Common Questions
What are potential side effects of bisphosphonates?
Esophageal erosions. Oral bisphosphonates are absolutely contraindicated in patients with impaired esophageal emptying or patients who cannot sit or stand upright for 30 minutes following the dose. Most of the clinical trials of oral bisphosphonates excluded women with active upper GI symptoms because of fear of gastric or esophageal ulceration. The Fracture Intervention Study showed no difference in GI symptoms between the treatment and the placebo group (1). Post-marketing, alendronate was found to have an increased risk of esophageal and gastric erosions, with several reported cases of severe complications, including esophageal perforation.
Esophagitis seemed to be associated with taking the medication with little or no liquid, lying down after taking the medicine, continuation of medication with symptoms, or pre-existing esophageal problems (2).
The bottom line: When patients are appropriately screened and when taken as directed, GI complications with bisphosphonates should be minimal.
Osteonecrosis of the jaw. This is an uncommon complication (>2000 cases reported) and symptoms include jaw numbness, pain or swelling, loose teeth and exposed bone (3). The majority of cases have occurred in patients with multiple myeloma or metastatic cancer who were receiving intravenous bisphosphonates and underwent some type of dental surgery (4). The prevalence of osteonecrosis of the jaw is approximately 6-10% in cancer patients taking bisphosphonates. There have been case reports of this occurring in patients taking oral bisphosphonates.
Pain syndrome. Severe muscle, bone and joint pain have been reported in patients taking oral bisphosphonates (5). The pain can be localized initially, but then can become diffuse. Some individuals were so disabled that they became bedridden. The median time of onset after starting alendronate was 14 days. The majority of patients had gradual improvement after stopping the drug, whereas some patients had immediate relief of symptoms. It is felt to be an underreported symptom most likely because of its subjective nature and that pain can often be attributed to other causes.
Symptoms associated with IV zoledronic acid. Fever, myalgias, influenza-like symptoms, headache and arthralgias are the most common symptoms occurring shortly after an infusion of zoledronic acid. Chills, bone pain, back pain, and nausea are less common. All symptoms usually resolve within 3 days and are much less pronounced with subsequent infusions. Transient rises in creatinine (>0.5 mg/dl) may occur but usually resolve within one month. Serious episodes of atrial fibrillation were more common in individuals who had received zoledronic acid (1.3%) as compared to placebo (0.5%) (6). Most of these events occurred 30 days after receiving the infusion.
- Cummings SR, Black DM, Thompson DE, et al. Effect of alendronate on risk of fracture in women with low bone density but without vertebral fractures: results from the Fracture Intervention Trial. JAMA 1998; 280: 2077-82.
- de Groen, P.C., et al. Esophagitis associated with the use of alendronate. N Engl J Med 1996; 335(14): 1016-21.
- Kuehn BM. Reports of Adverse Events from Bone drugs prompt caution. JAMA 2006; 295: 2833-36.
- Woo SB, Hellstein JW, kalmar JR. Systematic review: bisphosphonates and osteonecrosis of the jaws. Ann Intern Med 2006; 144: 753-761.
- Wysowski DK, Chang TJ. Alendronate and risedronate; reports of severe bone, joint and muscle pain. Arch Intern Med 2005; 165: 346-347.
- Black DM, Delmas PD, Eastell R, Reid IR, et al. Once-Yearly Zoledronic Acid for Treatment of Postmenopausal Osteoporosis. NEJM 2007; 356: 1809-1822.