Keeping faith in bisphosphonates: Pamidronate for CRPS

As Libby Parfitt reported back in January 2018, the multiple-centre trial of a seemingly promising drug for the treatment of CRPS, Zoledronic Acid (also known as Zoledronate), was halted by the pharmaceutical company, Axsome Therapeutics. The reason given for this move was “futility”; in other words, the data collected to that point suggested that the trial was not going to meet its objectives.

As Libby said at the time: “It looked promising and many thought we might finally be on the verge of a breakthrough in actually treating CRPS as opposed to simply managing its symptoms.”

Bisphosphonates

Zoldronate is a member of a family of drugs known as bisphosphonates which, among other things, help prevent the loss of bone density and as such are commonly used in the treatment of osteoporosis. Another bisphosphonate, Neridronate, about which we have also written previously, is actively available in Italy for the treatment of CRPS.

In 2014, which of course was prior to the halting of the Zoledronate trial, a meta-analysis highlighted “that bisphosphonates should be the pharmacological agents of choice in the management of [CRPS Type I], given also the limited efficacy demonstrated by other medications.”

Pamidronate

Another member of the bisphosphonate family, Pamidronate, which more often is used to treat secondary bone cancer, continues to be used to also treat early stage CRPS.

As long ago as 2004, a small scale clinical trial concluded that “Pamidronate may be a useful treatment option in the management of patients with CRPS Type I. Although treatment response was variable, the majority of patients improved. Early administration in tandem with other treatment measures is recommended.”

In that trial it was noted that after 3 months there was an overall improvement in both pain score and physical function compared to the control group who were given a placebo. Despite these promising results, since then there have been no larger scale clinical trials of Pamidronate. However, in the UK, pain medicine consultants in some NHS Trusts are now referring patients with early stage CRPS for a Pamidronate infusion whilst maintaining their general regime of medication and physical therapy. One CRPS sufferer we spoke to recently had experienced some short term improvement in pain and function following a Pamidronate infusion, but the treatment was not repeated.

Clearly, despite the apparent failure of Zoledronate, the medical profession continue to have faith in bisphosphonates more generally as an additional therapy for early stage CRPS. Interestingly, a study in 2001 expressed cautious optimism that Pamidronate may even be effective in the treatment of established CRPS, but stressed “these results need to be confirmed by a controlled placebo study.” As seems to be a common theme here, it does not appear as though such a further study has taken place.