1 3 J Bone Miner Metab DOI 10.1007/s00774-015-0671-5 ORIGINAL ARTICLE Circulating sclerostin and dickkopf-1 levels in ossification of the posterior longitudinal ligament of the spine Masafumi Kashii 1 · Yohei Matuso 1 · Tsuyoshi Sugiura 1 · Takahito Fujimori 1 · Yukitaka Nagamoto 1 · Takahiro Makino 1 · Takashi Kaito 1 · Kosuke Ebina 1 · Motoki Iwasaki 1 · Hideki Yoshikawa 1 Received: 2 October 2014 / Accepted: 8 April 2015 © The Japanese Society for Bone and Mineral Research and Springer Japan 2015 serum sclerostin levels are counterbalanced by underpro- duction of DKK1. Keywords Ossification of posterior longitudinal ligament · Sclerostin · Dickkpf-1 · Wnt/β catenin signal · Diffuse idiopathic spinal hyperostosis Introduction Ossification of the posterior longitudinal ligament (OPLL) of the spine is an intractable disease of unknown etiology [1]. Development of pathological ectopic ossification of the posterior longitudinal ligament induces compression myelopathy or radiculopathy by spinal stenosis and the loss of spinal flexibility by ankylosing spinal hyperostosis [2]. The etiology of OPLL has not been fully clarified [3], but OPLL seems to occur and develop as a result of systemic and local factors in combination with a genetic abnormality [4–7]. Several studies have investigated the relationship between OPLL and bone and mineral metabolism [8–13]. Matsui et al. [8] demonstrated the presence of increased serum pro- collagen type I carboxyl-terminal peptide and intact osteo- calcin in patients with OPLL. Sohn and Chung found that bone mineral density (BMD) in the lumbar spine and femur were higher in persons with OPLL than in control-group members and that rates of osteopenia and osteoporosis were lower in persons with OPLL than in control-group mem- bers [12]. Yoshimura et al. [13] reported that the presence of cervical OPLL showed a significant association between femoral neck BMD and the presence of diffuse idiopathic spinal hyperostosis (DISH) in 1,562 Japanese from a popu- lation-based cohort. Findings from these studies suggest that systemic factors such as constitutional predisposition and Abstract Sclerostin and dickkopf-1(DKK1) are Wnt/β- catenin signal antagonists that play an important role in bone formation. Ossification of the posterior longitudinal ligament (OPLL) of the spine is characterized by patholog- ical ectopic ossification of the posterior longitudinal liga- ment and ankylosing spinal hyperostosis. The aims of this study were to evaluate serum sclerostin and DKK1 levels in persons with OPLL and to identify its relationship with bone metabolism and bone mass in persons with OPLL. This was a case–control study, and 78 patients with OPLL were compared with 39 age- and sex-matched volunteers without OPLL. We analyzed the relationship with calcio- tropic hormones, bone turnover markers, OPLL localiza- tion, number of ossified vertebrae, and bone mineral den- sity of total hip (TH-BMD). Serum sclerostin levels in men with OPLL were significantly higher than in men in the control group (control group: mean = 45.3 pmol/L; OPLL group: mean = 75.7 pmol/L; P = 0.002). Age and scle- rostin levels were positively correlated in men with OPLL (r = 0.43; P = 0.002). Serum sclerostin levels in men with OPLL had a positive correlation with TH-BMD Z-score (r = 0.511; P = 0.011, n = 30). There was a strong nega- tive correlation between serum sclerostin levels and serum DKK1 levels in men with OPLL (r = -0.506; P < 0.001). Bone and mineral metabolism in OPLL differs between men and women. In men with OPLL, systemic secretion of sclerostin increases with advancing age and with higher bone mass. These two Wnt/β-catenin signal antagonists have the opposite effect in persons with OPLL, and higher * Masafumi Kashii mkashii-osk@umin.ac.jp 1 Department of Orthopedic Surgery, Faculty of Medicine, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan