From Mild to Serious, Common to Rare: The Adverse Events of Osteoporosis Drugs

AE:  Osteonecrosis of the Jaw (ONJ)

• The incidence of ONJ in patients taking bisphosphonates is low (between 1/10,000 and 1/100,000 patients), but it appears to occur more frequently in patients taking intravenous bisphosphonates for malignancy-which are given more frequently and at higher doses.

• Patients with poor oral health and pre-existing jawbone infections to the jawbones who are taking bisphosphonates, may be at higher risk for ONJ.

―Recommendations:
• Patients should abstain from bisphosphonates prior to invasive dental work to reduce the risk of ONJ.
• Continued oral hygiene and regular dental evaluations are critical to resolving current infections and preventing future ones.

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AE: Atypical Femur Fracture (AFF)

AFF can occur spontaneously without a preceding trauma, but its incidence in patients taking bisphosphonates is low-0.1% or less. However, the risk of fracture rises with long-term use.

High-risk patients may have:

• Taken glucocorticoid therapy in the last six months
• Low 25-hydroxyvitamin D levels
• Hydrophosatasia, an inherited disorder affecting development of bones and teeth
• Asian ancestry

―Recommendations:
• Immediate medical evaluation of any new or persistent pain of the groin or thigh.
• Discontinuation of bisphosphonates if an atypical femur fracture or stress reaction to the femur is detected.

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AEs:  Infusion-Related

Intravenous bisphosphonates are associated with infusion-related adverse events, such as arthralgia, muscle pain and kidney complications.

―Recommendations:
• Acetaminophen can be given before infusion and for days after the infusion to reduce pain.
• Intravenous bisphosphonates, and in some cases oral doses, are not recommended in patients with chronic kidney disease (particularly when glomerular filtration rate is < 35 mL/min).

―Recommendations for managing mild adverse events:
• Mild side effects and can usually be managed with preventive measures, but there are some exceptions, such as an esophageal emptying delay, such as Barrett’s esophagitis, achalasia or stricture. In these cases, bisphosphonates should be avoided to prevent dyspepsia and esophagiitis.

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Adverse Events Associated with Oral Bisphosphonates:

―Recommendations:
• Take with a full glass of water to reduce irritation of the esophagus.
• Stay upright for 30-60 minutes.
• Intravenous zoledronic acid is an alternative therapy that may help prevent localized reactions.
• Maintain adequate levels of vitamin D and calcium to avoid hypocalcemia.

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General Principles for the Safe Use of Bisphosphonates

Most adverse events to bisphosphonate use are directly related to higher dose and longer duration of use. Bisphosphonates remain in the bone for a long period, and so adverse events due to accumulation are likely to occur. Guidelines from the United Kingdom in 2017 provided some basic principles to avoid serious complications due to bisphosphonate use.

―Recommendations:
• Review bisphosphonate treatment regularly
- Every five years for alendronate, risedronate, and ibandronate
- Every three years for zoledronic acid
• Drug holidays should be taken for patients at lower risk of fracture according to FRAX assessment.

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