title: Distinct effect of zoledronate and clodronate on circulating levels of DKK1 and sclerostin in women with postmenopausal osteoporosis.
abstract: The coupling of bone formation to bone resorption during treatment of postmenopausal osteoporosis with antiresorbers might be related to changes in Wnt/b-catenin signaling. We compared the effects of two bisphosphonate treatments on two Wnt-inhibitors Sclerostin (SOST) and Dickkopf-related protein 1 (DKK1). The study population included 74 women with postmenopausal osteoporosis participating simultaneously in two multicenter, placebo controlled trials. The patients were randomized to: intramuscular clodronate 100mg/week (CLO) (N=36), and yearly intravenous therapy with 5mg zoledronate (ZOL) (N=18) and placebo (N=20). Bone turnover markers (intact N-propeptide of type I collagen [P1NP], C-terminal telopeptide of type I collagen [CTX]) remained unchanged in the placebo group while they significantly decreased during treatment with the two bisphosphonates, versus both placebo and baseline. In CLO treated patients serum DKK1 remained stable over the entire period of observation while serum SOST levels increased significantly after 12months of treatment both versus placebo group (p<0,005), baseline (p<0,001) and ZOL treated group. In the ZOL group, DKK1 levels increased significantly within one month and for the following 6months and it fell back to baseline values at 12months. The second ZOL infusion was again associated with an increase in DKK1 a month later, although to a lesser extent. In conclusion, in this study we have found that the treatment of postmenopausal osteoporosis with intermittent yearly ZOL is associated with transient and declining increases in DKK1 while continuous treatment with CLO, results in a late increase in serum SOST. These preliminary results and further ad hoc studies might contribute to shed light on our understanding of the bone coupling effects taking place during treatment of osteoporosis with different anti-resorbers or with different treatment regimens.
authors.affiliation: Unit of Rheumatology, Department of Medicine, University of Verona, P.le L. Scuro n 2, 37134 Verona, Italy. Electronic address: davide.gatti@univr.it.
authors.forename: Davide
authors.initials: D
authors.lastname: Gatti
authors.affiliation: Unit of Rheumatology, Department of Medicine, University of Verona, P.le L. Scuro n 2, 37134 Verona, Italy. Electronic address: ombretta.viapiana@univr.it.
authors.forename: Ombretta
authors.initials: O
authors.lastname: Viapiana
authors.affiliation: Unit of Rheumatology, Department of Medicine, University of Verona, P.le L. Scuro n 2, 37134 Verona, Italy. Electronic address: luca.idolazzi@univr.it.
authors.forename: Luca
authors.initials: L
authors.lastname: Idolazzi
authors.affiliation: Unit of Rheumatology, Department of Medicine, University of Verona, P.le L. Scuro n 2, 37134 Verona, Italy. Electronic address: elena.fracassi@univr.it.
authors.forename: Elena
authors.initials: E
authors.lastname: Fracassi
authors.affiliation: Unit of Rheumatology, Department of Medicine, University of Verona, P.le L. Scuro n 2, 37134 Verona, Italy. Electronic address: johnny.yc2006@gmail.com.
authors.forename: Claudio
authors.initials: C
authors.lastname: Ionescu
authors.affiliation: Unit of Rheumatology, Department of Medicine, University of Verona, P.le L. Scuro n 2, 37134 Verona, Italy. Electronic address: carmen_dartizio@libero.it.
authors.forename: Carmela
authors.initials: C
authors.lastname: Dartizio
authors.affiliation: Unit of Rheumatology, Department of Medicine, University of Verona, P.le L. Scuro n 2, 37134 Verona, Italy. Electronic address: sonila.troplini@yahoo.it.
authors.forename: Sonila
authors.initials: S
authors.lastname: Troplini
authors.affiliation: Unit of Rheumatology, Department of Medicine, University of Verona, P.le L. Scuro n 2, 37134 Verona, Italy. Electronic address: vid1488@gmail.com.
authors.forename: Vidya
authors.initials: V
authors.lastname: Kunnathully
authors.affiliation: Unit of Rheumatology, Department of Medicine, University of Verona, P.le L. Scuro n 2, 37134 Verona, Italy. Electronic address: silvano.adami@univr.it.
authors.forename: Silvano
authors.initials: S
authors.lastname: Adami
authors.affiliation: Unit of Rheumatology, Department of Medicine, University of Verona, P.le L. Scuro n 2, 37134 Verona, Italy. Electronic address: maurizio.rossini@univr.it.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Rossini
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000368:Aged; D050071:Bone Density Conservation Agents / Q000627:therapeutic use*; D019485:Bone Morphogenetic Proteins / Q000097:blood*; D004002:Clodronic Acid / Q000627:therapeutic use*; D004164:Diphosphonates / Q000627:therapeutic use*; D005260:Female; D005819:Genetic Markers; D006801:Humans; D007093:Imidazoles / Q000627:therapeutic use*; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood*; D008875:Middle Aged; D015663:Osteoporosis, Postmenopausal / Q000097:blood* / Q000188:drug therapy*; D000077211:Zoledronic Acid
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D050071:Bone Density Conservation Agents; D019485:Bone Morphogenetic Proteins; C501126:DKK1 protein, human; D004164:Diphosphonates; D005819:Genetic Markers; D007093:Imidazoles; D036341:Intercellular Signaling Peptides and Proteins; C422903:SOST protein, human; D004002:Clodronic Acid; D000077211:Zoledronic Acid
keywords: Clodronate; DKK-1; Sclerostin; Zoledronate