The risk is best quantified and perhaps highest with bisphosphonates since they have been out the longest and thus most studied

“A nonhealing wound in the oral mucosa lasting more than 8 weeks” per JCEM 2019 – osteonecrosis of the jaw

• Risk while on bisphosphonates is thought to be around 1 in 10,000 to 100,000.
• Risk increases with longer duration of bisphosphonates.
  • After more than 4 years of therapy, risk may be as high as 21 in 10,000 (or 1 in 476)
• Risk is likely highest with an invasive dental procedure like extraction or implantation
  • Risk of ONJ after a tooth extraction while on bisphosphonate is about 1 in 200
• ONJ is more frequent in patients also with other risk factors: cancer, chemotherapy, radiation, antiangiogenic therapies

• More reading: ASBMR Task Force

Defined as insufficiency fractures of the femoral shaft defined based on radiographic criteria and low trauma (JCEM 2019 – Atypical femur fractures)

• Pathogenesis is not well understood
• The incidence of AFFs as proportion of all hip fractures is very low (~3/1000)
• The risk likely increases with longer duration of bisphosphonate therapy
• More reading: ASBMR Task Force

A 2014 Canadian study Bisphosphonates for the treatment of osteoporosis quantified the risk of developing a major osteoporotic fracture in women by risk:

Low risk: 650 / 100,000 person years
Moderate risk: 1600
High risk: 3100
ONJ risk: 1.03
AFF risk (2 years): 2

A NEJM study showed the risk of AFF is very low and rapidly decreases after bisphosphonate discontinuation:

• Within three months: 4.5/10,000
• 3-15 months: 1.8/10,000
• 15-48 months: 0.6/10,000
• 48+ months: 0.5/10,000