Higher Level of Dickkopf-1 is Associated with Low Bone Mineral Density and Higher Prevalence of Vertebral Fractures in Patients with Ankylosing Spondylitis

Abstract

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.

Correlation of dickkopf-1 concentrations in plasma and synovial fluid to the severity of radiographic signs of equine osteoarthritis

“…Worsening osteoarthritis in low motion joints is often characterized by minimal evidence of synovitis, subchondral bone lysis, and a progression towards ankylosis (1). Previous studies have documented a direct correlation between bone erosion, osteopenia, and the overexpression of Dkk-1 (6,10,16). We anticipated that a similar relationship might exist in the horse, however no significant association was established when comparing subchondral bone lysis scores and Dkk-1 values.…”

“…In the horse, preliminary work has been done to characterize the Wnt-signalling molecules involved in the regulatory pathways of equine chondrocytes during development (15). More recently, Dkk-1 was found to be overexpressed in the early stages of equine osteochondrosis (16). The antagonism of the Wnt signalling pathway produced by Dkk-1 has been shown to be beneficial in rats with knee osteoarthritis by reducing cartilage fibrillation, subchondral bone damage, and serum degradation biomarkers (17).…”

Femur Bone Mineral Density and Pentosidine Level Distinguish Ankylosing Spinal Disorder Patients with and without Sacroiliac Ankylosis

“…Young patients with AS have low levels of active vitamin D3 and sclerostin (secreted from bone tissues and inhibits Wnt, a signaling factor necessary for bone formation by osteoblasts) and high dickkopf-1 levels [23][24][25][26][27] . Senolt et al reported that the critical bone formation factor, DKK-1, is low in the serum of patients with DISH.…”

Osteoimmunology in rheumatoid and psoriatic arthritis: potential effects of tofacitinib on bone involvement

“…In more detail, preclinical studies have shown that the overexpression of DKK1 causes osteopenia in mice, while reduced DKK1 expression is associated with high bone mass [43,44]. Furthermore, altered serum levels of DKK1, reported in patients with inflammatory rheumatic diseases, including RA and ankylosing spondylitis, suggest the involvement of DKK1 in bone loss in inflammatory arthropathies [45][46][47][48][49].…”