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Oxidative stress and bone mineral density in elderly men: antioxidant activity of alpha-tocopherol
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , UCR-Uppsala Clinical Research center.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , UCR-Uppsala Clinical Research center.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Oxidative Stress and Inflammation.
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2009 (English)In: Free Radical Biology & Medicine, ISSN 0891-5849, E-ISSN 1873-4596, Vol. 47, no 5, p. 668-673Article in journal, Letter (Refereed) Published
Abstract [en]

Oxidative stress has recently been identified as a pivotal pathogenetic factor of bone loss in mice, but its importance in humans is not clear. We aimed to investigate the association between urinary 8-iso-PGF(2 alpha) levels, a major F(2)-isoprostane and a reliable in vivo biomarker of oxidative stress, and bone mineral density (BMD), and to study whether vitamin E in the form of serum alpha-tocopherol, a scavenger of peroxyl radicals, modifies the association. In 405 men, urinary 8-iso-PGF(2 alpha) and serum alpha-tocopherol were measured at age 77 years and BMD at age 82 years. One SD increase in 8-iso-PGF(2 alpha) corresponded to an approximately 2-4% decrease in average adjusted BMD values of total body, lumbar spine, and proximal femur (all P<0.001). Serum alpha-tocopherol levels seemed to modify the association between urinary 8-iso-PGF(2 alpha) and BMD. Men with alpha-tocopherol levels below the median combined with high oxidative stress, i.e., 8-iso-PGF(2 alpha) above the median, had 7% (95% CI 3-11%) lower BMD at the lumbar spine and 5% (95% CI 2-9%) lower BMD at the proximal femur. In elderly men high oxidative stress is associated with reduced BMD, which is more pronounced in individuals with low serum levels of the antioxidant vitamin E.

Place, publisher, year, edition, pages
2009. Vol. 47, no 5, p. 668-673
Keywords [en]
BMD, Bone, Isoprostanes, Prostaglandins, Osteoporosis, Vitamin E, α-Tocopherol
National Category
Surgery
Research subject
Orthopaedics
Identifiers
URN: urn:nbn:se:uu:diva-109406DOI: 10.1016/j.freeradbiomed.2009.05.031ISI: 000268995900024PubMedID: 19500667OAI: oai:DiVA.org:uu-109406DiVA, id: diva2:272367
Available from: 2009-10-15 Created: 2009-10-15 Last updated: 2017-12-12Bibliographically approved
In thesis
1. Influence of Oxidative Stress on Muscle and Bone
Open this publication in new window or tab >>Influence of Oxidative Stress on Muscle and Bone
2009 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Reactive oxygen species (ROS) induce oxidative stress and although are primarily recognized for playing a deleterious biological role, they can be beneficial to cell systems. ROS are extremely short-lived and normally tightly regulated by antioxidant defence systems. Cells react to oxidative stress in different ways, which primarily depends on cell type, stress severity, or both. There is a general limitation in extrapolating to humans conclusions drawn from in vitro and animal studies because of important species-specific differences. Therefore, the general aim of this thesis was to study the influence of oxidative stress on human muscle and bone in vivo.

In paper I we presented a one-step HPLC method optimized for the simultaneous determination of purine degradation products in small microdialysis samples. The clinical utility of the method was successfully tested in a patient with traumatic brain injury. In paper II we evaluated microdialysis as an in vivo method to characterize the relative kinetics of ROS-related metabolites in human skeletal muscle exposed to ischaemia-reperfusion. Results indicated that microdialysis was feasible and safe to use in monitoring metabolic events during tourniquet-assisted surgery. In paper III we investigated the association between an oxidative stress marker (urinary 8-iso-PGF) and bone mineral density (BMD) and whether α-tocopherol modified the association. The main finding was the negative association between 8-iso-PGF and BMD and that the association was further dependent on serum α-tocopherol level. In paper IV we performed a randomized controlled trial to evaluate the influence of Q10 supplementation on exercise performance and metabolites of muscular damage. We did not observe any effects on exercise capacity after 8 weeks of Q10 administration. Nor did we find a significant effect on serum markers related to oxidative stress.

In conclusion we have studied the influence of oxidative stress on muscle and bone in vivo in humans. The oxidative stress was triggered by four different causes (trauma, ischemia-reperfusion, ageing, and exercise exhaustion).

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2009. p. 72
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 501
Keywords
bone mineral density, coenzyme Q10, exercise, ischaemia, isprostanes, muscle, oxidative stress, oxygen radicals, reperfusion, tocopherol
National Category
Surgery
Research subject
Orthopaedics
Identifiers
urn:nbn:se:uu:diva-110093 (URN)978-91-554-7661-8 (ISBN)
Public defence
2009-12-17, Rosénsalen, Barnkliniken, Akademiska sjukhuset, Uppsala, 13:00 (Swedish)
Opponent
Supervisors
Available from: 2009-11-25 Created: 2009-11-03 Last updated: 2009-11-25Bibliographically approved

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