Decreased Plasma Levels of Sclerostin But Not Dickkopf-1 are Associated with an Increased Prevalence of Osteoporotic Fracture and Lower Bone Mineral Density in Postmenopausal Korean Women

Although sclerostin (SOST) and Dickkopf-related protein 1 (DKK1) are major regulators in bone metabolism, their associations with osteoporotic fracture (OF) in Asians are inconclusive. Furthermore, there have been no clinical studies separately considering non-vertebral and vertebral fractures in terms of the blood levels of SOST and DKK1. Among 513 consecutive postmenopausal Korean women, we identified 103 cases defined as subjects with OF (i.e., non-vertebral and/or vertebral fractures). The controls were randomly selected from the remaining 410 subjects and matched 1:1 to cases according to both age and body mass index. Non-vertebral and morphological vertebral fractures were identified by an interviewer-assisted questionnaire and lateral thoracolumbar radiographs, respectively. Bone mineral density (BMD) and plasma levels of SOST and DKK1 were measured. Plasma SOST levels were lower in subjects with OF than in the control group. Each standard deviation decrement of plasma SOST concentration was associated with a multivariable-adjusted odds ratio of 1.77 for any prevalent OF type. The odds for OF was 2.97-fold higher in subjects in the lowest SOST tertile compared with subjects in the highest SOST tertile. These associations remained significant when the non-vertebral and vertebral fractures were analyzed separately. However, prevalent OF was not associated with plasma DKK1 levels, regardless of the type of fracture and the adjustment model employed. Consistently, plasma SOST levels were positively related with BMD values at all measured skeletal sites, although this was not observed for DKK1. Circulating SOST but not DKK1 may be a potential biomarker for predicting bone health in Asians.