Role of alendronate in therapy for posttraumatic complex regional pain syndrome type I of the lower extremity

Arthritis Rheum. 2004 Nov;50(11):3690-7. doi: 10.1002/art.20591.


Objective: To evaluate the effects of the antiresorptive agent alendronate at a daily oral dose of 40 mg in patients with posttraumatic complex regional pain syndrome type I (CRPS I) of the lower extremity.

Methods: Forty patients were enrolled in this 8-week randomized, double-blind, placebo-controlled study of alendronate therapy for CRPS I, a condition associated with regional osteoclastic overactivity. An optional 8-week open extension of alendronate therapy (weeks 12-20) was available after a 4-week period without therapy. Clinical assessments included joint mobility, edema of the lower extremity, tolerance to pressure in the lower extremity, and levels of spontaneous pain. Urinary levels of type I collagen N-telopeptide (NTX) were assessed by enzyme-linked immunosorbent assay. Patients were examined at weeks 4, 8, 12, 16, 20, and 24. Statistical analysis included two-way factorial analysis of variance.

Results: In contrast to placebo-treated patients (n = 20), all of the alendronate-treated patients (n = 19) exhibited a marked and sustained improvement in levels of spontaneous pain, pressure tolerance, and joint mobility, as well as a significant reduction in urinary levels of NTX at weeks 4 and 8. The improvement was maintained at week 12. Twelve patients from each treatment group volunteered for the 8-week open trial, and all of them had a positive response to alendronate.

Conclusion: Our findings support the use of oral alendronate in posttraumatic CRPS I. By reducing local acceleration of bone remodeling, alendronate might relieve pain by effects on nociceptive primary afferents in bone, pain-associated changes in the spinal cord, and possibly also through a central mechanism.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adult
  • Alendronate / administration & dosage
  • Alendronate / adverse effects
  • Alendronate / therapeutic use*
  • Collagen / urine
  • Collagen Type I
  • Double-Blind Method
  • Drug Administration Schedule
  • Female
  • Humans
  • Joints / physiopathology
  • Male
  • Middle Aged
  • Movement
  • Pain / physiopathology
  • Palliative Care
  • Peptides / urine
  • Reflex Sympathetic Dystrophy / drug therapy*
  • Reflex Sympathetic Dystrophy / physiopathology
  • Treatment Outcome


  • Collagen Type I
  • Peptides
  • collagen type I trimeric cross-linked peptide
  • Collagen
  • Alendronate