A market analysis shows that bisphosphonates will reach $14 billion in sales by 2021. As more patients are prescribed these osteoporosis drugs, physicians will increasingly be faced with managing drug-related adverse events. Learn more in this article.
A market analysis by Zion Market Research shows that bisphosphonates will reach $14 billion in sales by 2021. This is, in part, due to an burgeoning aging population. These first-line agents currently make up about 48 percent of the total osteoporosis drugs market. As more patients are prescribed bisphosphonates, physicians will increasingly be faced with managing drug-related adverse events from mild to serious to common and rare. Learn more in this article.
Compston J, Cooper A, Cooper C, et al. UK clinical guideline for the prevention and treatment of osteoporosis. Arch Osteoporos 2017;12:43. https://www.ncbi.nlm.nih.gov/pubmed/28425085Eleutherakis-Papaiakovou E, Bamias A. Antiresorptive treatment-associated ONJ. Abstract. Eur J Cancer Care (Engl). 2017;26(6). https://www.ncbi.nlm.nih.gov/pubmed/29063702Fassio A, Bertoldo F, Idolazzi L, et al. Drug-induced osteonecrosis of the jaw: the state of the art. Abstract. Reumatismo 2017;69:9-15. https://www.ncbi.nlm.nih.gov/pubmed/28535616Jagpal A, Saag KG. How to use bisphosphonates safely and optimally. Rheumatology (Oxford). 2018;57:1875-1876. https://www.ncbi.nlm.nih.gov/pubmed/29165674
Adverse Events Associated with Intravenous Bisphosphonates:
Bisphosphonates work by suppressing the resorption of bone tissue, however, they have been associated with some adverse effects (some rare, others more common), including:
• Osteonecrosis of the jaw
• Atypical femur fracture
• Delays in fracture healing
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.
• 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.
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
• 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.
Intravenous bisphosphonates are associated with infusion-related adverse events, such as arthralgia, muscle pain and kidney complications.
• 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).
âRecommendations 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.
Adverse Events Associated with Oral Bisphosphonates:
• 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.
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.
• 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.