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. DESIGN: 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. CONCLUSION: 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.
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. DESIGN: 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. CONCLUSION: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.
Authors: Xiaolin Tu; Yumie Rhee; Keith W Condon; Nicoletta Bivi; Matthew R Allen; Denise Dwyer; Marina Stolina; Charles H Turner; Alexander G Robling; Lilian I Plotkin; Teresita Bellido Journal: Bone Date: 2011-10-30 Impact factor: 4.398
Authors: Alexander T Faje; Pouneh K Fazeli; Debra K Katzman; Karen K Miller; Anne Breggia; Clifford J Rosen; Nara Mendes; Anne Klibanski; Madhusmita Misra Journal: Bone Date: 2012-06-15 Impact factor: 4.398
Authors: Elizabeth Grethen; Kathleen M Hill; RoseMarie Jones; Brenda M Cacucci; Christine E Gupta; Anthony Acton; Robert V Considine; Munro Peacock Journal: J Clin Endocrinol Metab Date: 2012-02-22 Impact factor: 5.958
Authors: Matthew T Drake; Jennifer S Fenske; Frank A Blocki; Claudia Zierold; Natasha Appelman-Dijkstra; Socrates Papapoulos; Sundeep Khosla Journal: Bone Date: 2018-03-14 Impact factor: 4.398