Short-term high-dose, but not low-dose, corticosteroid treatment reduces serum sclerostin levels.

Renate T de Jongh¹, Daniel van Raalte¹, Martin den Heijer¹.

¹Department of Internal Medicine and Endocrinology, AUMC, Amsterdam.

Background A central feature in glucocorticosteroid-induced osteoporosis is reduced bone formation. Wnt signaling is important for osteoblast proliferation and differentiation and thus bone formation. Glucocorticosteroids depress osteoblast function through inhibition of Wnt  signaling in vitro and increase levels of Wnt signaling inhibitors such as sclerostin in animal studies.  Data on effects of glucocorticoid treatment on circulating sclerostin levels in humans are scarce and contradictory. A randomized trial has not been performed.

Objective To examine effects of short-term low- and high-dose glucocorticoid treatment on circulating sclerostin levels in healthy individuals.

Methods In a randomised, placebo-controlled, dose-response intervention study, 48 healthy normoglycaemic men were allocated to receive prednisolone 30 mg once daily (n = 18), prednisolone 7.5 mg once daily (n = 16) or placebo (n =14 ) for 2 weeks using block randomisation. Before and after the intervention serum sclerostin was measured using the MesoScale Discovery chemiluminescence assay and serum P1NP using the Orion Diagnostica radioimmunoassay.

Results Baseline characteristics did not differ between intervention groups (mean±SD, age: 21±2 years; BMI: 21.9±1.8 kg/m2; median[interquartile range]: sclerostin 110 [88 to 123] pg/ml; P1NP 73.0 [57.3 to 103.0] µg/l). Compared to placebo, prednisolone 30 mg decreased sclerostin levels (-11 [-39 to -1] vs. 2 [-7 to 18] pg/ml , p=0.013) and P1NP levels (-28.5 [-37.8 to -19.8] vs. 1.5 [-18.5 to 14.0] µg/l, p<0.001). Prednison 7.5 mg did not alter sclerostin (-9 [-26 to 15] vs. 2 [-7 to 18] pg/ml , p=0.208) but tended to decrease P1NP levels (-7.5 [-27.3 to -2.3] vs. 1.5 [-18.5 to 14.0] µg/l, p=0.095).

Conclusions Short-term high-dose, but not low-dose, prednisone treatment reduces sclerostin levels in healthy young individuals. Whether this reflects a reduction in number of functional osteocytes or a counterregulatory mechanism for impaired osteoblast function remains to be elucidated.