Effects of parathyroid hormone treatment on circulating sclerostin levels in postmenopausal women.

CONTEXT

Intermittent PTH treatment stimulates bone formation, but the mechanism(s) of this effect remain unclear. Sclerostin is an inhibitor of Wnt signaling, and animal studies have demonstrated that PTH suppresses sclerostin production.

OBJECTIVE

The objective of the study was to test whether intermittent PTH treatment of postmenopausal women alters circulating sclerostin levels.

DESIGN

Prospective study.

SETTING

The study was conducted at a clinical research unit.

PARTICIPANTS AND INTERVENTIONS

Participants included 27 postmenopausal women treated with PTH (1-34) for 14 d and 28 control women.

MAIN OUTCOME MEASURES

Serum sclerostin levels were measured.

RESULTS

Circulating sclerostin levels decreased significantly in the PTH-treated subjects, from (mean ± SEM) 551 ± 32 to 482 ± 31 pg/ml (-12.7%, P < 0.0001) but did not change in the control women (baseline, 559 ± 34 pg/ml; end point, 537 ± 40 pg/ml, P = 0.207; P = 0.017 for difference in changes between groups). Bone marrow plasma was obtained in a subset of the control and PTH-treated subjects (n = 19 each) at the end of the treatment period, and marrow plasma and peripheral serum sclerostin levels were significantly correlated (R = 0.64, P < 0.0001). Marrow plasma sclerostin levels were 24% lower in PTH-treated compared with control women, but perhaps due to the smaller sample size, this difference was not statistically significant (P = 0.173).

CONCLUSIONS

Circulating sclerostin levels correlate with bone marrow plasma levels and are reduced by intermittent PTH therapy in postmenopausal women. Further studies are needed to assess the extent to which decreases in sclerostin production contribute to the anabolic skeletal response to PTH.