Published: 6 September 2013

Joint Swelling Associated with Zoledronate and Pamidronate

Prescriber Update 34(3):29
September 2013

The Centre for Adverse Reactions Monitoring (CARM) has received a total of 16 reports of joint swelling reactions associated with zoledronate and pamidronate. Eleven of these reports have been received since the beginning of 2012. This represents a substantial increase in reporting of these reactions.

Cases of joint swelling, particularly synovitis, associated with alendronate have been reported to CARM and highlighted previously1. Joint swelling may occur as part of a severe acute phase-like response (reaction). Symptoms of an acute phase response generally include fever and influenza–like symptoms, joint, bone and muscle pains, and fatigue.

Changes in inflammatory markers have been noted in patients experiencing acute phase-like reactions to bisphosphonates. These changes include an increase in C-reactive protein, transient decrease in white cell count, increase in interleukin-6 and increase in TNF-alpha. Acute phase reactions have only been associated with aminobisphosphonates (ie, not with etidronate).

Of the 16 reports received by CARM, four reports were associated with pamidronate (5% of the total pamidronate reports) and 12 reports with zoledronate (7% of the total zoledronate reports).

In ten of the cases, the patient was reported to have experienced influenza-like symptoms (seven cases) or to have had a positive C-reactive protein test (three cases). This suggests that these cases are consistent with an acute phase-like reaction.

In the cases reported to CARM, onset of symptoms was within 24 hours in eight of the cases and within seven days for the remaining cases.

Most patients are expected to recover, usually within two to four weeks. Some patients will have a recurrence of symptoms with the next infusion or with treatment with an alternative aminobisphosphonate.

  1. Savage R. 2006. Alendronate and inflammatory adverse reactions. Prescriber Update 27(1): 4–6. URL: (accessed 2 August 2013).