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

Abstract

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.

Influence of Parathyroidectomy on Bone Metabolism and Bone Pain in Patients with Secondary Hyperparathyroidism

“…The best laboratory marker for an objective measurement of bone pain seems to be OPG. Similar results for OPG were found in patients complaining about the regional pain syndrome [66]. …”

Juvenile idiopathic arthritis and rheumatoid arthritis: bacterial diversity in temporomandibular joint synovial fluid in comparison with immunological and clinical findings

“…Osteoprotegerin (OPG) was low in patients reporting most pain in this study, a finding in contrast with previous studies focusing on OPG as a biomarker in pain syndromes (Krämer et al 2014). Low OPG may be induced by a local factor, such as PTH, IL-6-feedback, or other regulatory mechanisms, but may be induced by methotrexate as well, although the data are few and inconclusive.…”

“…This is highly interesting, TNF-α being a target in general medication in both JIA and RA, and OPG, believed to be a biomarker in pain syndromes (Krämer et al 2014). …”

Neurogenic neuroinflammation in fibromyalgia and complex regional pain syndrome

“…Levels of osteoprotegerin (OPG) are also elevated in the early phase of CRPS, indicative of acute effects on bone remodelling. 66 The common and prominent CRPS features of bone marrow oedema and osteopenia are also probably related to neurogenic inflammation, through secretion of neuropeptides such as OPG. Additionally, late clinical features, such as visceral pain, rashes, skin ulceration and fibrosis of palmar aponeuroses and joint capsules might also relate to persistent neurogenic inflammation in CRPS.…”