dc.creator | Ruiz Lozano, Rocío | es |
dc.creator | Calvo Gallego, José Luis | es |
dc.creator | Pivonka, Peter | es |
dc.creator | McDonald, Michele M. | es |
dc.creator | Martínez Reina, Francisco Javier | es |
dc.date.accessioned | 2024-06-18T09:22:13Z | |
dc.date.available | 2024-06-18T09:22:13Z | |
dc.date.issued | 2024 | |
dc.identifier.citation | Ruiz-Lozano, R., Calvo-Gallego, J.L., Pivonka, P., McDonald, M.M. y Martínez-Reina, F.J. (2024). An in silico approach to elucidate the pathways leading to primary osteoporosis: age‑related vs. postmenopausal. Biomechanics and Modeling in Mechanobiology. https://doi.org/10.1007/s10237-024-01846-2. | |
dc.identifier.issn | 1617-7959 | es |
dc.identifier.issn | 1617-7940 | es |
dc.identifier.uri | https://hdl.handle.net/11441/160606 | |
dc.description | This article is licensed under a Creative Commons Attribution 4.0 International License. | es |
dc.description.abstract | Numerical models of bone remodelling have traditionally been used to perform in silico tests of bone loss in postmenopausal
women and also to simulate the response to different drug treatments. These models simulate the menopausal oestrogen
decline by altering certain signalling pathways. However, they do not consider the simultaneous effect that ageing can have
on cell function and bone remodelling, and thus on bone loss. Considering ageing and oestrogen decline together is important
for designing osteoporosis treatments that can selectively counteract one or the other disease mechanism. A previously devel-
oped bone cell population model was adapted to consider the effect of ageing through: (1) the decrease of TGF-β contained
in the bone matrix and (2) an increased production of sclerostin by non-skeletal cells. Oestrogen deficiency is simulated
in three different ways: (a) an increase in RANKL expression, (b) a decrease in OPG production, and (c) an increase in
the responsiveness of osteoclasts to RANKL. The effect of ageing was validated using the cross-sectional study of (Riggs
et al. in J Bone Miner Res 19: 1945-1954, 2004) on BMD of trabecular bone of the vertebral body of men. The joint effect
of ageing and oestrogen deficiency was validated using these same clinical results but in women. In ageing, the effect of
the increasing production of sclerostin is more important than the decrease of TGF-β , while the three mechanisms used to
simulate the effect of oestrogen deficiency produce almost identical responses. The results show that an early menopause
leads to a lower average density in the fifth decade, but after the sixth decade the average density is independent of the age
at menopause. Treatment of osteoporosis with denosumab was also simulated to conclude that the drug is not very effective
if started before 10 years after menopause or before age 60. | es |
dc.format | application/pdf | es |
dc.format.extent | 17 p. | es |
dc.language.iso | eng | es |
dc.publisher | Springer | es |
dc.relation.ispartof | Biomechanics and Modeling in Mechanobiology. | |
dc.rights | Atribución 4.0 Internacional | * |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | * |
dc.subject | Age-related osteoporosis | es |
dc.subject | Postmenopausal osteoporosis | es |
dc.subject | RANKL-RANK-OPG signalling pathway | es |
dc.subject | Oestrogen deficiency | es |
dc.subject | TGF-β | es |
dc.title | An in silico approach to elucidate the pathways leading to primary osteoporosis: age‑related vs. postmenopausal | es |
dc.type | info:eu-repo/semantics/article | es |
dc.type.version | info:eu-repo/semantics/publishedVersion | es |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | es |
dc.contributor.affiliation | Universidad de Sevilla. Departamento de Ingeniería Mecánica y de Fabricación | es |
dc.relation.projectID | PID2019-106969RB-I00 | es |
dc.relation.projectID | IC190100020 | es |
dc.relation.publisherversion | https://link.springer.com/article/10.1007/s10237-024-01846-2 | es |
dc.identifier.doi | 10.1007/s10237-024-01846-2 | es |
dc.contributor.group | Universidad de Sevilla. TEP111: Ingeniería Mecánica | es |
dc.journaltitle | Biomechanics and Modeling in Mechanobiology | es |
dc.contributor.funder | Ministerio de Ciencia, Innovación y Universidades (MICINN). España | es |
dc.contributor.funder | Australian Research Council | es |