Serum Sclerostin and Risk of Hip Fracture in Older Caucasian Women

Arasu, Aarthi; Cawthon, Peggy M.; Lui, Li‐Yung; P., Thy; Arora, Puneet S.; Cauley, Jane A.; Ensrud, Kristine E.; Cummings, Steven R.

doi:10.1210/jc.2011-3419

Cited by 102 publications

(91 citation statements)

References 20 publications

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“…Fracture risks determined annually remained significant, indicating that risk was maintained over the entire study period. Our study is consistent with the most recent and only report describing higher serum sclerostin levels associated with a greater risk of hip fractures in older women (a case-cohort study of 228 women with incident hip fractures versus 227 women without fracture) (24) but our study contrasts with another recent study by Garnero and colleagues (25) who examined 572 postmenopausal women of the OFELY cohort in which a single measurement of sclerostin levels did not predict the risk of all fractures, although the study may lack statistical power to detect a modest observed association. Such differences are most likely because of differences in the methods used for sclerostin measurement and/or in the selection criteria as well as the mean age of the women examined, together with the size of the population and types of ORFs assessed.…”

Section: Discussionsupporting

confidence: 92%

“…Generally, serum sclerostin levels in our cohort were similar to our reported results, (18) but higher than in reported studies for postmenopausal women. (23,24) This may be explained by differences among women studied in relation to bone mass content, body composition, and/or ethnicity. Also, variations in preanalytical and/or analytical factors (specificity of sclerostin assay) should not be excluded.…”

Section: Discussionmentioning

confidence: 99%

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

Ardawi

Rouzi

Al-Sibiani

et al. 2012

Journal of Bone and Mineral Research

128

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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

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

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

Ardawi

Rouzi

Al-Sibiani

et al. 2012

Journal of Bone and Mineral Research

128

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“…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.…”

Section: Discussionmentioning

confidence: 99%

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

Jean

Chazot

Bresson

et al. 2016

Nephron

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Background: Sclerostin is an osteocyte hormone that decreases osteoblastogenesis. Sclerostin may play a key role in osteoporosis and also in vascular calcification (VC). In chronic kidney disease and haemodialysis (HD) patients, serum sclerostin levels are high. Aim: To assess the correlation of serum sclerostin levels with VC, bone mineral density (BMD), and survival rate in HD patients. Methods: A cross-sectional study was conducted in prevalent HD patients to correlate serum sclerostin tertiles with the Kauppila aortic calcification score, BMD scores and survival rate. Results: We studied 207 patients who had a mean serum sclerostin level of 1.9 ± 0.7 ng/ml. Compared to patients in the 1st tertile of serum sclerostin levels (0.6-1.53 ng/ml), patients in the 3rd tertile (2.2-4.6 ng/ml) were significantly older (73.7 ± 12 vs. 64.7 ± 18 years), more frequently of the male gender (74 vs. 48%), had lower serum bone-specific alkaline phosphatases values (14 ± 9 vs. 20.4 ± 13 µg/l), were less frequently treated with alfacalcidol, displayed lower aortic calcification scores (9.5 ± 5 vs. 12.5 ± 7/24) and had higher BMD scores. Furthermore, patients of the 3rd tertile displayed a lower mortality rate compared to tertile 1 using multivariable adjusted Cox model (hazard ratio 0.5, 95% CI 0.25-0.93, p = 0.03). The main factors associated with VC score were age, diabetes, cardiovascular disease, CRP level and Warfarin use. Conclusion: Our study of HD patients shows that higher serum sclerostin levels are associated with higher BMD, lower aortic calcification scores, and a better survival rate.

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“…Lack of sclerostin leads to profound increases in bone mass in humans (13,18) and in animal models (19), whereas overexpression of sclerostin is associated with decreased mechanical strength in animal models (8). In a recent study, circulating sclerostin levels were positively associated with fracture risk in a large cohort of postmenopausal women (9). Moreover, established determinants of bone strength such as mechanical loading, parathyroid hormone, and estrogen have been shown to modulate the production and/or the secretion of sclerostin (12,20,21).…”

Section: Discussionmentioning

confidence: 99%

“…TZDs have also been recently reported to stimulate sclerostin synthesis in vitro, suggesting an additional mechanism for the detrimental effects of TZDs on bone (6). Sclerostin is a glycoprotein synthesized in bone by osteocytes, which reduces bone formation (7,8), and serum sclerostin levels have been found to be significantly correlated with fracture risk in postmenopausal women (9). Abnormal sclerostin production may contribute to the pathogenesis of bone fragility of patients with T2DM as well as in the actions of TZDs on bone.…”

Section: Introductionmentioning

confidence: 99%

Distinct effects of pioglitazone and metformin on circulating sclerostin and biochemical markers of bone turnover in men with type 2 diabetes mellitus

Lierop

Hamdy

Meer

et al. 2012

European Journal of Endocrinology

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Objective: Patients with type 2 diabetes mellitus (T2DM) have an increased risk of fractures and thiazolidinediones (TZDs) increase this risk. TZDs stimulate the expression of sclerostin, a negative regulator of bone formation, in vitro. Abnormal sclerostin production may, therefore, be involved in the pathogenesis of increased bone fragility in patients with T2DM treated with TZDs. Methods: We measured serum sclerostin, procollagen type 1 amino-terminal propeptide (P1NP), and carboxy-terminal cross-linking telopeptide of type I collagen (CTX) in 71 men with T2DM treated with either pioglitazone (PIO) (30 mg once daily) or metformin (MET) (1000 mg twice daily). Baseline values of sclerostin and P1NP were compared with those of 30 healthy male controls. Results: Compared with healthy controls, patients with T2DM had significantly higher serum sclerostin levels (59.9 vs 45.2 pg/ml, P!0.001) but similar serum P1NP levels (33.6 vs 36.0 ng/ml, PZ0.39). After 24 weeks of treatment, serum sclerostin levels increased by 11% in PIO-treated patients and decreased by 1.8% in MET-treated patients (PZ0.018). Changes in serum sclerostin were significantly correlated with changes in serum CTX in all patients (rZ0.36, PZ0.002) and in PIO-treated patients (rZ0.39, PZ0.020), but not in MET-treated patients (rZ0.17, PZ0.31). Conclusions: Men with T2DM have higher serum sclerostin levels than healthy controls, and these levels further increase after treatment with PIO, which is also associated with increased serum CTX. These findings suggest that increased sclerostin production may be involved in the pathogenesis of increased skeletal fragility in patients with T2DM in general and may specifically contribute to the detrimental effect of TZDs on bone.

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Serum Sclerostin and Risk of Hip Fracture in Older Caucasian Women

Abstract: We conclude that higher serum sclerostin levels are associated with a greater risk of hip fractures in older women. In addition, the risk of hip fracture is amplified when high sclerostin levels are combined with lower BMD.

Cited by 102 publications

References 20 publications

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

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

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

Distinct effects of pioglitazone and metformin on circulating sclerostin and biochemical markers of bone turnover in men with type 2 diabetes mellitus

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