title: Effect of recent spinal cord injury on wnt signaling antagonists (sclerostin and dkk-1) and their relationship with bone loss. A 12-month prospective study.
abstract: Spinal cord injury (SCI) has been associated with a marked increase in bone loss and bone remodeling, especially short-term after injury. The absence of mechanical load, mediated by osteocyte mechanosensory function, seems to be a causative factor related to bone loss in this condition. However, the pathogenesis and clinical management of this process remain unclear. Therefore, the aim of the study was to analyze the effect of recent SCI on the Wnt pathway antagonists, sclerostin and Dickkopf (Dkk-1), and their relationship with bone turnover and bone mineral density (BMD) evolution. Forty-two patients (aged 35 ± 14yrs) with a recent (<6months) complete SCI were prospectively included. Sclerostin and Dkk-1, bone turnover markers (bone formation: PINP, bone ALP; resorption: sCTx) and BMD (lumbar spine, proximal femur, total body and lower extremities [DXA]) were assessed at baseline and at 6 and 12 months. The results were compared with a healthy control group. 22/42 patients completed the 12-month follow-up. At baseline, SCI patients showed a marked increase in bone markers (PINP and sCTx), remaining significantly increased at up to 6 months of follow-up. Additionally, they presented significantly increased Dkk-1 values throughout the study, whereas sclerostin values did not significantly change. BMD markedly decreased at the proximal femur (-20.2 ± 5.4%, p < 0.01), total body (-5.7 ± 2.2%, p = 0.02) and lower extremities (-13.1 ± 4.5%, p = 0.01) at 12 months. Consequently, 59% of patients developed densitometric osteoporosis at 12 months. Patients with higher Dkk-1 values (>58 pmol/L) at baseline showed higher sublesional BMD loss. In conclusion, this study shows that short-term after SCI there is a marked increase in bone turnover and bone loss, the latter associated with an increase in Dkk-1 serum levels. The persistence of increased levels of this Wnt antagonist throughout the study and their relationship with the magnitude of bone loss suggests a contributory role of this mediator in this process.
authors.affiliation: Rheumatology Department, Hospital Clinic of Barcelona, Barcelona, Spain.
authors.forename: Laia
authors.initials: L
authors.lastname: Gifre
authors.affiliation: Guttmann Neurorehabilitation Institute, Universitat Autònoma de Barcelona, Badalona, Spain.
authors.forename: Joan
authors.initials: J
authors.lastname: Vidal
authors.affiliation: Public Health Department, University of Barcelona, Barcelona, Spain.
authors.forename: Josep L
authors.initials: JL
authors.lastname: Carrasco
authors.affiliation: Department of Biochemistry and Molecular Genetics, Hospital Clinic of Barcelona, Barcelona, Spain.
authors.forename: Xavier
authors.initials: X
authors.lastname: Filella
authors.affiliation: CIBERehd, Barcelona, Spain.
authors.forename: Silvia
authors.initials: S
authors.lastname: Ruiz-Gaspà
authors.affiliation: Nuclear Medicine Department, Hospital Clínic of Barcelona, Barcelona, Spain.
authors.forename: Africa
authors.initials: A
authors.lastname: Muxi
authors.affiliation: Guttmann Neurorehabilitation Institute, Universitat Autònoma de Barcelona, Badalona, Spain.
authors.forename: Enric
authors.initials: E
authors.lastname: Portell
authors.affiliation: Rheumatology Department, Hospital Clinic of Barcelona, Barcelona, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Monegal
authors.affiliation: Rheumatology Department, Hospital Clinic of Barcelona, Barcelona, Spain.|CIBERehd, Barcelona, Spain.
authors.forename: Nuria
authors.initials: N
authors.lastname: Guañabens
authors.affiliation: Rheumatology Department, Hospital Clinic of Barcelona, Barcelona, Spain.|CIBERehd, Barcelona, Spain.
authors.forename: Pilar
authors.initials: P
authors.lastname: Peris
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000293:Adolescent; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D019485:Bone Morphogenetic Proteins / Q000097:blood*; D001862:Bone Resorption / Q000097:blood* / Q000209:etiology; D005260:Female; D005500:Follow-Up Studies; D005819:Genetic Markers; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D013119:Spinal Cord Injuries / Q000097:blood* / Q000150:complications; D060449:Wnt Signaling Pathway
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D015415:Biomarkers; D019485:Bone Morphogenetic Proteins; C501126:DKK1 protein, human; D005819:Genetic Markers; D036341:Intercellular Signaling Peptides and Proteins; C422903:SOST protein, human
keywords: DKK-1; OSTEOPOROSIS; SCLEROSTIN; SPINAL CORD INJURY; WNT SIGNALING