Editing Bisphosphonate (section)

===Long-term risks===
In large studies, women taking bisphosphonates for osteoporosis have had unusual fractures ("bisphosphonate fractures") in the [[femur]] (thigh bone) in the shaft ([[diaphysis]] or [[Human trochanter|sub-trochanteric]] region) of the bone, rather than at the femoral neck, which is the most common site of fracture. However, these fractures are rare (12 in 14,195 women) compared to the common hip fractures (272 in 14,195 women), and the overall reduction in hip fractures caused by bisphosphonate is more than the increase in unusual shaft fractures.<ref name="Shane">{{cite journal |author=Shane E |title=Evolving data about subtrochanteric fractures and bisphosphonates |journal=N. Engl. J. Med. |volume=362 |issue=19 |pages=1825–7 |date=May 2010 |pmid=20335574 |doi=10.1056/NEJMe1003064 }}</ref>{{Obsolete source|reason=Needs a more recent secondary source summarizing recent studies.|date=April 2019}} There are concerns that long-term bisphosphonate use can result in over-suppression of [[bone turnover]]. It is hypothesized that micro-cracks in the bone are unable to heal and eventually unite and propagate, resulting in atypical fractures. Such fractures tend to heal poorly and often require some form of bone stimulation, for example [[bone grafting]] as a secondary procedure. This complication is not common, and the benefit of overall fracture reduction still holds.<ref name="Shane"/><ref>{{cite journal |vauthors=Lenart BA, Lorich DG, Lane JM |title=Atypical fractures of the femoral diaphysis in postmenopausal women taking alendronate |journal=N. Engl. J. Med. |volume=358 |issue=12 |pages=1304–6 |date=March 2008 |pmid=18354114 |doi=10.1056/NEJMc0707493 |doi-access=free }}</ref>{{npsn|date=April 2019}} In cases where there is concern of such fractures occurring, [[teriparatide]] is potentially a good alternative because it does not cause as much damage as a bisphosphonate does by suppressing bone turnover.<ref name=Arkan>{{cite journal|author2=Bakir K Kadum|author3=Göran O Sjödén|title=Bisphosphonate-induced femoral fragility fractures: What do we know?|journal=Orthopedic Research and Reviews|date=31 March 2010|volume=2|issue=1|pages=27–34|doi=10.2147/orr.s7521|author=Arkan S Sayed-Noor|doi-access=free}}</ref>

Three meta analyses have evaluated whether bisphosphonate use is associated with an increased risk of esophageal cancer.  Two studies concluded that there was no evidence of increased risk.<ref>{{cite journal |vauthors=Andrici J, Tio M, Eslick GD |title=Meta-analysis: oral bisphosphonates and the risk of oesophageal cancer |journal=Aliment. Pharmacol. Ther. |volume=36 |issue=8 |pages=708–16 | date=October 2012|pmid=22966908 |doi=10.1111/apt.12041 |s2cid=5271005 |doi-access=free }}</ref><ref>{{cite journal |vauthors=Sun K, Liu JM, Sun HX, Lu N, Ning G |title=Bisphosphonate treatment and risk of esophageal cancer: a meta-analysis of observational studies |journal=Osteoporos Int |volume=24 |issue=1 |pages=279–86 | date=January 2013|pmid=23052941 |doi=10.1007/s00198-012-2158-8 |s2cid=12625687 }}</ref><ref>{{cite journal |vauthors=Oh YH, Yoon C, Park SM |title=Bisphosphonate use and gastrointestinal tract cancer risk: meta-analysis of observational studies |journal=World J. Gastroenterol. |volume=18 |issue=40 |pages=5779–88 | date=October 2012|pmid=23155320 |pmc=3484348 |doi=10.3748/wjg.v18.i40.5779 |doi-access=free }}</ref>