Patients with primary hyperparathyroidism have lower circulating sclerostin levels than euparathyroid controls.
OBJECTIVE
In vitro and in vivo studies in animal models have shown that parathyroid hormone (PTH) inhibits the expression of the SOST gene, which encodes sclerostin, an osteocyte-derived negative regulator of bone formation. We tested the hypothesis that chronic PTH excess decreases circulating sclerostin in humans.


METHODS
We studied 25 patients with elevated serum PTH concentrations due to primary hyperparathyroidism (PHPT) and 49 patients cured from PHPT after successful parathyroidectomy (PTx; euparathyroid controls (EuPTH)).


METHODS
We measured plasma PTH and serum sclerostin levels and the serum markers of bone turnover alkaline phosphatase, P1NP, and β-CTX.


RESULTS
As expected by the design of the study, mean plasma PTH was significantly higher (P<0.001) in PHPT patients (15.3 pmol/l; 95% confidence interval (CI): 11.1-19.5) compared with that of EuPTH controls (4.1 pmol/l; 95% CI: 3.6-4.5). PHPT patients had significantly lower serum sclerostin values compared with those in EuPTH subjects (30.5 pg/ml; 95% CI: 26.0-35.1 vs 45.4 pg/ml; 95% CI: 40.5-50.2; P<0.001) and healthy controls (40.0 pg/ml; 95% CI: 37.1-42.9; P=0.01). Plasma PTH concentrations were negatively correlated with serum sclerostin values (r=-0.44; P<0.001). Bone turnover markers were significantly correlated with PTH, but not with sclerostin.


CONCLUSIONS
Patients with PHPT have significantly lower serum sclerostin values compared with PTx controls with normal PTH concentrations. The negative correlation between PTH and sclerostin suggests that SOST is downregulated by PTH in humans.
van Lierop
A H
AH
Department of Endocrinology and Metabolic Diseases, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands.
Witteveen
J E
JE
Hamdy
N A T
NA
Papapoulos
S E
SE
D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D019485:Bone Morphogenetic Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000097:blood*; D016723:Bone Remodeling / Q000502:physiology; D015536:Down-Regulation / Q000502:physiology; D005260:Female; D005819:Genetic Markers; D006801:Humans; D049950:Hyperparathyroidism, Primary / Q000097:blood* / Q000175:diagnosis; D008297:Male; D008875:Middle Aged; D010280:Parathyroid Glands / Q000378:metabolism*; D010281:Parathyroid Hormone / Q000097:blood* / Q000502:physiology
D048868:Adaptor Proteins, Signal Transducing; D015415:Biomarkers; D019485:Bone Morphogenetic Proteins; D005819:Genetic Markers; D010281:Parathyroid Hormone; C422903:SOST protein, human