Bisphosphonates: neridronate (Nerixia ®), pamidronate (Aredia ®), etc.

There are several reports of the usefulness of bisphosphonates in small groups of patients with complex regional pain syndrome (CRPS). Neridronate (which is not available in the United States at the time of this writing) was studied in 40 adults with CRPS in a double blinded placebo fashion (later 36 of the patients treated with placebo were treated with neridronate) and it was found to be beneficial for up to a year. Surprisingly, there is also good initial response in those treated with placebo. One limitation to this study was that they did not include patients who had had CRPS for longer than four months. A systematic review found strong evidence for the use of bisphosphonates in the short term but there been no long-term studies. There are some serious possible side effects including osteonecrosis of the jaw (death of the jaw bone) and optic neuritis and uveitis (inflammation of the eye).

One child with CRPS was given 11 treatments of pamidronate over two years along with physical therapy and did well. Further studies need to be done before this can be recommended, particularly in children. Bisphosphonates are in bones long-term, which raises concerns about long-term effects in children.

There are no studies of bisphosphonates in diffuse amplified pain syndromes, such as fibromyalgia.

Some possible side effects are:

  • Muscle and joint pain
  • Fever
  • Tetany (low calcium levels)
  • Osteonecrosis of the jaw (death of the jaw bone)
  • Uveitis (inflammation of the eye)
  • Cardiac arrhythmia


  1. Simm PJ, Briody J, McQuade M, Munns CF. The successful use of pamidronate in an 11-year-old girl with complex regional pain syndrome: response to treatment demonstrated by serial peripheral quantitative computerised tomographic scans. Bone 2010;46:885-8.
  2. Varenna M, Adami S, Rossini M, et al. Treatment of complex regional pain syndrome type I with neridronate: a randomized, double-blind, placebo-controlled study. Rheumatology 2013;52:534-42.
  3. Bittner T, Lorbeer N, Reuther T, et al. Hemimandibulectomy after bisphosphonate treatment for complex regional pain syndrome: a case report and review on the prevention and treatment of bisphosphonate-related osteonecrosis of the jaw. Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology 2012;113:41-7.
  4. Stack R, Tarr K. Drug-induced optic neuritis and uveitis secondary to bisphosphonates. New Zealand Medical Journal 2006;119:U1888.

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