Osteoprotegerin: a new biomarker for impaired bone metabolism in complex regional pain syndrome?

Pain. 2014 May;155(5):889-895. doi: 10.1016/j.pain.2014.01.014. Epub 2014 Jan 18.


Osteoprotegerin (OPG) is important for bone remodeling and may contribute to complex regional pain syndrome (CRPS) pathophysiology. We aimed to assess the value of OPG as a biomarker for CRPS and a possible correlation with radiotracer uptake in 3-phase bone scintigraphy (TPBS). OPG levels were analyzed in 23 CRPS patients (17 women; mean age 50±9.0 years; disease duration: 12 weeks [IQR 8-24]), 10 controls (6 women; mean age 58±9.6 years) and 21 patients after uncomplicated fractures (12 women; mean age: 43±15 years; time after fracture: 15 weeks [IQR: 6-22]). The CRPS and control patients also underwent TPBS. OPG in CRPS patients was significantly increased by comparison with both control groups (P=0.001; Kruskal-Wallis test; CRPS patients: 74.1 pg/mL [IQR: 47.1-100.7]; controls: 46.7 pg/mL [IQR: 35.5-55.0]; P=0.004; fracture patients: 45.9 pg/mL [IQR: 37.5-56.7]; P=0.001). As a diagnostic test for CRPS, OPG had a sensitivity of 0.74, specificity of 0.80, positive predictive value of 68% and negative predictive value of 84%. Receiver operating characteristic curve analysis showed an area under the curve of 0.80 (CI: 0.68-0.91). For the CRPS-affected hand, a significant correlation between OPG and TPBS region of interest analysis in phase III was detected (carpal bones; r=0.391; P=0.03). The persistent OPG increase in CRPS indicates enhanced osteoblastic activity shown by increased radiotracer uptake in TPBS phase III. A contribution of bone turnover to CRPS pathophysiology is likely. OPG might be useful as a biomarker for CRPS.

Keywords: Biomarker; CRPS; Osteoprotegerin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Biomarkers / blood
  • Bone Diseases, Metabolic / blood
  • Bone Diseases, Metabolic / diagnosis*
  • Bone Diseases, Metabolic / etiology
  • Complex Regional Pain Syndromes / blood
  • Complex Regional Pain Syndromes / complications*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Osteoprotegerin / blood*
  • Sensitivity and Specificity


  • Biomarkers
  • Osteoprotegerin