Significance and impact of bisphosphonate-induced acute phase responses

Bisphosphonates are synthetic analogs of inorganic pyrophosphates with high avidity for bone, where they bind to hydroxyapatite crystals. Bisphosphonates are effective in decreasing bone resorption, the incidence of skeletal-related events, and pain from bone metastases. These agents have recently become incorporated into the treatment regimen of patients with osteolytic and osteoblastic metastatic bone disease. Although relatively well tolerated, the initial dose(s) of intravenous aminobisphosphonates can be associated with an acute phase response, a nonspecific physiologic reaction associated with increased levels of inflammatory cytokines, fever, and flu like symptoms including fatigue, nausea, and myalgia.

The purpose of this article is to provide an updated review of the literature in this field.

A search of PubMed was performed using the key terms bisphosphonate, acute phase response, and cancer, and limited to publications in English. The published literature on acute phase response with bisphosphonate therapy was reviewed.

Approximately 40% of patients receiving aminobisphosphonates experience an acute phase response, which generally occurs only on first exposure to the drug and typically last <72 h. Not all bisphosphonates induce acute phase responses to the same extent. This article reviews acute phase response in patients with metastatic bone disease treated with aminobisphosphonates.