Pamidronate infusion for CRPS was linked to modest, short-term pain relief in a 2026 Erasmus MC study of 97 patients. Average pain fell from 7.95 to 6.86 out of 10 one month after treatment. By 6 and 12 months, the drop was no longer clear.
Complex regional pain syndrome (CRPS) causes pain, touch sensitivity and changes in an affected limb. A 2025 review of 11 trials found that bisphosphonates, the drug group that includes pamidronate, lowered pain between 1 and 3 months after treatment. The authors rated that evidence as low certainty. This article is educational and does not replace a medical assessment.
What is CRPS?
CRPS affects an arm, hand, leg or foot, usually after an injury or surgery. The pain is stronger and lasts longer than the original injury explains. Symptoms include swelling, skin colour or temperature changes, unusual sweating, stiffness and reduced movement. The mix of symptoms differs from person to person.
The Erasmus MC study team reports that CRPS develops in about 6.5% of high-risk people, such as patients after a fracture or surgery, within 24 months. Symptoms often ease in the first 6 months, but full recovery is uncommon.
Allodynia means pain from contact that does not normally hurt, such as clothing touching the skin. Hyperalgesia means a stronger pain response to something that already hurts.
CRPS type 1 occurs without a confirmed major nerve injury. Type 2 involves a defined nerve injury. Doctors use the Budapest criteria, a set of symptom and examination rules, and check for other causes. No single blood test or scan confirms CRPS.
What is pamidronate?
Pamidronate is a bisphosphonate that slows bone breakdown. A clinician gives it through an intravenous (IV) drip, a small tube in a vein. Its Canadian product monograph lists certain bone conditions and cancer-related high blood calcium. It does not list CRPS.
Use for CRPS is off-label: the medicine is prescribed for a condition outside its listed uses. A prescriber weighs the evidence, risks and other treatment choices. The Erasmus MC study could not identify which patients benefit most.
What did the main Erasmus MC study find?
According to Erasmus MC research from the Department of Anesthesiology, published on February 18, 2026, van der Spek and colleagues reviewed the records of 97 adults treated between June 2014 and June 2024. The clinic's plan was 60 mg of IV pamidronate once a month for 3 months. Of the 97 patients, 88 (91%) finished all 3 infusions.
Seventy percent had persistent CRPS, meaning symptoms lasted more than 12 months. The group was 88% women, with a median age of 45 and a median disease length of 31 months. Ninety-two percent had CRPS type 1.
Average pain fell from 7.95 to 6.49 out of 10 during treatment. The drop was 1.10 points at 1 month and 0.66 points at 3 months. At 6 and 12 months, the change may have been chance. A responder had pain fall by 2 or more points: 34% at 1 month and 22% at 3 months. The chart below shows each time point.
The authors concluded that pamidronate was well tolerated and linked to modest, short-term pain relief in mostly persistent CRPS. They rated the overall benefit in persistent CRPS as limited. The study had no placebo group. At 12 months, only 35 of 97 patients were still being followed, and 17 of them had a pain score recorded.
- Clear drop from the start
- Change may be chance
| Time point | Average pain (0 to 10) | Change from start | Responders |
|---|---|---|---|
| Start of treatment | 7.95 | n/a | n/a |
| During treatment | 6.49 | −1.46 | 40% (39 of 97) |
| 1 month after | 6.86 | −1.10 | 34% (33 of 96) |
| 3 months after | 7.29 | −0.66 | 22% (19 of 87) |
| 6 months after | 7.49 | −0.47 (may be chance) | 16% (11 of 68) |
| 12 months after | 7.37 | −0.59 (may be chance) | 23% (8 of 35) |
A responder had pain fall by 2 or more points. When paired pain scores were missing, the study counted the patient's own report of benefit.
Fewer patients had follow-up data over time. At 12 months, 35 of 97 patients were still being followed, and 17 had a pain score. Later results are less certain.
Source: van der Spek DPC, Huygen FJPM, Hoeks SE, van Daele PLA, Dirckx M. Intravenous Pamidronate in Persistent Complex Regional Pain Syndrome (CRPS). Journal of Pain Research. 2026;19:573167. Erasmus MC, Department of Anesthesiology. Numbers from Tables 2 and 3; chart redrawn by Solis Medical Clinic.
Why did other studies find bigger effects?
The Erasmus MC team compared their results with earlier studies. A 2025 study from the Department of Rheumatology at Amiens-Picardie University Hospital in France reviewed 255 patient records and reported response in 67.1% at 4 months. In that study, patients with swelling at the start were more likely to respond. Amiens counted fewer CRPS signs, not lower pain scores, so its rate does not compare directly with the Erasmus results. Its patients had symptoms for about 2 years on average.
In most earlier studies, treatment started within 6 months of CRPS onset. The Erasmus authors suggest that pamidronate acts on active inflammation, which fades as CRPS lasts longer. In their group, 70% had CRPS for more than a year, and pain relief was smaller and shorter. They also note that some earlier studies added physiotherapy at the same time, which makes the drug's own effect harder to measure, and that their own careful handling of missing data may have lowered their numbers.
What do placebo-controlled trials show?
Two sources compare bisphosphonates with a placebo: one small pamidronate trial and a review of 11 trials.
Burwood Hospital placebo-controlled trial, 2004
According to research from the Pain Management Centre at Burwood Hospital in Christchurch, New Zealand, published in September 2004, Robinson and colleagues compared one 60 mg pamidronate dose with a saline placebo. The trial included 27 adults with CRPS type 1: 14 received pamidronate and 13 received placebo.
At 3 months, the pamidronate group had better pain, disease severity and physical function scores. No pain benefit appeared at 1 month. With 27 patients, the trial is too small to predict one person's result.
Bisphosphonate review, 2025
According to a review led by the University of New South Wales, published in Annals of Internal Medicine on December 16, 2025, Ferraro and colleagues pooled 11 placebo-controlled trials with 754 participants. Only 1 trial tested pamidronate, and 97% of participants had CRPS type 1.
In the first 4 weeks, there was little to no clear difference from placebo. Between 1 and 3 months, bisphosphonates lowered pain 10 points more than placebo on a 100-point scale. The authors rated this evidence as low certainty. Results after 3 months were uncertain. Side effects were 1.1 times as common as with placebo. These results apply to the drug group, not to pamidronate alone.
Study results at a glance
The Erasmus MC study shows routine care in long-lasting CRPS. The 2004 trial is the only pamidronate study here with a placebo group, but it had 27 patients.
| Reported measure | Erasmus MC, 2026 | Burwood Hospital, 2004 |
|---|---|---|
| Participants | 97 adults; 70% had persistent CRPS | 27 adults with CRPS type 1 |
| Study design | Review of medical records | Randomized trial with a saline placebo |
| Pamidronate dose | 60 mg once a month for 3 months (planned) | One 60 mg dose |
| Result at 1 month | Pain down 1.10 points; 34% responded | No pain benefit over placebo |
| Result at 3 months | Pain down 0.66 points; 22% responded | Better pain, disease severity and function scores than placebo |
| Placebo comparison | None | Yes, 13 patients |
Source: van der Spek et al. Intravenous Pamidronate in Persistent CRPS. Journal of Pain Research. 2026;19:573167. Erasmus MC, Department of Anesthesiology. Tables 1 to 3.
Source: Robinson et al. Efficacy of pamidronate in complex regional pain syndrome type I. Pain Medicine. 2004;5:276-280. Pain Management Centre, Burwood Hospital, Christchurch, New Zealand.
What do these findings mean for patients?
Pamidronate gave the clearest benefit in the first 3 months. In long-lasting CRPS, the Erasmus MC study found smaller and shorter relief. Trials in earlier CRPS, mostly using other bisphosphonates such as neridronate, reported bigger effects.
The Erasmus MC study reviewed existing records. Without an untreated group, it cannot separate the drug's effect from other care or recovery over time. The percentages describe that study group, not one person's chance of success.
How was pamidronate given in the studies?
The 2004 trial used one 60 mg infusion. The Erasmus MC study used 60 mg over 4 hours, once a month for 3 months. The Amiens study used several schedules, most often three 90 mg infusions a month apart. No single CRPS dose is standard.
These are research protocols, not a treatment order. The treating physician sets the dose, drip rate, number of visits and monitoring.
How long does the infusion take?
Each Erasmus MC infusion took 4 hours. The full visit also includes checks before the drip and monitoring after it.
Ask for the total visit time and who to contact if symptoms start at home. Arrange a ride if your care team advises it. Do not drive if treatment leaves you dizzy or sleepy.
What are the side effects and safety checks?
The Canadian product monograph lists fever, flu-like symptoms, tiredness, headache, nausea and low blood calcium. Serious risks include kidney injury, severe allergic reactions and jaw bone damage.
In the Erasmus MC study, 88 of 97 patients (91%) had at least one side effect. A flu-like reaction after the drip was the most common, at 63%. Six patients (6%) stopped early because of side effects. No patient developed jaw bone damage.
Before infusion, the Erasmus MC team tested kidney function (creatinine) and calcium. If dental health was in doubt, a dentist or oral surgeon checked the patient first. Staff checked blood pressure and oxygen levels before and after the drip.
Before treatment, discuss kidney function, calcium and vitamin D status, dental problems, planned dental surgery, allergies and all medicines. The monograph lists pregnancy and breastfeeding as contraindications, meaning reasons not to give the drug. Your clinician decides which tests your case requires.
| Side effect | Patients (out of 97) | Share of patients |
|---|---|---|
| Flu-like reaction after the drip (acute phase reaction) | 61 | 63% |
| Pain or a reaction where the drip went in | 32 | 33% |
| Muscle aches | 25 | 26% |
| Sore, irritated vein (phlebitis) | 25 | 26% |
| Headache | 19 | 20% |
| Nausea or vomiting | 16 | 16% |
| Low blood calcium | 15 | 15% |
| Jaw bone damage (osteonecrosis of the jaw) | 0 | 0% |
Source: van der Spek et al. Intravenous Pamidronate in Persistent CRPS. Journal of Pain Research. 2026;19:573167. Erasmus MC, Department of Anesthesiology. Table 4. A patient could have more than one side effect.
Where does pamidronate fit in CRPS care?
According to the 5th edition CRPS treatment guidelines, published in 2022 by an international team led by Harden from Northwestern University, CRPS care centres on restoring function. Physical and occupational therapy address movement, sensitivity and daily tasks. Medicine is one part of that plan.
What is the best treatment for CRPS?
No single treatment cures CRPS. The 2022 guidelines combine rehabilitation, pain treatment, psychological support, education and self-management. A pamidronate infusion is one option to discuss, not a replacement for that plan.
The choice depends on the diagnosis, past treatment results and medical risks. Rehabilitation needs a pace the person can manage, because overly hard exercise can worsen symptoms. Work with a therapist experienced in CRPS.
How to track progress
Track walking, hand use, sleep and activity alongside pain. For example, record whether you can wear a shoe or finish a therapy session. Use the same task at each review so the care team can compare results.
For an assessment in Edmonton, bring your symptom timeline, medicine list and past treatment results to your usual clinician or a pain clinic.
What treatments help CRPS in the hand?
The 2022 guidelines describe desensitisation and graded motor imagery in rehabilitation. Graded motor imagery is a step-by-step program that includes mirror therapy. Desensitisation uses controlled contact with textures to reduce touch sensitivity. Mirror therapy uses the reflection of the other hand during guided movement tasks.
Hand therapy focuses on daily use: holding a cup, dressing, writing and moving the fingers. A therapist sets tasks around current movement and sensitivity. Record which tasks you can do, how long they take and what stops you.
An IV infusion does not replace hand rehabilitation. Pain relief and useful hand movement are separate goals.
Questions to ask before an infusion
- Is my diagnosis CRPS type 1 or type 2?
- What evidence supports this treatment in my case?
- What dose, tests and follow-up visits are planned?
- Which side effects should I report, and to whom?
- How will we measure benefit and decide whether to stop?
- What rehabilitation plan, alternatives, fees and coverage apply?
Find more tools in our pain management resources and reading recommendations.
Quick answers
Does pamidronate cure CRPS?
The studies do not establish a cure. They report symptom changes over set follow-up periods. Lasting benefit remains uncertain.
Does the evidence apply to CRPS type 2?
Most trial participants had CRPS type 1. The available research does not establish the same benefit for type 2.
When should the care team check whether an infusion helped?
The studies measured results over weeks and months, not just on infusion day. Agree on follow-up dates before treatment. Record pain and a specific daily task at baseline, then use the same measures at each review. Ask what result would lead the prescriber to continue, change or stop treatment.
Is pamidronate used for complex regional pain syndrome outside research?
Yes. The two hospital studies reviewed pamidronate given during routine clinical care. That use does not establish that every CRPS patient should receive it. The Canadian product monograph does not list CRPS, so treatment remains an off-label prescribing decision.
Sources and clinical guidance
- Main reference: van der Spek et al. (2026), Erasmus MC. Intravenous Pamidronate in Persistent CRPS (PDF)
- Robinson et al. (Pain Medicine, September 2004): placebo-controlled pamidronate trial
- Ferraro et al. (Annals of Internal Medicine, online December 16, 2025): bisphosphonate review
- Doussiere et al. (Scientific Reports, July 16, 2025): Amiens-Picardie study
- Pfizer Canada: pamidronate product monograph
- Harden et al. CRPS: Practical Diagnostic and Treatment Guidelines, 5th edition (Pain Medicine, 2022)