Increased Sclerostin Serum Levels Associated with Bone Formation and Resorption Markers in Patients with Immobilization-Induced Bone Loss

Gaudio, Agostino; Pennisi, P.; Bratengeier, Cornelia; Torrisi, Venerando; Lindner, Brigitte; Mangiafico, Roberto Antonio; Pulvirenti, Ivana; Hawa, Gerhard; Tringali, Giovanni; Fiore, Carmelo Erio

doi:10.1210/jc.2010-0067

Cited by 281 publications

(192 citation statements)

References 35 publications

Supporting

Mentioning

162

Contrasting

Unclassified

Order By: Relevance

“…Indeed, we observed an inverse relationship between PA scores and sclerostin levels. This association was also previously reported in immobilized patients, (31) although recent work detected no effects of PA on sclerostin levels among postmenopausal women. (32) Moreover, epidemiological studies demonstrated that PA reduced fracture risk, (33) an observation that might be related to greater improvement in muscle force and coordination, thus contributing to decreased risk of falling and consequently in fewer fractures.…”

Section: Discussionsupporting

confidence: 86%

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

127

View full text Add to dashboard Cite

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

show abstract

Section: Discussionsupporting

confidence: 86%

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

127

View full text Add to dashboard Cite

show abstract

“…Emerging evidence indicates that osteocytes regulate osteoblast function through the inhibitory protein sclerostin (13,16,17); however, osteocytes may also be linked to bone resorption and osteoclastogenesis (29). Sclerostin levels are increased during immobilization and decreases following physical activation (30,31). Our findings of high UCP sclerostin levels are in accordance with the weightless status of the fetus in utero with little strain on the bones despite movements.…”

Section: Discussionsupporting

confidence: 83%

“…Estimation of the effects of a-klotho, FGF23, sclerostin, and 25(OH)D maternal circulating levels at gestational weeks [30][31][32] or UCP levels at birth on BMC was performed by linear regression analyses, with standardized regression coefficients as the effect measures. The unadjusted and adjusted effect estimates were obtained from univariate and multiple regression analyses respectively.…”

Section: Discussionmentioning

confidence: 99%

Umbilical cord levels of sclerostin, placental weight, and birth weight are predictors of total bone mineral content in neonates

Godang

Frøslie

Henriksen

et al. 2013

European Journal of Endocrinology

View full text Add to dashboard Cite

Context: During pregnancy, changes occur in the maternal calcium homeostasis to fulfill fetal demand. We hypothesized that the fibroblast growth factor 23 (FGF23) system and Wnt signaling pathway are important for normal skeletal development in the offspring. Aims: Circulating a-klotho, FGF23, sclerostin, and 25-hydroxyvitamin D (25(OH)D) at the fetal and maternal sides of the placenta were measured to investigate associations with newborn bone mass independent of maternal BMI, calcium and phosphate levels, placental weight, and birth weight. Methods: In a prospective cohort of healthy pregnant women, the total body bone mineral content (BMC) in 202 newborns was measured by dual-energy X-ray absorptiometry. Maternal circulating levels of the biomarkers were measured at gestational weeks 30-32 and in umbilical cord plasma (UCP) at birth. Results: Mean a-klotho and sclerostin concentrations in the UCP were significantly higher than maternal levels (3004 vs 1077 pg/ml; P!0.001 and 629 vs 346 pg/ml; P!0.001 respectively), and mean 25(OH)D was lower (31 vs 45 nmol/l; P!0.001). The UCP and maternal FGF23 levels were similar. No significant effects of maternal biomarkers on BMC were found in regression analyses. Among UCP biomarkers, only UCP sclerostin was significantly associated with BMC in univariate analyses, and the effect remained significant after adjustment for birth weight and other confounders. Conclusions: We found that UCP sclerostin levels, birth weight, and placental weight were significant predictors of neonatal BMC but found no evidence for a main role of maternal levels of a-klotho, FGF23, sclerostin, or 25(OH)D nor of UCP levels of a-klotho, FGF23, or 25(OH)D.

show abstract

“…One possible explanation is that bone nodules do contain a subpopulation of cells with properties similar to osteocytes; consistent with this view, at 15 days of culture, when alkaline phosphatase-positive cells are present in cultures but bone nodules have not yet been formed, SOST expression is undetectable. 8 The increased expression of SOST observed in cultured osteoblasts at 17 weeks after SCI was similar to findings of increased expression of SOST observed in osteocytes in other models of bone unloading (45) and is in general agreement with increased blood levels of sclerostin in immobilized patients (46). These findings suggest that changes in SOST expression are similar across states of bone unloading.…”

Section: Effects Of Sci-and Es-induced Muscle Contraction On Wntsupporting

confidence: 80%

The Central Nervous System (CNS)-independent Anti-bone-resorptive Activity of Muscle Contraction and the Underlying Molecular and Cellular Signatures

Qin

Sun

Cao

et al. 2013

Journal of Biological Chemistry

View full text Add to dashboard Cite

Background: Mechanisms by which muscle regulates bone are poorly understood. Results: Electrically stimulated muscle contraction reversed elevations in bone resorption and increased Wnt signaling in bone-derived cells after spinal cord transection. Conclusion: Muscle contraction reduced resorption of unloaded bone independently of the CNS, through mechanical effects and, potentially, nonmechanical signals (e.g. myokines). Significance: The study provides new insights regarding muscle-bone interactions.

show abstract

Increased Sclerostin Serum Levels Associated with Bone Formation and Resorption Markers in Patients with Immobilization-Induced Bone Loss

Abstract: This study shows for the first time that long-term immobilized patients present hypersclerostinemia associated with reduced bone formation, and suggests that sclerostin could be a link between mechanical unloading and disuse osteoporosis in humans.

Cited by 281 publications

References 35 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

Umbilical cord levels of sclerostin, placental weight, and birth weight are predictors of total bone mineral content in neonates

The Central Nervous System (CNS)-independent Anti-bone-resorptive Activity of Muscle Contraction and the Underlying Molecular and Cellular Signatures

Contact Info

Product

Resources

About