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Randomized Controlled Trial
. 2010 Nov;95(11):5056-62.
doi: 10.1210/jc.2010-0720. Epub 2010 Jul 14.

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

Matthew T Drake  1 , Bhuma Srinivasan, Ulrike I Mödder, James M Peterson, Louise K McCready, B Lawrence Riggs, Denise Dwyer, Marina Stolina, Paul Kostenuik, Sundeep Khosla
Affiliations
Randomized Controlled Trial

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

Matthew T Drake et al. J Clin Endocrinol Metab. 2010 Nov.

Abstract

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.

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Figures

Figure 1
Figure 1
A, Baseline (BSL) and end point (EP) serum sclerostin levels in the control and PTH-treated women. ***, P < 0.0001 compared with baseline. B, Percent change from baseline in circulating serum sclerostin levels in the control (−4.7 ± 2.6%) and PTH-treated (−12.7 ± 1.9%) women. *, P = 0.017 for comparison with the change in control women.
Figure 2
Figure 2
Plot showing the correlation between bone marrow plasma and peripheral serum sclerostin levels in the control and PTH subjects combined.
See this image and copyright information in PMC

References

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