title: Sclerostin and DKK1 in primary hyperparathyroidism.
abstract: Bone formation is influenced by the Wnt pathway through effects on osteoblast functionality, and these actions are opposed by two antagonists: sclerostin and Dickkopf-1 (DKK1). Decreased levels of serum sclerostin were found after treatment with the PTH analogue teriparatide and in patients with primary hyperparathyroidism (PHPT), while treatment with teriparatide of postmenopausal osteoporosis is associated with increases in serum DKK1. We studied mineral metabolism and Wnt pathway in 21 postmenopausal women affected by PHPT and in 42 age-matched healthy women. Mean serum calcium and PTH were significantly higher and serum phosphates significantly lower in the PHPT group compared with the control group. Serum 25-OH-vitamin D (25OHD) was lower in PHPT patients and 1,25 dihydroxy-vitamin D [1,25(OH)2D] was significantly higher. Patients with PHPT had significantly higher levels of bone alkaline phosphatase (BAP) and of serum C-terminal telopeptides of type I collagene (sCTX). Serum sclerostin in PHPT was significantly lower (-26 %) and serum DKK1 significantly higher (+57 %) than in healthy control subjects. Serum PTH was positively correlated with 1,25OH2D (p < 0.001), BAP (p = 0.036), sCTX (p = 0.003), and DKK1 (p = 0.007) and negatively with 25OHD (p = 0.002) and sclerostin (p = 0.02). In PHPT patients, serum sclerostin was negatively correlated with BAP (p = 0.038) and sCTX (p = 0.07). Patients with PHPT have significantly lower sclerostin and higher DKK1 levels compared with healthy postmenopausal control subjects. Further studies are warranted in order to verify whether the balance between these two opposite effects on Wnt function might help explain the variable bone involvement among patients with PHPT.
authors: Unit of Rheumatology, University of Verona, P.le Scuro 10, 37134, Verona, Italy. ombretta.viapiana@univr.it
authors: Ombretta
authors: O
authors: Viapiana
authors: Elena
authors: E
authors: Fracassi
authors: Sonila
authors: S
authors: Troplini
authors: Luca
authors: L
authors: Idolazzi
authors: Maurizio
authors: M
authors: Rossini
authors: Silvano
authors: S
authors: Adami
authors: Davide
authors: D
authors: Gatti
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000368:Aged; D000369:Aged, 80 and over; D000469:Alkaline Phosphatase / Q000097:blood; D015415:Biomarkers / Q000097:blood; D019485:Bone Morphogenetic Proteins / Q000097:blood*; D002118:Calcium / Q000097:blood; D016022:Case-Control Studies; D024042:Collagen Type I / Q000097:blood; D005260:Female; D005819:Genetic Markers; D006801:Humans; D049950:Hyperparathyroidism, Primary / Q000097:blood*; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood*; D008875:Middle Aged; D010281:Parathyroid Hormone / Q000097:blood; D010455:Peptides / Q000097:blood; D015398:Signal Transduction / Q000502:physiology*; D051153:Wnt Proteins / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D015415:Biomarkers; D019485:Bone Morphogenetic Proteins; D024042:Collagen Type I; C501126:DKK1 protein, human; D005819:Genetic Markers; D036341:Intercellular Signaling Peptides and Proteins; D010281:Parathyroid Hormone; D010455:Peptides; C422903:SOST protein, human; D051153:Wnt Proteins; C052929:collagen type I trimeric cross-linked peptide; D000469:Alkaline Phosphatase; D002118:Calcium