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Treatment after development of acute phase reaction due to zoledronic acid infusion is generally limited to supportive care and/or nonsteroidal anti-inflammatory drugs (NSAIDs) acetaminophen or dexamethasone, largely based on extrapolation of the noted preventive trials and expert opinion.3,6 Experiencing an acute phase reaction may portend better fracture risk reduction from zoledronic acid, although there is a potential association between acute phase reaction and mortality risk.23,24
Our case was typical for acute phase reaction to zoledronic acid. The patient was already taking rosuvastatin 10 mg daily for hypercholesterolemia as prescribed by his primary care physician. Rosuvastatin was not shown to prevent symptoms, although it was not studied in patients on long-term statin therapy at the time of zoledronic acid infusion.18 The patient was also taking vitamin D3 supplementation and was nearly in the reference range.5 His ED treatment included IV fluids and acetaminophen. Pretreatment (prior to or at the time of zoledronic acid infusion) with acetaminophen or ibuprofen may have prevented his symptoms, or at least lessened them to the point that an ED visit would not have resulted. The endocrinologist who prescribed the zoledronic acid documented a detailed discussion of the adverse effects of zoledronic acid with the patient, and the initial nursing call documents consideration of acute phase reaction. It is unclear whether the persistence of symptoms or worsening of symptoms ultimately led to the ED visit. Because no treatment was offered, it is unknown whether earlier posttreatment with acetaminophen, ibuprofen, or dexamethasone might have prevented his ED visit.
Conclusions
Clinicians who treat patients with osteoporosis should be aware of several key points. First, acute phase reaction symptoms are common with bisphosphonates, especially zoledronic acid infusions. Second, the symptoms are nonspecific but should have a suggestive time course. Third, dexamethasone may be partially protective, but based on the various trials discussed, it likely needs to be given for multiple days (instead of a single dose on the day of infusion). Given that acetaminophen and NSAIDs also seem to be protective (when given for multiple days starting on the day of infusion), both have lower overall adverse effect profiles than dexamethasone, consideration may be given to using either of these prophylactically.6 Dexamethasone could then be prescribed if symptoms are severe or persistent despite the use of acetaminophen or NSAIDs.
