Editing Bisphosphonate (section)

==Medical uses==
Bisphosphonates are used to treat osteoporosis, [[osteitis deformans]] (Paget's disease of the bone), bone [[metastasis]] (with or without hypercalcemia), multiple myeloma, and other conditions involving fragile, breakable bone.

In osteoporosis and Paget's, the most popular first-line bisphosphonate drugs are [[alendronate]] and [[risedronate]]. If these are ineffective or if the person develops digestive tract problems, intravenous [[pamidronate]] may be used. [[Strontium ranelate]] or [[teriparatide]] are used for refractory disease. The use of strontium ranelate is restricted  because of increased risk of [[venous thromboembolism]], [[pulmonary embolism]] and serious cardiovascular disorders, including [[myocardial infarction]].<ref>{{cite web|title=Strontium ranelate: cardiovascular risk—restricted indication and new monitoring requirements Article date: March 2014|url=http://www.mhra.gov.uk/Safetyinformation/DrugSafetyUpdate/CON392870|publisher=MHRA}}</ref> In postmenopausal women, the [[selective estrogen receptor modulator]] [[raloxifene]] is occasionally administered instead of bisphosphonates. Bisphosphonates are beneficial in reducing the risk of [[vertebral fracture]] in [[steroid induced osteoporosis]].<ref>{{cite journal|last1=Allen|first1=CS|last2=Yeung|first2=JH|last3=Vandermeer|first3=B|last4=Homik|first4=J|title=Bisphosphonates for steroid-induced osteoporosis.|journal=The Cochrane Database of Systematic Reviews|date=5 October 2016|volume=2016|issue=10|pages=CD001347|pmid=27706804|doi=10.1002/14651858.CD001347.pub2|pmc=6461188}}</ref>

===Post-menopausal osteoporosis===
Bisphosphonates are recommended as a first line treatments for post-menopausal osteoporosis.<ref name=AACE2010>{{cite journal | pmid = 21224201 | pmc=4876714 | volume=16 | title=American Association of Clinical Endocrinologists Medical Guidelines for Clinical Practice for the diagnosis and treatment of postmenopausal osteoporosis | year=2010 | journal=Endocr Pract | pages=1–37 |vauthors=Watts NB, Bilezikian JP, Camacho PM, Greenspan SL, Harris ST, Hodgson SF, Kleerekoper M, Luckey MM, McClung MR, Pollack RP, Petak SM | issue=Suppl 3 | doi=10.4158/ep.16.s3.1}}</ref><ref>{{cite journal |title=Management of osteoporosis in postmenopausal women: 2010 position statement of The North American Menopause Society |journal=Menopause |volume=17 |issue=1 |pages=25–54; quiz 55–6 |year=2010 |pmid=20061894 |doi=10.1097/gme.0b013e3181c617e6 |s2cid=7980731}}</ref><ref>{{cite journal |author=Hauk L |title=ACOG releases practice bulletin on osteoporosis |journal=Am Fam Physician |volume=88 |issue=4 |pages=269–75 | date=August 2013|pmid=23944732 }}</ref><ref>{{cite journal |vauthors=Compston J, Bowring C, Cooper A |title=Diagnosis and management of osteoporosis in postmenopausal women and older men in the UK: National Osteoporosis Guideline Group (NOGG) update 2013 |journal=Maturitas |volume=75 |issue=4 |pages=392–6 | date=August 2013|pmid=23810490 |doi=10.1016/j.maturitas.2013.05.013 |display-authors=etal|doi-access=free }}</ref>

Long-term treatment with bisphosphonates produces anti-fracture and bone mineral density effects that persist for 3–5 years after an initial 3–5 years of treatment.<ref name="Eriksen EF, Díez-Pérez A, Boonen S 126–35"/> The bisphosphonate alendronate  reduces the risk of hip, vertebral, and wrist fractures by 35-39%; zoledronate reduces the risk of hip fractures by 38% and of vertebral fractures by 62%.<ref name="Serrano AJ, Begoña L, Anitua E, Cobos R, Orive G 1005–14"/><ref name="gauthier"/> Risedronate has also been shown to reduce the risk of hip fractures.<ref name=AACE2010/><ref name="Kanis JA, McCloskey EV, Johansson H, Cooper C, Rizzoli R, Reginster JY 23–57"/>

After five years of medications by mouth or three years of intravenous medication among those at low risk, bisphosphonate treatment can be stopped.<ref name=Ad2016/> In those at higher risk ten years of medication by mouth or six years of intravenous treatment may be used.<ref name=Ad2016>{{cite journal|last1=Adler|first1=Robert A|last2=El-Hajj Fuleihan|first2=Ghada|last3=Bauer|first3=Douglas C|last4=Camacho|first4=Pauline M|last5=Clarke|first5=Bart L|last6=Clines|first6=Gregory A|last7=Compston|first7=Juliet E|last8=Drake|first8=Matthew T|last9=Edwards|first9=Beatrice J|last10=Favus|first10=Murray J|last11=Greenspan|first11=Susan L|last12=McKinney|first12=Ross|last13=Pignolo|first13=Robert J|last14=Sellmeyer|first14=Deborah E|title=Managing Osteoporosis in Patients on Long-Term Bisphosphonate Treatment: Report of a Task Force of the American Society for Bone and Mineral Research|journal=Journal of Bone and Mineral Research|date=January 2016|volume=31|issue=1|pages=16–35|doi=10.1002/jbmr.2708|pmid=26350171|pmc=4906542}}</ref>

===Cancer===
Bisphosphonates reduce the risk of fracture and bone pain<ref>{{cite journal |vauthors=Zhu M, Liang R, Pan LH |title=Zoledronate for metastatic bone disease and pain: a meta-analysis of randomized clinical trials |journal=Pain Med |volume=14 |issue=2 |pages=257–64 | date=February 2013|pmid=23279447 |doi=10.1111/pme.12016 |display-authors=etal|doi-access=free }}</ref> in people with breast,<ref name=OCarrigan2017>{{Cite journal|last1=O'Carrigan|first1=Brent|last2=Wong|first2=Matthew Hf|last3=Willson|first3=Melina L.|last4=Stockler|first4=Martin R.|last5=Pavlakis|first5=Nick|last6=Goodwin|first6=Annabel|date=2017|title=Bisphosphonates and other bone agents for breast cancer|journal=The Cochrane Database of Systematic Reviews|volume=10|issue=11|pages=CD003474|doi=10.1002/14651858.CD003474.pub4|issn=1469-493X|pmid=29082518|pmc=6485886}}</ref> lung,<ref>{{cite journal |vauthors=Lopez-Olivo MA, Shah NA, Pratt G, Risser JM, Symanski E, Suarez-Almazor ME |title=Bisphosphonates in the treatment of patients with lung cancer and metastatic bone disease: a systematic review and meta-analysis |journal=Support Care Cancer |volume=20 |issue=11 |pages=2985–98 | date=November 2012|pmid=22956190 |pmc=3691019 |doi=10.1007/s00520-012-1563-z }}</ref> and other metastatic cancers as well as in people with multiple myeloma.<ref>{{cite journal |vauthors=Mhaskar R, Kumar A, Miladinovic B, Djulbegovic B |title=Bisphosphonates in multiple myeloma: a network meta-analysis |journal=Cochrane Database Syst Rev |volume= 2017|pages=CD003188 |year=2017 |issue=12 |pmid=29253322|doi=10.1002/14651858.CD003188.pub4 |pmc=6486151 }}</ref> In breast cancer there is mixed evidence regarding whether bisphosphonates improve survival.<ref name=OCarrigan2017 /><ref>{{cite journal |vauthors=Ben-Aharon I, Vidal L, Rizel S |title=Bisphosphonates in the adjuvant setting of breast cancer therapy--effect on survival: a systematic review and meta-analysis |journal=PLOS ONE |volume=8 |issue=8 |pages=e70044 |year=2013 |pmid=23990894 |pmc=3753308 |doi=10.1371/journal.pone.0070044 |bibcode=2013PLoSO...870044B |display-authors=etal|doi-access=free }}</ref><ref>{{cite journal |vauthors=Zhu J, Zheng Y, Zhou Z |title=Oral adjuvant clodronate therapy could improve overall survival in early breast cancer: results from an updated systematic review and meta-analysis |journal=Eur. J. Cancer |volume=49 |issue=9 |pages=2086–92 | date=June 2013|pmid=23452992 |doi=10.1016/j.ejca.2013.01.021 }}</ref><ref name=VanAcker2015 /> A 2017 Cochrane review found that for people with early breast cancer, bisphosphonate treatment may reduce the risk of the cancer spreading to the person's bone, however, for people who had advanced breast cancer bisphosphonate treatment did not appear to reduce the risk of the cancer spreading to the bone.<ref name=OCarrigan2017 /> Side effects associated with bisphosphonate treatment for people with breast cancer are mild and rare.<ref name=OCarrigan2017 />

Bisphosphonates can also reduce mortality in those with multiple myeloma and prostate cancer.<ref name=VanAcker2015>{{cite journal|last1=Van Acker|first1=HH|last2=Anguille|first2=S|last3=Willemen|first3=Y|last4=Smits|first4=EL|last5=Van Tendeloo|first5=VF|title=Bisphosphonates for cancer treatment: Mechanisms of action and lessons from clinical trials.|journal=Pharmacology & Therapeutics|date=23 November 2015|pmid=26617219|doi=10.1016/j.pharmthera.2015.11.008|volume=158|pages=24–40}}</ref>

===Other===
Evidence suggests that the use of bisphosphonates would be useful in the treatment of [[complex regional pain syndrome]], a neuro-immune problem with high MPQ scores, low treatment efficacy and symptoms which can include regional osteoporosis. In 2009  bisphosphonates were "among the only class of medications that has survived placebo-controlled studies showing statistically significant improvement (in CRPS) with therapy."<ref>{{cite journal |author=Pontell D |title=A clinical approach to complex regional pain syndrome |journal=Clinics in Podiatric Medicine and Surgery |volume=25 |issue=3 |pages=361–80; vi |date=July 2008  |pmid=18486850 |doi=10.1016/j.cpm.2008.02.011}}</ref>

There is observational evidence and molecular explanation for some bisphosphonates offering a level of protection against [[COVID-19]].<ref>{{cite journal |author=Thompson J |title=Association between Bisphosphonate use and COVID-19 related outcomes |journal=eLife |volume=12 |pages=e79548 |date=2023 |doi=10.7554/eLife.79548|doi-access=free |pmid=37534876 |pmc=10691801 }}</ref><ref>{{cite journal |author=Muzaffar-Ur-Rehman M |title=In silico evaluation of bisphosphonates identifies leading candidates for SARS-CoV-2 RdRp inhibition |journal=Journal of Molecular Graphics and Modelling |volume=136 |pages=108939 |date=May 2025|doi=10.1016/j.jmgm.2024.108939|pmid=39799876 |doi-access=free }}</ref>

Bisphosphonates have been used to reduce fracture rates in children with the disease [[osteogenesis imperfecta]]<ref>{{cite journal |vauthors=Shapiro JR, Sponsellor PD |title=Osteogenesis imperfecta: questions and answers |journal=Current Opinion in Pediatrics |volume=21 |issue=6 |pages=709–16 |date=December 2009 |pmid=19907330 |doi=10.1097/MOP.0b013e328332c68f |s2cid=205834462 }}</ref> and to treat [[otosclerosis]]<ref>{{cite journal |author=Brookler K |title=Medical treatment of otosclerosis: rationale for use of bisphosphonates |journal=Int Tinnitus J |volume=14 |issue=2 |pages=92–6 |year=2008 |pmid=19205157 }}</ref> by minimizing bone loss.

Other bisphosphonates, including [[medronate]] (R<sup>1</sup>=H, R<sup>2</sup>=H) and [[oxidronate]] (R<sup>1</sup>=H, R<sup>2</sup>=OH), are mixed with radioactive [[technetium]] and injected, as a way to image bone and detect bone disease.