Changes in Dkk-1, sclerostin, and RANKL serum levels following discontinuation of long-term denosumab treatment in postmenopausal women

• Published in: Bone (New York, N.Y.) N.Y.), 2019-06, Vol.123, p.191-195
• Main Authors: Fassio, A., Adami, G., Benini, C., Vantaggiato, E., Saag, K.G., Giollo, A., Lippolis, I., Viapiana, O., Idolazzi, L., Orsolini, G., Rossini, M., Gatti, D.
• Format: Article
• Language: English
• Subjects: Denosumab; Dkk-1; Osteoporosis; RANKL; Sclerostin
• ISSN: 8756-3282; 1873-2763
• DOI: 10.1016/j.bone.2019.03.019

The positive effects of denosumab (DMAb) on bone mineral density (BMD) are quickly reversible after its discontinuation. We investigated whether this rebound was associated with dysregulation of the Wnt canonical pathway and/or by the increase in the receptor-activator of nuclear factor-kappa B ligand (RANKL) serum levels. The study included patients (n = 15) with postmenopausal osteoporosis to whom DMAb was administered for 78 months and then discontinued. We collected BMD data at baseline/month 0 (M0), M60, M84 (6 months after last DMAb administration, coinciding when the next DMAb dose would typically be due), and after 3 and 12 months of follow-up (FU-M3 and FU-M12, respectively). Serum C-terminal telopeptide of type 1 collagen (CTX-I), Dickkopf-1 (Dkk-1), and sclerostin were measured at M0, M60, M84, FU-M3, and FU-M12. Serum N-terminal propeptide of type 1 procollagen (PINP) and RANKL were dosed at M60, M84, FU-M3, and FU-12. We found a significant decrease in the T-score at all sites at FU-M12, when compared to M84 (−0.51 ± 0.91 at the lumbar spine; −0.72 ± 0.33 at the total hip; and −0.42 ± 0.27 at the femoral neck, p