Increased circulating Dickkopf-1 in Paget's disease of bone.
Dickkopf-1 (Dkk-1) 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.


OBJECTIVE
To see if increased Dkk-1 was detected in serum from patients with PDB.


RESULTS
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.


CONCLUSIONS
Dkk-1 may be a useful biomarker of PDB and we speculate that Dkk-1 may play a central role in the etiology of PDB.
Marshall
Michael J
MJ
Charles Salt Centre for Human Metabolism, Robert Jones and Agnes Hunt Orthopaedic Hospital NHS Trust, Oswestry, Shropshire, SY10 7AG, UK. michael.marshall@rjah.nhs.uk
Evans
Sally F
SF
Sharp
Christopher A
CA
Powell
Diane E
DE
McCarthy
Helen S
HS
Davie
Michael W J
MW
D000368:Aged; D000369:Aged, 80 and over; D000469:Alkaline Phosphatase / Q000097:blood; D016022:Case-Control Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood*; D008297:Male; D008875:Middle Aged; D010001:Osteitis Deformans / Q000097:blood* / Q000201:enzymology
C501126:DKK1 protein, human; D036341:Intercellular Signaling Peptides and Proteins; D000469:Alkaline Phosphatase