Bone metabolism markers are associated with neck circumference in adult Arab women

Albassam, Reem Suliman; Sabico, Shaun; Alnaami, Abdullah M.; Khattak, Malak N. K.; Lei, Kai Y.; Al-Daghri, Nasser M.; Reginster, Jean‐Yves; Alokail, Majed S.

doi:10.1007/s00198-018-04830-6

Cited by 8 publications

(11 citation statements)

References 33 publications

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“…Sclerostin is expressed in cardiovascular tissues (41,42), supporting a potential biological role for this protein in these tissue types. In observational studies, higher concentrations of circulating sclerostin are associated with a higher risk of cardiovascular disease together with increased cardiometabolic risk factors such as hypertension, T2D, and central adiposity (43)(44)(45)(46)(47)(48). In contrast to our genetic findings, these data suggest that lowering of sclerostin may confer protection from cardiovascular disease; however, observational studies also show that osteoporosis and lower BMD are associated with lower sclerostin (49,50), suggesting that increasing sclerostin would lead to higher BMD.…”

Section: Discussioncontrasting

confidence: 90%

Evaluating the cardiovascular safety of sclerostin inhibition using evidence from meta-analysis of clinical trials and human genetics

et al. 2020

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Inhibition of sclerostin is a therapeutic approach to lowering fracture risk in patients with osteoporosis. However, data from phase 3 randomized controlled trials (RCTs) of romosozumab, a first-in-class monoclonal antibody that inhibits sclerostin, suggest an imbalance of serious cardiovascular events, and regulatory agencies have issued marketing authorizations with warnings of cardiovascular disease. Here, we meta-analyze published and unpublished cardiovascular outcome trial data of romosozumab and investigate whether genetic variants that mimic therapeutic inhibition of sclerostin are associated with higher risk of cardiovascular disease. Meta-analysis of up to three RCTs indicated a probable higher risk of cardiovascular events with romosozumab. Scaled to the equivalent dose of romosozumab (210 milligrams per month; 0.09 grams per square centimeter of higher bone mineral density), the SOST genetic variants were associated with lower risk of fracture and osteoporosis (commensurate with the therapeutic effect of romosozumab) and with a higher risk of myocardial infarction and/or coronary revascularization and major adverse cardiovascular events. The same variants were also associated with increased risk of type 2 diabetes mellitus and higher systolic blood pressure and central adiposity. Together, our findings indicate that inhibition of sclerostin may elevate cardiovascular risk, warranting a rigorous evaluation of the cardiovascular safety of romosozumab and other sclerostin inhibitors.

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Section: Discussioncontrasting

confidence: 90%

Evaluating the cardiovascular safety of sclerostin inhibition using evidence from meta-analysis of clinical trials and human genetics

et al. 2020

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“…Total osteocalcin levels . Total osteocalcin levels were reported in 29 studies [ 21 , 53 , 60 , 62 – 65 , 68 , 74 , 76 , 77 , 80 , 81 , 84 , 92 , 97 , 105 , 107 , 119 , 126 , 129 , 135 , 144 , 146 , 147 , 151 , 153 , 166 , 175 ], including 6,332 participants. Obesity was not associated with any difference in osteocalcin levels between individuals with and without obesity ( S7 Fig ), except in studies combining men and women (n = 9: MD = -3.86 ng/ml, 95% CI: -6.78, -0.95, P = 0.009, I 2 = 97%).…”

Section: Resultsmentioning

confidence: 99%

“…Sclerostin levels . Sclerostin levels were reported in 3 studies [ 53 , 57 , 79 ], including 380 participants. In those studies, no difference between individuals with and without obesity was observed.…”

Section: Resultsmentioning

confidence: 99%

Association between obesity and risk of fracture, bone mineral density and bone quality in adults: A systematic review and meta-analysis

et al. 2021

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Background The association between obesity and fracture risk may be skeletal site- and sex-specific but results among studies are inconsistent. Whilst several studies reported higher bone mineral density (BMD) in patients with obesity, altered bone quality could be a major determinant of bone fragility in this population. Objectives This systematic review and meta-analysis aimed to compare, in men, premenopausal women and postmenopausal women with obesity vs. individuals without obesity: 1) the incidence of fractures overall and by site; 2) BMD; and 3) bone quality parameters (circulating bone turnover markers and bone microarchitecture and strength by advanced imaging techniques). Data sources PubMed (MEDLINE), EMBASE, Cochrane Library and Web of Science were searched from inception of databases until the 13th of January 2021. Data synthesis Each outcome was stratified by sex and menopausal status in women. The meta-analysis was performed using a random-effect model with inverse-variance method. The risks of hip and wrist fracture were reduced by 25% (n = 8: RR = 0.75, 95% CI: 0.62, 0.91, P = 0.003, I2 = 95%) and 15% (n = 2 studies: RR = 0.85, 95% CI: 0.81, 0.88), respectively, while ankle fracture risk was increased by 60% (n = 2 studies: RR = 1.60, 95% CI: 1.52, 1.68) in postmenopausal women with obesity compared with those without obesity. In men with obesity, hip fracture risk was decreased by 41% (n = 5 studies: RR = 0.59, 95% CI: 0.44, 0.79). Obesity was associated with increased BMD, better bone microarchitecture and strength, and generally lower or unchanged circulating bone resorption, formation and osteocyte markers. However, heterogeneity among studies was high for most outcomes, and overall quality of evidence was very low to low for all outcomes. Conclusions This meta-analysis highlights areas for future research including the need for site-specific fracture studies, especially in men and premenopausal women, and studies comparing bone microarchitecture between individuals with and without obesity. Systematic review registration number CRD42020159189

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“…Serum intact PTH, osteoprotegerin (OPG), osteopontin (OPN), and receptor activator of nuclear factor- κ B ligand (RANKL) levels were measured using multiplex assay kits (Millipore Corporation, Billerica, MA, USA.) as measured previously [ 20 ]. The intra- and interassay for intact PTH, OPG, and OPN were 10% and 15%, and for RANKL, 5% and 6%.…”

Section: Methodsmentioning

confidence: 99%

PTHR1 Genetic Polymorphisms Are Associated with Osteoporosis among Postmenopausal Arab Women

Abdi

Almiman

Ansari

et al. 2021

BioMed Research International

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The parathyroid hormone 1 receptor (PTHR1) plays a crucial role in calcium homeostasis and bone metabolism. However, its genetic role in regulating bone turnover markers (BTMs) in postmenopausal osteoporosis (PMO) remains unclear. Herein, we explored parathyroid hormone (PTH) and PTHR gene variant susceptibility to osteoporosis and their association with various circulating BTM and inflammatory markers in postmenopausal women of Arab ethnicity. In total, 600 postmenopausal Arab women (300-PMO and 300-control) were genotyped for selected SNPs in PTH (rs1459015, rs307253, rs6054, rs307247, rs10500783 and rs10500784), PTHR1 (rs6442037, rs1138518, and rs724449 SNPs) and PTHR2 (rs9288393, rs10497900, and rs897083). Anthropometrics, BTMs, and inflammatory markers were measured. Bone mineral density (BMD) was measured at the lumbar spine L1–L4 and the femoral neck using dual-energy X-ray absorptiometry (DXA). PTHR1 rs1138518 genotype C/T was found to be a significant risk factor for PMO ( OR = 1.49 , 95% CI 1.0-2.1, P = 0.03 ). The genotypes C/T and T/T of PTHR1 rs1138518 were associated with 25-hydroxy-vitamin D (25(OH)D) regulation. In the PMO group, carriers of the C/T genotype had significantly lower 25(OH)D levels than carriers of the same genotypes in the control group (59.9 (36.7-92.4) nmol/l and 66.4 (43.5-87.8) nmol/l, respectively; P = 0.048 ]. Our study concludes that the PTHR1 rs1138518 genotype could be a potential risk factor for osteoporosis and 25(OH)D regulation in Arab women with PMO.

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Bone metabolism markers are associated with neck circumference in adult Arab women

Cited by 8 publications

References 33 publications

Evaluating the cardiovascular safety of sclerostin inhibition using evidence from meta-analysis of clinical trials and human genetics

Evaluating the cardiovascular safety of sclerostin inhibition using evidence from meta-analysis of clinical trials and human genetics

Association between obesity and risk of fracture, bone mineral density and bone quality in adults: A systematic review and meta-analysis

PTHR1 Genetic Polymorphisms Are Associated with Osteoporosis among Postmenopausal Arab Women

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