Zusammenfassung
In präklinischen Studien wurde gezeigt, dass Osteoprotegerin (OPG) einen hemmenden Einfluss auf die Osteoklasten ausübt und daher eine wesentliche Rolle im Knochenstoffwechsel spielt. Ziel dieser Studie war es denklinischen Stellenwert von OPG zu evaluieren. Ist auch bei Menschen ein hoher Serum-OPG Spiegel mit niedriger Knochenresorption und konsekutiv höherer Knochendichte verbunden?
Bei 177 gesunden Frauen (17–85 Jahre) und bei 48 unbehandelten Patientinnen (71±5 Jahre) mit primärer postmenopausaler Osteoporose wurde OPG im Serum gemessen und in Relation zu Alter, Knochendichte, Knochenstoffwechselparametern un — im Fall der Patientinnen mit Osteoporose — zu prävalenten Wirbelkörperfrakturen gestellt.
Bei den gesunden Probanden korrelierte OPG positiv mit dem Alter (r=0,25, p<0,001), während kein Zusammenhang mit der Knochendichte oder den Knochenumbauparametern gefunden wurde. Bei den Osteoporose-Patientinnen hingegen zeigte sich eine klare Korrelation mit den Knochenmarkern: Serum-Crosslaps r=+0.82, p<0.0001; Osteokalzin r=+0,69; p<0,0001.
Nach Normalisierung der Serum-OPG Werte für die Knochendichte und Umbaumarker zeigten Patientinnen mit prävalenten Wirbelkörperfrakturen deutlich niedrigere Werte im Vergleich zu den Patientinnen ohne Frakturen (57±8 vs. 97±10 pg/ml; p<0,01).
Der altersabhängige Anstieg von OPG als antiresorptiver Faktor könnte einen insuffizienten parakrinen Kompensationsversuch der Osteoblasten auf den Knochenverlust im Alter darstellen. Der klare Zusammenhang von OPG mit den Knochenumbaumarkern bei Patientinnen mit Osteoporose ist wahrscheinlich als Ausdruck einer erhöhten RANKL/OPG Expression zu werten.
Niedrige OPG-Spiegel scheinen mit einem erhöhten Frakturrisiko assoziiert zu sein. Der individuelle Serum OPG Wert könnte unter Berücksichtigung des Knochenstoffwechsels ein prädiktiver Faktor für das Frakturrisiko bei Frauen mit primärer postmenopausaler Osteoporose sein.
Summary
Pre-clinical data have shown that osteoprotegerin (OPG) inhibits osteoclast function and therefore plays an important role in bone remodelling. This study aimed to evaluate theclinical value of serum OPG. Do higher OPG serum levels reflect decreased bone resorption and perhaps higher bone mass in women?
Serum OPG levels were measured in 177 healthy women (aged 17–85 years) and in 48 untreated patients (mean age 71±5) with established osteoporosis, and related to age, bone mass, markers of bone turnover and, in the case of patients with osteoporosis, to pre-existing vertebral fractures.
In healthy women OPG levels showed a positive correlation with age (r=0.25, p<0.001) but not to bone mass or markers of bone turnover. In women with osteoporosis, however, there was a strong relationship between serum OPG and markers of bone turnover (serum c-terminal crosslinked telopeptides of type I collagen (sCTX): r=+0.82, p<0.0001; osteocalcin (OC): r=+0.69, p<0.0001), with patients who had higher levels of bone-turnover markers showing higher serum levels of OPG. After adjustment for bone mass and bone markers, patients with pre-existing vertebral fractures had significantly lower serum OPG levels than patients without fractures (57±8 vs. 97±10 pg/ml, [mean±SE], p<0.01).
The age-dependent increase of OPG as an antiresorptive factor may reflect an insufficient paracrine mechanism of bone cells to compensate for bone loss in older age. In patients with osteoporosis, however, OPG correlated strongly with markers of bone turnover; this may point toward a higher level of RANKL/OPG expression in these patients.
Finally, low OPG serum levels seem to be associated with vertebral fractures. We hypothesise that low OPG levels in preset conditions of bone turnover may indicate a higher risk of fracture in patients with osteoporosis.
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Fahrleitner-Pammer, A., Dobnig, H., Piswanger-Soelkner, C. et al. Osteoprotegerin serum levels in women: Correlation with age, bone mass, bone turnover and fracture status. Wien Klin Wochenschr 115, 291–297 (2003). https://doi.org/10.1007/BF03040334
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DOI: https://doi.org/10.1007/BF03040334