• Dickkopf-1 as a potential therapeutic target in Paget's disease of bone

      McCarthy, Helen S.; Marshall, Michael J.; Charles Salt Centre, Robert Jones and Agnes Hunt Orthopaedic Hospital NHS Trust in Oswestry / University of Chester ; Charles Salt Centre, Robert Jones and Agnes Hunt Orthopaedic Hospital NHS Trust in Oswestry (Ashley, 2010-01-08)
      This article discusses Dickkopf-1 (DKK-1), which is a soluble inhibitor of Wnt signalling and its excessive expression contributes to bone loss in rheumatoid arthritis and multiple myeloma. New therapeutics have been developed for treatment of these conditions that target DKK-1 expression. DKK-1 is elevated in serum of patients with Paget's disease of the bone (PDB) and evidence is accumulating for a role of DKK-1 in PDB. At present there is no cure for PDB and the current treatment of choice are bisphosphonates. These treat the resorptive phase of PDB but do not prevent its return. This article offers a new perspective on the aetiology of PDB and speculate on DKK-1 as a therapeutic target.
    • Increased circulating Dickkopf-1 in Paget's disease of bone

      Marshall, Michael J.; Evans, Sally F.; Sharp, Christopher A.; Powell, Diane E.; McCarthy, Helen S.; Davie, Michael W. J.; Charles Salt Centre, Robert Jones and Agnes Hunt Orthopaedic Hospital NHS Trust in Oswestry / University of Chester ; Charles Salt Centre, Robert Jones and Agnes Hunt Orthopaedic Hospital NHS Trust in Oswestry (Elsevier, 2009-07)
      This article discusses Dickkopf-1 (Dkk-1), which is a secreted inhibitor of Wnt signaling which in adults regulates bone turnover. Dkk-1 over-production is implicated in osteolytic disease where it inhibits bone formation and stimulates bone breakdown. Recently it was reported that osteoblastic cells from Paget's disease of bone (PDB) over-expressed Dkk-1. This study aimed yo see if increased Dkk-1 was detected in serum from patients with PDB. The results showed that Dkk-1 and total serum alkaline phosphatase activity (tsAP) were significantly elevated in sera from PDB patients. Patients with polyostotic PDB had significantly higher levels of tsAP but not Dkk-1, than monostotic patients. TsAP but not Dkk-1, was significantly lower in sera from bisphosphonate treated versus untreated PDB patients. Dkk-1 and tsAP were not significantly correlated. Dkk-1 may be a useful biomarker of PDB and the authors speculate that Dkk-1 may play a central role in the etiology of PDB.