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Letters to the Editor |
Penn State University College of Medicine/, Hershey Medical Center, Hershey, PA 17033
Amgen, Inc., Thousand Oaks, CA
1. We agree that differences in serum and plasma OPG1 levels values reported in the literature are frustrating, but these differences should not influence intra-study findings.
2. The rationale for therapeutic use of OPG is not as a replacement paradigm, i.e., to increase serum/marrow levels to normal, but to use pharmacological doses of OPG or a construct to reduce osteoclastic bone resorption. Also, serum/plasma OPG levels may not be a good predictor of local levels (a point we have made before), especially because it has a heparin-binding domain, which suggests that most of it remains within the local microenvironment.
3. Preanalytical issues:
(a) Plasma collection: For the matched serum/plasma values in our report, the plasma anticoagulant was EDTA (K3, 15%) or citrate (3.8% solution of sodium citrate); no heparin was used.
(b) Serum OPG temperature stability: All of the sera/plasma in our study were centrifuged within 2 h of blood drawing for the patient or control subject, and most were centrifuged within 1 h of collection. In addition, the anticoagulated blood plasma was kept at 4°C immediately after collection and during centrifugation, and then stored at -70°C. Therefore, all our serum/plasma were processed and frozen well before the 300-min time frame described by Dovio et al. as producing a 16.7% significant increase in serum OPG levels.
In addition, the data provided by Dovio et al. on refrigeration versus room temperature suggest that OPG degradation may occur and that their assay detects OPG fragments in addition to intact OPG.
4. We agree that it would be helpful to standardize the assays, but differences in assays will probably always exist (as for assays of other molecules).
FOOTNOTES
The abbreviation used is: OPG, osteoprotegerin. ![]()
Received 10/10/02; accepted 10/16/02.
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