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Simulated interventions to ameliorate age-related bone loss indicate the importance of timing

Lookup NU author(s): Dr Carole Proctor

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

Bone remodeling is the continuous process of bone resorption by osteoclasts and bone formation by osteoblasts, in order tomaintain homeostasis. The activity of osteoclasts and osteoblasts is regulated by a network of signaling pathways, including Wnt,parathyroid hormone (PTH), RANKL/OPG and TGF‐β, in response to stimuli such as mechanical loading. During aging there is agradual loss of bone mass due to dysregulation of signaling pathways. This may be due to a decline in physical activity with ageand/or changes in hormones and other signaling molecules. In particular, hormones such as PTH have a circadian rhythm whichmay be disrupted in aging. Due to the complexity of the molecular and cellular networks involved in bone remodeling, severalmathematical models have been proposed to aid understanding of the processes involved. However, to date there are no modelswhich explicitly consider the effects of mechanical loading, the circadian rhythm of PTH and the dynamics of signaling molecules onbone remodeling. Therefore, we have constructed a network model of the system using a modular approach which will allowfurther modifications as required in future research. The model was used to simulate the effects of mechanical loading and also theeffects of different interventions such as continuous or intermittent administration of PTH. Our model predicts that the absence ofregular mechanical loading and/or an impaired PTH circadian rhythm leads to a gradual decrease in bone mass over time whichcan be restored by simulated interventions and that the effectiveness of some interventions may depend on their timing.


Publication metadata

Author(s): Proctor CJ, Gartland A

Publication type: Article

Publication status: Published

Journal: Frontiers in Endocrinology Bone Research

Year: 2016

Volume: 7

Online publication date: 13/06/2016

Acceptance date: 26/05/2016

ISSN (electronic): 1664-2392

Publisher: Frontiers Research Foundation

URL: http://dx.doi.org/10.3389/fendo.2016.00061

DOI: 10.3389/fendo.2016.00061


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