Serum Dickkopf-1 is increased and correlates with reduced bone mineral density in patients with thalassemia-induced osteoporosis. Reduction post-zoledronic acid administration

Abstract

Dickkopf-1 is an inhibitor of Wnt signaling, which is crucial for osteoblast differentiation. We evaluated serum levels of Dickkopf-1 in 66 patients with thalassemia-induced osteoporosis who received therapy with zoledronic acid in a placebo-controlled, randomized trial. At baseline, thalassemia patients had increased serum levels of Dickkopf-1 that correlated with reduced bone mineral density of the lumbar spine and the distal radius. High Dickkopf-1 also correlated with increased bone resorption and reduced bone formation markers. Zoledronic acid produced a reduction in serum Dickkopf-1, which was associated with bone mineral density increase after 12 months of therapy. On the contrary, placebo group showed a borderline increase of Dickkopf-1, which was higher in patients who showed deterioration in pain scores. These results suggest that Dickkopf-1 is implicated in the pathogenesis of osteoporosis in thalassemia and reveal Dickkopf-1 as a possible target for the development of novel agents for the management of thalassemia-induced osteoporosis.

Trial registration: ClinicalTrials.gov NCT00346242.

Figures

Figure 1.

Patients with thalassemia and osteoporosis have increased levels of serum Dkk1 compared with normal controls (A). Increased Dkk1 levels correlated with reduced BMD of the lumbar spine (B) and the wrist (C) but also with reduced bALP (bone formation marker) (D).

Figure 2.

Zoledronic acid administration produced a reduction in Dkk1 serum levels but in placebo group a borderline increase of Dkk1 was observed.