title: Increased serum sclerostin and decreased serum IGF-1 are associated with vertebral fractures among postmenopausal women with type-2 diabetes.
abstract: Insulin-like growth factor 1 (IGF-1) is a determinant of bone mass and is inversely associated with vertebral fractures (VFs). Sclerostin regulates bone formation by inhibiting Wnt/β-catenin signaling. Currently, there is little information on circulating sclerostin levels among postmenopausal women with type-2 diabetes mellitus (T2DM) with VFs in relation to serum IGF-1 (s-IGF-1). We investigated the relationships between serum sclerostin, s-IGF-1, and VFs in postmenopausal women with T2DM. We assessed cross-sectionally 482 postmenopausal women with T2DM and 482 age-matched postmenopausal women without T2DM who were recruited at diabetic clinics and primary health care centers for inclusion in a bone health survey. The main outcome measures were serum sclerostin, s-IGF-1, bone mineral density (BMD), and bone turnover markers. Lateral X-rays of the thoracic and lumbar spine were taken to diagnose VFs. Serum sclerostin levels were increased, whereas s-IGF-1 levels were decreased when T2DM women were stratified by the number of VFs (P<0.0001). Multiple logistic regression analysis showed that serum sclerostin levels were positively associated with 1 VF (odds ratio [OR]=1.27, (95% CI:1.01-2.03), P=0.016), 2 VFs (OR=1.41, (95% CI:1.03-2.36), P=0.006), and ≥3 VFs (OR=1.54, (95% CI:1.12-2.44) P=0.005). s-IGF-1 levels were inversely associated with 1 VF (OR=0.58, (95% CI:0.39-0.88), P=0.041), 2 VFs (OR=0.42, (95% CI:0.21-0.90), P=0.012), and ≥3 VFs (OR=0.19, (95% CI: 0.14-0.27), P<0.001). Increased serum sclerostin and decreased s-IGF-1 were associated with VFs among postmenopausal women with T2DM, suggesting that sclerostin and/or IGF-1 may be involved in increased bone fragility in T2DM and could be potential markers of VF severity.
authors.affiliation: Center of Excellence for Osteoporosis Research, Faculty of Medicine and King Abdulaziz University Hospital, King Abdulaziz University, Jeddah, Saudi Arabia. msmardawi@yahoo.com
authors.forename: Mohammed-Salleh M
authors.initials: MS
authors.lastname: Ardawi
authors.forename: Daad H
authors.initials: DH
authors.lastname: Akhbar
authors.forename: Abdulrahman
authors.initials: A
authors.lastname: Alshaikh
authors.forename: Maimoona M
authors.initials: MM
authors.lastname: Ahmed
authors.forename: Mohammed H
authors.initials: MH
authors.lastname: Qari
authors.forename: Abdulrahim A
authors.initials: AA
authors.lastname: Rouzi
authors.forename: Ahmed Y
authors.initials: AY
authors.lastname: Ali
authors.forename: Adel A
authors.initials: AA
authors.lastname: Abdulrafee
authors.forename: Mamdouh Y
authors.initials: MY
authors.lastname: Saeda
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000368:Aged; D015519:Bone Density / Q000502:physiology; D019485:Bone Morphogenetic Proteins / Q000097:blood*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000503:physiopathology*; D005260:Female; D005819:Genetic Markers; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008875:Middle Aged; D017698:Postmenopause; D016103:Spinal Fractures / Q000097:blood*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D019485:Bone Morphogenetic Proteins; D005819:Genetic Markers; C422903:SOST protein, human; D007334:Insulin-Like Growth Factor I
keywords: Bone turnover markers; Diabetes; IGF-1; Postmenopausal women; Sclerostin