Dataset Information

GWAS for Genetic Determinants of Bone Fragility

ABSTRACT:

Osteoporotic fractures are largely due to an increased propensity to fall with aging and a reduction in bone strength. Although skeletal architecture contributes to fracture risk, bone mineral density (BMD) is the most important determinant of bone strength and fracture risk. Between 60 and 80% of the variance of BMD of adult Caucasian women is due to heritable factors. Final BMD is a function of peak bone mass attained during young adulthood and the subsequent rate of bone loss, which occurs as a result of both post-menopausal estrogen loss and aging. The evidence for a genetic contribution to rate of loss in BMD is substantially weaker than that for peak BMD. Therefore, we have focused our sample collection on the recruitment of premenopausal women, in whom we have sought to identify the genes influencing peak BMD at the spine and hip, the two major skeletal sites of osteoporotic fracture.

The primary goal of this study is to identify genes that affect peak BMD in premenopausal women. Identification of these genes may: 1) lead to molecular tests that predict risk of osteoporosis and allow institution of early preventive measures; 2) provide insight into basic bone cell biology and other factors that affect peak BMD; and 3) provide molecular targets for therapeutic agents to increase BMD.

PROVIDER: phs000138 | dbGaP |

SECONDARY ACCESSION(S): PRJNA75699PRJNA75697

REPOSITORIES: dbGaP

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Dataset's files

Source:

			Action	DRS
	Study_Report.phs000138.CIDR_BoneFragility.v1.p1.MULTI.pdf	Pdf
	manifest_phs000138.CIDR_BoneFragility.v1.p1.c1.GRU.pdf	Pdf
	datadict_v2.xsl	Other
	phs000138.v1.pht000617.v1.Bone_Fragility_Data.data_dict_2009_08_03.xml	Xml
	phs000138.v1.pht000617.v1.p1.Bone_Fragility_Data.var_report_2009_08_03.xml	Xml

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Project description:Proctor2016 - Circadian rhythm of PTH and the dynamics of signaling molecules on bone remodeling This model is described in the article: Simulated Interventions to Ameliorate Age-Related Bone Loss Indicate the Importance of Timing. Proctor CJ, Gartland A. Front Endocrinol (Lausanne) 2016; 7: 61 Abstract: Bone remodeling is the continuous process of bone resorption by osteoclasts and bone formation by osteoblasts, in order to maintain homeostasis. The activity of osteoclasts and osteoblasts is regulated by a network of signaling pathways, including Wnt, parathyroid hormone (PTH), RANK ligand/osteoprotegrin, and TGF-?, in response to stimuli, such as mechanical loading. During aging there is a gradual loss of bone mass due to dysregulation of signaling pathways. This may be due to a decline in physical activity with age and/or changes in hormones and other signaling molecules. In particular, hormones, such as PTH, have a circadian rhythm, which may be disrupted in aging. Due to the complexity of the molecular and cellular networks involved in bone remodeling, several mathematical models have been proposed to aid understanding of the processes involved. However, to date, there are no models, which explicitly consider the effects of mechanical loading, the circadian rhythm of PTH, and the dynamics of signaling molecules on bone remodeling. Therefore, we have constructed a network model of the system using a modular approach, which will allow further modifications as required in future research. The model was used to simulate the effects of mechanical loading and also the effects of different interventions, such as continuous or intermittent administration of PTH. Our model predicts that the absence of regular mechanical loading and/or an impaired PTH circadian rhythm leads to a gradual decrease in bone mass over time, which can be restored by simulated interventions and that the effectiveness of some interventions may depend on their timing. This model is hosted on BioModels Database and identified by: BIOMD0000000612. To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.

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GWAS for Genetic Determinants of Bone Fragility

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