Higher Level of Dickkopf-1 is Associated with Low Bone Mineral Density and Higher Prevalence of Vertebral Fractures in Patients with Ankylosing Spondylitis
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Patients with ankylosing spondylitis (AS) have an increased risk of bone loss and vertebral fractures. In this study, we explored the hypothesis that the excess bone loss and vertebral fractures might be related with the activity of the Wingless signaling pathway, and in particular with the serum levels of its circulating inhibitors, Sclerostin and Dickkopf-1 (DKK1). We recruited 71 patients diagnosed with AS. Lateral radiographs of the total spine were analyzed to detect the presence of vertebral fractures, and bone mineral density (BMD) was assessed in all patients using dual X-ray absorptiometry at lumbar spine and proximal femoral site. Blood samples were obtained and levels of C-reactive protein (CRP), DKK1, and Sclerostin were measured. Blood samples from 71 healthy sex- and age-matched volunteers were collected to be used as controls. Vertebral fractures were detected more commonly among men than in women (29 vs 8 %, respectively). DKK1, but not Sclerostin serum levels, were inversely correlated to lumbar spine Z-score BMD. Patients with one or more prevalent vertebral fractures had significantly higher DKK1 levels, without significant difference in Sclerostin serum levels. A significant positive correlation was found between DKK1 serum levels and CRP (r = 0.240, p = 0.043). The association we found between serum DKK1 levels and BMD values and vertebral fracture prevalence suggests that DKK1 might contribute to the severity of osteoporosis in AS.
KeywordsAnkylosing spondylitis DKK1 Bone mineral density Osteoporosis Sclerostin
The authors would like to thank the laboratory teams, especially Caterina Fraccarollo and Cristina Bosco for performing the biochemical analyses. The authors thank Sara Rossini who provided editorial assistance.
No funding sources to disclose.
Compliance with Ethical Standards
Conflict of Interest
Maurizio Rossini, Ombretta Viapiana, Luca Idolazzi, Francesco Ghellere, Elena Fracassi, Sonila Troplini, Maria Rosaria Povino, Vidya Kunnathully, Silvano Adami, and Davide Gatti declare that they have no conflict of interest.
Human and Animal Rights and Informed Consent
The clinical study was conducted in accordance with the ethics principles of the Declaration of Helsinki and was approved by the local ethics committee. Each enrolled patient signed the informed consent to participate in the study.