber's Letter 12(5): 2005 New Formulation: Ibandronate (Boniva) Injection Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=220304&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ Jump up to: 4.0 4.1 Prescriber's Letter 13(8): 2006 Bisphosphonates and Jaw Bone Damage Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=220801&pb=PRL (subscription needed) http://www.prescribersletter.com
Favia G et al. Osteonecrosis of the jaw correlated to bisphosphonate therapy in non-oncologic patients: Clinicopathological features of 24 patients. J Rheumatol 2009 Dec; 36:2780 http://dx.doi.org/10.3899/jrheum.090455 PMID: https://www.ncbi.nlm.nih.gov/pubmed/19884275 - ↑ Jump up to: 5.0 5.1 Prescriber's Letter 14(6): 2007 New Developments With Bisphosphonate Therapy Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=230613&pb=PRL (subscription needed) http://www.prescribersletter.com
Prescriber's Letter 15(6): 2008 Bisphosphonates and the Risk of Atrial Fibrillation Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=240605&pb=PRL (subscription needed) http://www.prescribersletter.com - ↑ Jump up to: 6.0 6.1 Wilkinson GS et al, Intravenous bisphosphonate therapy and inflammatory conditions or surgery of the jaw: A population-bases analysis. J Natl Cancer Inst 2007, 99:1016 PMID: https://www.ncbi.nlm.nih.gov/pubmed/17596574
- ↑ Jump up to: 7.0 7.1 FDA Medwatch http://www.fda.gov/medwatch/safety/2007/safety07.htm#Bisphosphonates
- ↑ Jump up to: 8.0 8.1 FDA Medwatch http://www.fda.gov/medwatch/safety/2008/safety08.htm#Bisphosphonates
- ↑ FDA Medwatch http://www.fda.gov/medwatch/safety/2008/safety08.htm#bisphosphonates2
- ↑ Prescriber's Letter 16(3): 2009 Summary of the Latest Guidelines on Bisphosphonate-Induced Osteonecrosis Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=250303&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ Jump up to: 11.0 11.1 Capeci CM and Tejwani NC. Bilateral low-energy simultaneous or sequential femoral fractures in patients on long-term alendronate therapy. J Bone Joint Surg Am 2009 Nov; 91:2556. PMID: https://www.ncbi.nlm.nih.gov/pubmed/19884427
Lenart BA et al. Association of low-energy femoral fractures with prolonged bisphosphonate use: A case control study. Osteoporos Int 2009 Aug; 20:1353. PMID: https://www.ncbi.nlm.nih.gov/pubmed/19066707 - ↑ Jump up to: 12.0 12.1 12.2 FDA Medwatch Oral Bisphosphonates: Ongoing Safety Review of Atypical Subtrochanteric Femur Fractures http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm204127.htm
Black DM et al Bisphosphonates and Fractures of the Subtrochanteric or Diaphyseal Femur N Engl J Med. 2010 Mar 24. <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/20335571 <Internet> http://content.nejm.org/cgi/content/full/NEJMoa1001086 - ↑ Jump up to: 13.0 13.1 13.2 Black DM et al. Bisphosphonates and fractures of the subtrochanteric or diaphyseal femur. N Engl J Med 2010 Mar 24; <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/20335571 <Internet> http://dx.doi.org/10.1056/NEJMoa1001086
- ↑ Jump up to: 14.0 14.1 Cardwell CR et al Exposure to Oral Bisphosphonates and Risk of Esophageal Cancer JAMA. 2010;304(6):657-663. <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/20699457 <Internet> http://jama.ama-assn.org/cgi/content/short/304/6/657 doi:10.1001/jama.2010.1098
Wysowski DK Reports of Esophageal Cancer with Oral Bisphosphonate Use N Engl J Med 2009; 360:89-90 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/19118315 <Internet> http://www.nejm.org/doi/full/10.1056/NEJMc0808738
Abrahamsen B et al More on Reports of Esophageal Cancer with Oral Bisphosphonate Use N Engl J Med 2009; 360:1789-1792 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/19387022 <Internet> http://www.nejm.org/doi/full/10.1056/NEJMc096026 - ↑ Jump up to: 15.0 15.1 Green J et al. Oral bisphosphonates and risk of cancer of oesophagus, stomach, and colorectum: Case-control analysis within a UK primary care cohort. BMJ 2010 Sep 2; 341:c4444. PMID: https://www.ncbi.nlm.nih.gov/pubmed/20813820
- ↑ Jump up to: 16.0 16.1 Park-Wyllie LY et al, Bisphosphonate Use and the Risk of Subtrochanteric or Femoral Shaft Fractures in Older Women JAMA. 2011;305(8):783-789 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/21343577 <Internet> http://jama.ama-assn.org/content/305/8/783.full
- ↑ Jump up to: 17.0 17.1 Schilcher J et al. Bisphosphonate use and atypical fractures of the femoral shaft. N Engl J Med 2011 May 5; 364:1728. PMID: https://www.ncbi.nlm.nih.gov/pubmed/21542743
- ↑ Jump up to: 18.0 18.1 18.2 Barasch A et al. Risk factors for osteonecrosis of the jaws: A case-control study from the CONDOR Dental PBRN. J Dent Res 2011 Apr; 90:439 PMID: https://www.ncbi.nlm.nih.gov/pubmed/21317246
Fellows JL et al. ONJ in two dental practice-based research network regions. J Dent Res 2011 Apr; 90:433. PMID: https://www.ncbi.nlm.nih.gov/pubmed/21317245 - ↑ Jump up to: 19.0 19.1 19.2 FDA MedWatch: 07/21/2011 Oral Osteoporosis Drugs (bisphosphonates): Drug Safety Communication - Potential Increased Risk of Esophageal Cancer http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm264087.htm
- ↑ Geriatric Review Syllabus, 7th edition Parada JT et al (eds) American Geriatrics Society, 2010
- ↑ Jump up to: 21.0 21.1 21.2 Etminan M et al Inflammatory ocular adverse events with the use of oral bisphosphonates: a retrospective cohort study CMAJ 2012 May 15; 184:E431. <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/22470169 <Internet> http://www.cmaj.ca/content/early/2012/04/02/cmaj.111752.full.pdf+html
- ↑ Jump up to: 22.0 22.1 22.2 Meier RPH et al. Increasing occurrence of atypical femoral fractures associated with bisphosphonate use. Arch Intern Med. 2012 Jun 25;172(12):930-6. <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/22732749 <Internet> http://archinte.jamanetwork.com/article.aspx?doi=10.1001/archinternmed.2012.1796
Bauer DC. Atypical femoral fracture risk in patients treated with bisphosphonates. Arch Intern Med. 2012 Jun 25;172(12):936-7. <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/22732750 <Internet> http://archinte.jamanetwork.com/article.aspx?doi=10.1001/archinternmed.2012.1827 - ↑ Jump up to: 23.0 23.1 Schneider JP et al. Atypical femur fractures: 81 individual personal histories. J Clin Endocrinol Metab 2012 Dec; 97:4324 PMID: https://www.ncbi.nlm.nih.gov/pubmed/23076349
- ↑ Jump up to: 24.0 24.1 Vinogradova Y et al. Exposure to bisphosphonates and risk of gastrointestinal cancers: Series of nested case-control studies with QResearch and CPRD data. BMJ 2013 Jan 16; 346:f114. PMID: https://www.ncbi.nlm.nih.gov/pubmed/23325866
- ↑ Jump up to: 25.0 25.1 25.2 Medical Knowledge Self Assessment Program (MKSAP) 16, 18 American College of Physicians, Philadelphia 2012, 2018
- ↑ Fehm T, Felsenberg D, Krimmel M et al Bisphosphonate-associated osteonecrosis of the jaw in breast cancer patients: recommendations for prevention and treatment. Breast. 2009 Aug;18(4):213-7. PMID: https://www.ncbi.nlm.nih.gov/pubmed/19651512
- ↑ Jump up to: 27.0 27.1 Shannon J, Shannon J, Modelevsky S, Grippo AA. Bisphosphonates and osteonecrosis of the jaw. J Am Geriatr Soc. 2011 Dec;59(12):2350-5. Review. PMID: https://www.ncbi.nlm.nih.gov/pubmed/22091898
- ↑ Crandall CJ et al Comparative Effectiveness of Pharmacologic Treatments to Prevent Fractures: An Updated Systematic Review. Ann Intern Med. Published online 9 September 2014 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/25199883 <Internet> http://annals.org/article.aspx?articleid=1902273
- ↑ Jump up to: 29.0 29.1 Yeh MW, Zhou H, Adams AL et al The Relationship of Parathyroidectomy and Bisphosphonates With Fracture Risk in Primary Hyperparathyroidism: An Observational Study. Ann Intern Med. Published online 5 April 2016 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/27043778 <Internet> http://annals.org/article.aspx?articleid=2511009
- ↑ Gedmintas L, Solomon DH, Kim SC. Bisphosphonates and risk of subtrochanteric, femoral shaft, and atypical femur fracture: a systematic review and meta- analysis. J Bone Miner Res. 2013 Aug;28(8):1729-37. Review. PMID: https://www.ncbi.nlm.nih.gov/pubmed/23408697 Free PMC Article
- ↑ Schilcher J et al. Bisphosphonate use and atypical fractures of the femoral shaft. N Engl J Med 2011 May 5; 364:1728. PMID: https://www.ncbi.nlm.nih.gov/pubmed/21542743
- ↑ Shane E, Burr D, Abrahamsen B, Adler RA et al Atypical subtrochanteric and diaphyseal femoral fractures: second report of a task force of the American Society for Bone and Mineral Research. J Bone Miner Res. 2014 Jan;29(1):1-23. Review. PMID: https://www.ncbi.nlm.nih.gov/pubmed/23712442 Free Article
- ↑ Tan SH, Saseendar S, Tan BH, Pawaskar A, Kumar VP. Ulnar fractures with bisphosphonate therapy: a systematic review of published case reports. Osteoporos Int. 2015 Feb;26(2):421-9. Review. PMID: https://www.ncbi.nlm.nih.gov/pubmed/25227921
- ↑ Jump up to: 34.0 34.1 Geriatric Review Syllabus, 10th edition (GRS10) Harper GM, Lyons WL, Potter JF (eds) American Geriatrics Society, 2019
- ↑ Jump up to: 35.0 35.1 35.2 Black DM et al. Atypical femur fracture risk versus fragility fracture prevention with bisphosphonates. N Engl J Med 2020 Aug 20; 383:743. PMID: https://www.ncbi.nlm.nih.gov/pubmed/32813950 https://www.nejm.org/doi/10.1056/NEJMoa1916525
- ↑ Jump up to: 36.0 36.1 He B, Etminan M, Darwich R, Eadie B. Risk of glaucoma with bisphosphonate use in patients with osteoporosis: a case-control study. Eye (Lond). 2024 Dec 27. PMID: https://www.ncbi.nlm.nih.gov/pubmed/39730976 https://www.nature.com/articles/s41433-024-03574-4.epdf