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Technical Briefs |
Service d'Explorations Fonctionnelles, Hôpital Necker-Enfants Malades, 149 rue de Sèvres, 75015, Paris, France
a author for correspondence: fax 33/1 40 61 55 87
Osteocalcin (Oc) is a 49-amino-acid noncollagenous protein
synthesized by osteoblasts. Because of the presence of three
-carboxyglutamic acid (GLA) residues, newly synthesized Oc will be
primarily bound to hydroxyapatite present in bone matrix, only a small
fraction being released into the circulation (1). Although
serum Oc concentration is considered a valid marker of bone turnover in
most situations (2), it reflects specifically bone
formation when resorption and formation are uncoupled as observed in
corticoid-induced osteoporosis (3). Several reports have
stressed recently that absolute Oc concentrations obtained with various
in-house (4) or commercial (5) assays cannot
be compared directly. An important cause for the discrepancies between
Oc assays is the variabily of the anti-Oc antibody specificity for the
circulating Oc fragments described by Garnero et al. (6).
The intact Oc molecule (149 Oc) is highly susceptible to tryptic
proteolysis because of the presence of 2 Arg-Arg sites in positions
1920 and 4344 (7). When serum samples are not rapidly
frozen, 149 Oc will be degraded quickly, the largest degradation
product being a big N-terminal mid-fragment (143 Oc). This fragment
is accumulated in patients with chronic renal failure (CRF)
(6). This problem of degradation is a major drawback in
terms of specificity with an Oc assay that recognizes only 149 Oc. On
the contrary, an Oc assay recognizing both 149 Oc and 143 Oc with
equal affinity will be less sensitive to the effect of proteolysis
(8) but of very limited value in CRF patients, as even
those with adynamic bone disease will appear to have high serum Oc
concentrations (9). Antibody specificity is thus an
important variable to be taken into account when interpreting serum Oc
concentrations obtained
Acknowledgments
References
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