Background: Although sclerostin (SOST) and Dickkopf-related protein 1 (DKK1) are major regulators in bone metabolism, the associations between these soluble Wnt antagonists and osteoporotic fracture (OF) in Asians, who may have distinct biologic characteristics with Caucasians, 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.
Methods: This is a casecontrol study in postmenopausal Korean women. Among 513 consecutive subjects not taking any drug or having any disease that could affect bone metabolism, 105 cases having any kind of OF (i.e., non-vertebral and/or vertebral fractures) and age- and BMI-matched 105 controls were enrolled. Non-vertebral (i.e., wrist, forearm, humerus, hip, and pelvis) 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 also measured.
Results: Plasma SOST was markedly lower in subjects with OF than their controls. Each S.D. decrement of plasma SOST concentration associated with a multivariable-adjusted odds ratio of 1.75 for any kind of prevalent OF. The odds for OF was 2.79-fold higher in subjects in the lowest SOST tertile compared with those in the highest SOST tertile. Importantly, all these associations were still significant when the non-vertebral and vertebral fractures were analyzed separately. However, prevalent OF did not associate with plasma DKK1 levels regardless of the fracture type and the adjustment model that was employed. Consistently, plasma SOST levels, but not DKK1, related positively with BMD values at all measured skeletal sites.
Conclusions: Circulating SOST but not DKK1 could be a potential biomarker for predicting bone health in Asian populations.