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High dietary intake of retinol leads to bone marrow hypoxia and diaphyseal endosteal mineralization in rats
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Pharmacology. (Clinical pharmacogenetics and osteoporosis)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine. (Eva Vingård)ORCID iD: 0000-0002-8949-3555
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Pharmacology. (Clinical pharmacogenetics and osteoporosis)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Pharmacology. (Clinical pharmacogenetics and osteoporosis)
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2011 (English)In: Bone, ISSN 8756-3282, E-ISSN 1873-2763, Vol. 48, no 3, 496-506 p.Article in journal (Refereed) Published
Abstract [en]

Vitamin A (retinol) is the only molecule known to induce spontaneous fractures in laboratory animals and we have identified retinol as a risk factor for fracture in humans. Since subsequent observational studies in humans and old animal data both show that high retinol intake appears to only have small effects on bone mineral density (BMD) we undertook a mechanistic study of how excess retinol reduces bone diameter while leaving BMD essentially unaffected. We fed growing rats high doses of retinol for only 1week. Bone analysis involved antibody-based methods, histology, pQCT, biomechanics and bone compartment-specific PCR together with Fourier Transform Infrared Spectroscopy of bone mineral. Excess dietary retinol induced weakening of bones with little apparent effect on BMD. Periosteal osteoclasts increased but unexpectedly endosteal osteoclasts disappeared and there was a reduction of osteoclastic serum markers. There was also a lack of capillary erythrocytes, endothelial cells and serum retinol transport protein in the endosteal/marrow compartment. A further indication of reduced endosteal/marrow blood flow was the increased expression of hypoxia-associated genes. Also, in contrast to the inhibitory effects in vitro, the marrow of retinol-treated rats showed increased expression of osteogenic genes. Finally, we show that hypervitaminotic bones have a higher degree of mineralization, which is in line with biomechanical data of preserved stiffness in spite of thinner bones. Together these novel findings suggest that a rapid primary effect of excess retinol on bone tissue is the impairment of endosteal/marrow blood flow leading to hypoxia and pathological endosteal mineralization.

Place, publisher, year, edition, pages
2011. Vol. 48, no 3, 496-506 p.
Keyword [en]
Bone mineralization, Nutrition, Osteoporosis, Retinol, Rodent
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-133794DOI: 10.1016/j.bone.2010.10.169ISI: 000288773800010PubMedID: 21035577OAI: oai:DiVA.org:uu-133794DiVA: diva2:370386
Note

Correction in: Bone, vol. 50, issue 5, pages 1205.

DOI: 10.1016/j.bone.2012.02.016

Available from: 2010-11-16 Created: 2010-11-16 Last updated: 2017-05-03Bibliographically approved

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Lind, ThomasLind, MonicaJacobson, AnnicaLarsson, SuneMelhus, Håkan

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