High serum sclerostin predicts the occurrence of osteoporotic fractures in postmenopausal women: The center of excellence for osteoporosis research study

Abstract

Sclerostin regulates bone formation by inhibiting Wnt pathway signaling. Low circulating sclerostin levels cause high bone mass. We hypothesized that postmenopausal women with increased sclerostin levels have a greater risk for osteoporosis-related fractures. We examined the association between circulating sclerostin together with bone turnover markers and osteoporosis-related fracture risk in 707 postmenopausal women, in a population-based study with a mean follow-up period of 5.2 AE 1.3 years. Multivariate Cox proportional hazards regression models were used to analyze fracture risk, adjusted for age, body mass index, and other confounding risk factors. High sclerostin levels were strongly associated with increased fracture risk. After adjustment for age and other confounders, the relative fracture risk was more than sevenfold among postmenopausal women for each 1-SD increment increase in sclerostin level. Women in the highest quartile of sclerostin levels had about a 15-fold increase in fracture risk. Results were similar when we compared sclerostin at the 1-year visit to an average of two to three annual measurements. Fracture risk attributable to sclerostin levels was 56.6% in the highest quartile. Only high levels of bone resorption markers (plasma cross-linked C-terminal telopeptide of type 1 collagen [p-CTx], urinary CTx [u-CTx], and urinary N-telopeptide of type 1 collagen [u-NTx]) were predictive of osteoporosis-related fractures but at much lower hazard ratio (HR) values than that of serum sclerostin. Associations between sclerostin levels and fracture risk were independent of bone mineral density and other confounding risk factors. High sclerostin levels are a strong and independent risk factor for osteoporosis-related fractures among postmenopausal women. ß

Gender differences in sclerostin and clinical characteristics in type 1 diabetes mellitus

“…The latter is consistent with the data reported by Gennari et al (16) using DXA, although an association between sclerostin serum levels and DXA measurements was also described in T1DM (17). Besides BMD, in previous works, sclerostin was associated with fracture risk, although etherogeneus results were reported (31,32). In particular, sclerostin was related to vertebral fractures in T2DM (33).…”

“…A reduced bone formation as a consequence of reduced osteoblast activity has been identified as the mean pathogenetic effect or for low bone mineral density (BMD) in subjects with T1DM (1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39). intimal thickening in atherosclerosis, and Wnt/b-catenin signaling is a regulator of VSMC behavior (9).…”

SOST Polymorphisms and Response to Alendronate Treatment in Postmenopausal Chinese Women With Osteoporosis

“…SOST has been revealed as a susceptibility gene for osteoporosis and osteoporotic fractures in different populations, including in Chinese [19,20,31,32]. Moreover, a positive correlation has been reported between incident hip fractures and high sclerostin levels [33,34]. In this study, we also find genetic variance of SOST is correlated to skeletal response to alendronate treatment for the first time.…”

High Serum Sclerostin Levels Are Associated with a Better Outcome in Haemodialysis Patients

“…This could be in apparent contradiction with the known impact of sclerostin on post-menopausal osteoporosis [30]. Hence, in post-menopausal women, high serum sclerostin levels predict osteoporotic fractures more than other bone makers [31,32]. Besides, Malluche et al [33] reported that baseline serum sclerostin level correlated with bone mass, but 1-year follow-up showed that high serum sclerostin predicts the loss of more bone mass.…”